Degree Of Tissue Differentiation Research Articles

Expression, Characteristics, and Clinical Target Prediction of PIK3C3/ vps34 in Gastric Cancer.

This study aimed to investigate the expression pattern of phosphatidylinositol 3-kinase class III (PIK3C3/vps34) in gastric cancer (GC) tissues and their juxtaposed normal counterparts and its correlation with the clinicopathological attributes and prognostic outlook of afflicted individuals. Immunohistochemical (IHC) staining was used to ascertain the expression levels of PIK3C3/vps34 across 60 GC tissues juxtaposed with their normal counterparts. Statistical methodologies were used to scrutinize the correlation between PIK3C3/vps34 expression and clinicopathological features, along with prognostic implications for GC patients. In GC tissues, the positive expression rate of PIK3C3/vps34 was 23.3% (14/60), which contrasted sharply with the markedly elevated rate of 66.7% (40/60) observed in adjacent tissues. The positive expression proportion of PIK3C3/vps34 within GC tissues exhibited a notable decrease than in adjacent tissues (P<0.05). The expression of PIK3C3/vps34 inverse-ly correlated with tumor size, degree of tissue differentiation, depth of tumor infiltration, and incidence of lymph node metastasis (P<0.05), whereas no significant associations were found with patient sex, age, tumor location, TNM staging, or distant metastasis (P > 0.05). As the tumor diameter increases, the degree of tissue differentiation diminishes, tumor infiltration depth intensifies, lymph node metastasis emerges, the TNM stage progresses, and PIK3C3/vps34 expression level within GC tissues declines correspondingly. Kaplan-Meier survival analysis unveiled a prolonged survival duration among GC patients exhibiting heightened PIK3C3/vps34 expression than in their counterparts with diminished expression (HR=0.66, 95% CI: 0.55-0.80), demonstrating statistical significance (P<0.05). Protein interaction analysis revealed noteworthy interactions involving PIK3C3 with Beclin 1, UVRAG, and ATG14. PIK3C3/vps34 is downregulated in GC tissues, exerting a pivotal role in tumorigenesis, and is intimately linked with the prognostic trajectory of GC patients. It may serve as a significant biomarker for prognostic evaluation and a promising molecular therapeutic target for GC.

Exploring the Expression and Prognosis of Mismatch Repair Proteins and PD-L1 in Colorectal Cancer in a Chinese Cohort.

Exploring the expression and prognosis of mismatch repair proteins and PD-L1 in colorectal cancer. A total of 272 patients with surgically resected CRC were enrolled in the study from January 2018 to May 2022 at Nanjing Drum Tower Hospital (The Affiliated Hospital of Nanjing University Medical School). Surgically resected samples were collected from patients along with general, clinicopathological, and imaging data for each patient. Immunohistochemistry (IHC) was used to detect expression of MSH2, MSH6, MLH1, and PMS2 proteins in tumor tissue. X-squared (X2) testing was performed to investigate the correlation between expression of MMR proteins and PD-L1 in CRC tumor tissues and clinicopathological characteristics. Correlation analysis was also used to compare the deletion of four MMR proteins in CRC tumor tissues. A survival curve and Log rank test were used to investigate the relationship between the expression of MMR proteins and PD-L1 with regard to CRC patient prognosis and survival. MMR protein expression deletion was correlated with tumor location, the degree of tissue differentiation, and TNM stage (P<0.05). PD-L1 expression was correlated with TNM stage (P<0.05). Correlation analysis of deletion of MMR protein isoform expression found that PMS2 deletion was significantly correlated with MLH1 deletion (P<0.05). Similarly, MSH2 deletion was significantly correlated with MSH6 deletion (P<0.05). PMS2 deletion was also found to be correlated with PD-L1 expression (P<0.05). Progression-free survival was found to be significantly longer in mismatch repair-proficient (pMMR) patients compared with mismatch repair-deficient (dMMR) patients. Deletion of MMR proteins and expression of PD-L1 are closely related to clinicopathological characteristics and overall prognosis of CRC patients. This suggests the relevance of MMR and PD-L1 as potential biomarkers for treatment of CRC patients.

Expression and clinical significance of plasma methylated SEPT 9 gene in patients with primary liver cancer

Objective: To investigate the expression and clinical significance of plasma methylated SEPT9 (mSEPT9) gene in patients with primary liver cancer. Methods: 393 cases who visited our hospital from May 2016 to October 2018 were selected. Among them, 75 cases were in the primary liver cancer (PLC) group, 50 cases were in the liver cirrhosis (LC) group, and 268 cases were in the healthy control group (HC). The three groups' positive rates of mSEPT9 expression in the peripheral plasma were detected by the polymerase chain reaction (PCR) fluorescent probe method. The correlational clinical features of liver cancer were analyzed. At the same time, the electrochemiluminescence detection method was used to compare the AFP positive rate. Statistical analysis was conducted using chi-square tests or continuity-corrected chi-square tests. Results: 367 cases actually had valid samples. There were 64, 42, and 64 cases in the liver cancer group, cirrhosis group, and healthy control group, respectively. Among them, 34 cases of liver cancer were verified from pathological tissues. The positive rate of plasma mSEPT9 was significantly higher in the liver cancer group than that in the liver cirrhosis and healthy control groups [76.6% (49/64), 35.7% (15/42), and 3.8% (10/261), respectively], and the differences were statistically significant (χ (2) = 176.017, P < 0.001). The sensitivity of plasma mSEPT9 detection (76.6%) was significantly better in liver cancer (76.6%) than that of AFP patients (54.7%), and the difference was statistically significant (χ (2) = 6.788, P < 0.01). Compared with the single detection, the sensitivity and specificity of plasma mSEPT9 combined with AFP were significantly improved (89.7% vs. 96.3%, respectively). Patients with liver cancer aged≥50 years, with clinical stage II or above, and those with pathological signs of moderate to low differentiation had higher levels of plasma mSEPT9 positive expression, and the differences were statistically significant (χ (2) = 6.41, 9.279, 6.332, P < 0.05). During the follow-up period, the survival time of liver cancer patients with positive plasma mSEPT9 expression was significantly shorter than that of those with negative expression (310 ± 26 days vs. 487 ± 59 days, respectively), with statistically significant differences (Log Rank P = 0.039). Conclusion: In China, the positive rate of plasma mSEPT9 detection in liver cancer patients is higher than that of AFP in relation to age, clinical stage, and degree of tissue differentiation; additionally, it has certain survival predictive values. As a result, detecting this gene has important clinical significance and potential clinical application value in the non-invasive diagnosis and prognosis assessment of patients with primary liver cancer.

To investigate the prognostic factors of stage Ⅰ-Ⅱ gastric cancer based on P53 mutation and tumor budding.

P53 is a tumor suppressor and genome guardian factor, and tumor budding is a key link in tumor metastasis. The purpose of this study was to investigate P53 mutation and tumor budding in stage Ⅰ-Ⅱ gastric cancer, to explore the correlation with clinicopathological features, and to reveal the independent prognostic factors of gastric cancer. The data of 588 patients with stage Ⅰ-Ⅱ gastric cancer who underwent radical surgical resection from April 2015 to December 2016 in the Fourth Hospital of Hebei Medical University were retrospectively analyzed and followed up. Immunohistochemistry Envision method was used to conduct P53 staining for paraffin-embedded gastric cancer tissues, and ITBCC recommended tumor budding evaluation method was used to count tumor budding in gastric cancer tissues. The factors affecting the prognosis of gastric cancer were analyzed. There were 209 cases (35.54%) of P53 wild-type and 379 cases (64.46%) of P53 mutant in 588 patients with stage Ⅰ-Ⅱ gastric cancer. P53 mutation rate were closely correlated with Lauren classification (χ2 =8.152, p=0.017), degree of differentiation (χ2 =10.495, p=0.004), number of lymph node metastasis (χ2 =25.550, p<0.001), and clinical stage (χ2 =7.617, p=0.016). Tumor budding were closely correlated with Lauren classification (χ2 =194.533, p<0.001), degree of tissue differentiation (χ2 =22.719, p<0.001), depth of tumor invasion (χ2 =19.204, p=0.004), number of lymph node metastasis (χ2 =22.555, p=0.001), clinical stage (χ2 =10.769, p=0.005), and vascular tumors bolt (χ2 =12.478, p=0.002). The higher the tumor budding grade was, the higher the P53 mutation rate was (χ2 =12.933, p=0.002). Lauren classification (p<0.001), degree of tissue differentiation (p=0.005), vascular tumors bolt (p<0.001) and P53 mutation (p=0.006) were independent influencing factors for 5-year survival of patients with stage Ⅰ-Ⅱ gastric cancer. P53 mutation status is an independent prognostic factor for gastric cancer patients and a promising cancer treatment target. Tumor budding is a very reliable independent prognostic parameter with important clinical value and should be routinely reported as a biomarker.

Establishment and Validation of a Nomogram Prognostic Model for Epithelioid Hemangioendothelioma.

Background Epithelioid hemangioendothelioma (EHE) is an ultrarare vascular sarcoma. At present, the epidemiological and clinical characteristics and prognostic factors are still unclear. Our study attempted to describe clinical features, investigate the prognostic indicators, and establish the nomogram prediction model based on the Surveillance, Epidemiology, and End Results (SEER) database for EHE patients. Methods The patients diagnosed with EHE from 1986 to 2018 were collected from the SEER database and were randomly divided into a training group and a validation group at a ratio of 7 : 3. The Cox proportional hazard models were used to determine the independent factors affecting prognosis and establish a nomogram prognostic model to predict the survival rates for patients with EHE. The accuracy and discriminative ability of the model were measured using the concordance index, receiver operating characteristic curves, and calibration curves. The clinical applicability and application value of the model were evaluated by decision curve analysis. Results The overall age-adjusted incidence of EHE was 0.31 patients per 1,000,000 individuals, with a statistically significant difference per year. Overall survival at 1, 5, and 10 years for all patients was 76.5%, 57.4%, and 48.2%, respectively. Multivariate Cox regression analysis identified age, tumour stage, degree of tissue differentiation, surgical treatment, chemotherapy, and radiotherapy as independent factors affecting prognosis (P < 0.05). The C-index values for our nomogram model of training group and validation group were 0.752 and 0.753, respectively. The calibration curve was in good agreement with the actual observation results, suggesting that the prediction model has good accuracy. The decision curve analysis indicated a relatively large net benefit. Conclusions The nomogram model may play an important role in predicting the survival rate for EHE patients, with good concordance and accuracy, and can be applied in clinical practice.

The correlation between miR -34a-3p, miR -31, PLEK2 and the occurrence, development and prognosis of colorectal cancer.

The current study aimed to explore the correlation between Mir-34A-3p, Mir-31, PLEK2 and the occurrence, development and prognosis of colorectal cancer. For this paper, 120 patients with colorectal cancer were selected as the study group, and their adjacent normal tissues were selected as the control group. The quantitative real-time PCR (QRT-PCR) method was used to detect miR-34a-3p and miR-31 in tissues, and the immunohistochemistry EnVision two-step method was used to detect PLEK2 positive expression. The expressions of miR -34a-3p, miR -31, and PLEK2 in colon cancer tissues and normal cancer tissues were compared, and the correlation between miR -34a-3p, miR -31, and PLEK2 and clinic-pathological characteristics of colorectal cancer patients were analyzed. The results showed that expression of miR -34a-3p, miR -31 and positive expression rate of PLEK2 in colorectal cancer tissues were higher than those in normal adjacent tissues (P<0.05). The expression of miR -34a-3p was related to tumor size, degree of tissue differentiation, lymph node metastasis and TNM stage (P < 0.05). The 3-year survival rate of miR -34a-3p with low expression was lower than miR -34a-3p with high expression, which was a protective factor affecting the poor prognosis of colorectal cancer (P < 0.05). The expression of miR -31 was related to tumor size and TNM stage. The 3-year survival rate of the group with high expression of miR -31 was lower than the group with low expression of miR -31, which was a risk factor affecting the poor prognosis of colorectal cancer (P < 0.05). PLEK2 positive expression was associated with lymph node metastasis, and the 3-year survival rate of the PLEK2 positive group was lower than the PLEK2 low expression group, which was a risk factor for poor prognosis of colorectal cancer (P < 0.05). In general, miR -34a-3p, miR -31, and PLEK2 are closely associated with the occurrence and development of colorectal cancer, and they are all influential factors affecting the prognosis of patients with colorectal cancer, which can provide a basis for the evaluation and treatment of patients, and are worthy of widespread clinical application.

Determining the relationship between cytokeratin expression and prognostic factors in human gastric cancer.

Determining the prognosis of gastric cancer is the most crucial step in the treatment process. Cytokeratins are intermediate filaments found in the intracellular structure of epithelial tissues. Recent researches have focused on determining the relationship between the expression of cytokeratins and the degree and prognosis of tumors. This study aimed to investigate the relationship between the incidence of cytokeratin-20 and cytokeratin-7 in patients with gastric carcinoma with factors influencing the prognosis. In this regard, the study was conducted cross-sectional. The expression of cytokeratin-20 and cytokeratin-7 was evaluated on 50 gastric adenocarcinoma specimens with different degrees of differentiation by the immunohistochemical method. We determined the relationship between the incidence of cytokeratin-20 and cytokeratin-7 with factors affecting the prognosis of patients, including the degree of differentiation of gastric cancer tissue, lymph node involvement, and the depth of tumor invasion. Data were statistically analyzed by Chi-square and Spearman tests. The results showed a statistically inverse relationship between the incidence of cytokeratin-20 and cytokeratin-7 with the degree of tissue differentiation and lymph node involvement in gastric cancer. Although there was a statistically significant relationship between the incidence of tissue invasion in gastric cancer and the incidence of cytokeratin-7, there was no association between the incidence of cytokeratin-20 and tissue invasion. In general, decreased cytokeratin-20 and cytokeratin-7 are associated with decreased tissue differentiation and increased lymph node involvement.

Clinical study on the second-line treatment of advanced esophageal squamous cell carcinoma with camrelizumab combined with apatinib and irinotecan: A single-arm, multicenter, phase II study.

319 Background: Esophageal squamous cell carcinoma (ESCC) is a kind of cancer with high incidence and high mortality in China, and there is no effective treatment at present. Camrelizumab as a single agent has shown a higher survival benefit in clinical studies of second-line treatment of ESCC, but the degree of tumor remission is limited. Therefore, anti-angiogenic drugs and low-dose chemotherapeutics were added to observe and evaluate the efficacy and safety of Camrelizumab combined with Apatinib and Irinotecan in the second-line treatment of advanced ESCC. Methods: This is a single-arm, multi-center, phase II study. Patients over 18 years old, male or female, with ECOG score of 0-2, who had received systemic first-line chemotherapy (including concurrent chemoradiotherapy for distant metastases within 6 months), and who were diagnosed as ESCC by histopathology or cytology were included in the study, there were no severe hematopoietic dysfunction, heart, lung, liver, kidney dysfunction and immune deficiency. Results: As of June 29, a total of 42 patients were enrolled, of which 16 patients can be evaluated for efficacy.Among the 16 patients, 5 were out of the group due to progress, intolerance and active withdrawal, while the rest were still in the process of clinical research. The baseline characteristics of 16 patients were as follows: most of the patients were male (75%) and the ECOG score was poor (ECOG 1-2, 93.75%). All the patients were ESCC, and the degree of tissue differentiation was moderate to low differentiation, moderate differentiation (50%), and the location of cancer was middle thoracic (37.5%); Most of the patients had not received radiotherapy (75.0%) or targeted drug therapy (87.5%); Most of the first-line chemotherapy regimens were paclitaxel plus platinum (85%), and 12.5% of the patients used fluorouracil plus platinum. Among the 16 patients, the best efficacy evaluation distribution was: 1 patient with CR, 8 patients with PR, 4 patients with SD, 2 patients with PD, ORR was 56.25%, DCR was 81.25%; the median PFS and OS were not reached. In terms of safety, the incidence of adverse reactions at any level is 75%, of which the most common adverse reactions are fatigue (50%), gastrointestinal reactions (25%) and hypertension (18.8%); adverse reactions above grade 3 are fever (12.5%), no new safety signals appeared. Conclusions: This is the first study to explore PD-1 inhibitors combined with anti-angiogenesis inhibitors and DNA topoisomerase I inhibitors as second-line treatments for advanced ESCC. Camrelizumab combined with Apatinib and Irinotecan as a second-line treatment has shown encouraging clinical efficacy and acceptable safety, and may be a favorable option for patients with advanced ESCC. A further phase III randomized trial is needed. Clinical trial information: ChiCTR2000028857.

Nomogram for Predicting the Prognoses of Patients With Pancreatic Head Cancer After Pancreaticoduodenectomy: A Population-Based Study on SEER Data.

ObjectiveIn this study, we retrieved the data available in the Surveillance, Epidemiology, and End Results database to identify the prognostic factors for patients with pancreatic head cancer who had undergone pancreaticoduodenectomy and developed a prediction model for clinical reference.MethodsWe screened the data between 1973 and 2015. Propensity score matching (PSM) was used to control for the confounding factors. Kaplan-Meier (log-rank test) curves were used to compare the survival rates. A nomogram was established using multifactorial Cox regression.ResultsIn total, 4099 patients were identified. Their median survival was 22 months, with 74.2%, 36.5%, and 26.2% survival after 1, 3, and 5 years, respectively. The median cancer-specific survival was 24.0 months, with 71.1%, 32.6%, and 21.9% survival after 1, 3, and 5 years, respectively. The results of the Cox proportional risk regression showed that age, insurance status, gender, histological type, degree of tissue differentiation, T and N stages, tumor size, extent of regional lymph node dissection, and postoperative radiotherapy or chemotherapy are independent factors affecting prognosis. PSM was used twice to eliminate any bias from the unbalanced covariates in the raw data. After PSM, the patients who had received postoperative radiotherapy were found to have a better survival prognosis and disease-specific survival prognosis than those who had not received radiotherapy [HR = 0.809, 95% CI (0.731–0.894), P < 0.001 and HR = 0.814, 95% CI (0.732–0.904), P < 0.001; respectively]. A similar result was observed for the patients who had received postoperative chemotherapy versus those who had not [HR = 0.703, 95% CI (0.633–0.78), P < 0.001 and HR = 0.736, 95% CI (0.658–0.822), P < 0.001, for survival and disease-specific survival prognoses, respectively]. Finally, the β coefficients of the Cox proportional risk regression were used to establish a nomogram.ConclusionAge, insurance status, gender, histological type, degree of differentiation, T and N stages, tumor size, regional lymph node dissection, and postoperative radiotherapy or chemotherapy are factors affecting the prognosis in pancreatic head cancer after pancreaticoduodenectomy. Postoperative radiotherapy and chemotherapy can improve patient survival. These still need to be further validated in the future.

The Role and Significance of Wnt5a in Regulating Epithelial-Mesenchymal Transition in Endometrioid Adenocarcinoma.

PurposeAs a non-classical ligand of Wnt, the abnormal regulation of Wnt5a contributes to the progression of malignant tumors; however, its effects differ depending on tumor type. Here, we evaluated the expression and significance of Wnt5a in endometrioid adenocarcinoma and its relationship with epithelial–mesenchymal transition (EMT)-related proteins.Patients and MethodsImmunohistochemical streptavidin-peroxidase method and reverse transcription polymerase chain reaction (RT-PCR) method were used to analyze the expression and correlation of Wnt5a, and EMT-related protein β-catenin, E-cadherin and enhancer of zeste homolog 2 (EZH2) in endometrial cancer tissues and cell samples of each group.ResultsThe expression of Wnt5a and E-cadherin decreased in the following order, normal endometrium > atypical hyperplasia endometrium > endometrioid adenocarcinoma. In contrast, the expression of β-catenin and EZH2 increased gradually. Moreover, Wnt5a expression was associated with the degree of tissue differentiation, International Federation of Gynecology and Obstetrics (FIGO) stage, and lymph node metastasis (all P<0.05). Wnt5a expression was also negatively correlated with β-catenin and EZH2 expression and positively correlated with E-cadherin expression. RT-PCR results further indicated that E-cadherin mRNA expression was upregulated in a Wnt5a-overexpressing Ishikawa cell line compared to cells transfected with an empty vector or negative control cells (P<0.01). Furthermore, the expression of EZH2 and β-catenin mRNA was downregulated in overexpressing cells compared to empty vector and negative control cells (P<0.01).ConclusionWnt5a may elicit a suppressive effect on endometrioid adenocarcinoma by inhibiting EMT. This study provides a theoretical basis for the pathological diagnosis and targeted therapy of endometrioid adenocarcinoma and extends our understanding of the Wnt5a signaling pathway.

Value of multiphase contrast-enhanced CT with three-dimensional reconstruction in detecting depth of infiltration, lymph node metastasis, and extramural vascular invasion of gastric cancer.

Multiphase contrast-enhanced computed tomography (CECT) can reveal the location, morphology, size, and enhancement pattern of gastric cancer (GC), whereas the three-dimensional reconstruction (3DR) technique can better display the relationships of the lesions with surrounding structures, the feeding vessels, and lymph node metastasis. Here, we investigated the value of multi-phase CECT with 3DR in detecting depth of infiltration, lymph node metastasis, and extramural vascular invasion (EMVI) of GC. The clinical and imaging data of 132 GC patients admitted to the Chongqing Hospital of Traditional Chinese Medicine and the Third Affiliated Hospital of Chongqing Medical University during the period from January 2012 to October 2019 were collected. All patients received plain and multiphase contrast-enhanced CT scans. The agreement between the results of preoperative CT evaluation and the surgical/pathological findings was compared. (I) CT findings of GC of 3 differentiation levels: on the multiphase CECT, the peak enhancement percentage was highest in the portal venous phase. The CT values significantly differed among the arterial, portal venous, and equilibrium phases (P<0.05); the differences in the arterial, portal venous, and equilibrium phases were statistically significant among the well-, moderately, and poorly differentiated groups (all P<0.05); finally, the difference in the equilibrium phase was statistically significant between the well- and moderately differentiated groups (P<0.05). (II) Preoperative CT and postoperative pathology had good consistency in T staging (Kappa =0.667). (III) The Kappa values between the preoperative CT-diagnosed lymph node metastasis and postoperative pathologically showing an increasing consistency with the increase of CT enhancement differences. (IV) Preoperative CT and postoperative pathology had good consistency in N staging (Kappa =0.779). (V) Preoperative CT in displaying arterial supply to the stomach. The rate of positive EMVI was 32.6% (43/132) on preoperative CT. The positive EMVI diagnosed by preoperative CT was correlated with tumor size, growth pattern, tissue differentiation degree, T stage, and N stage (all P<0.05). Multiphase CECT combined with 3DR has high diagnostic performance in detecting the depth of infiltration, lymph node metastasis, and EMVI of GC.

Correlation between HPV infection and ovarian epithelial cancer diagnosed by Dynamic Contrast-enhanced magnetic resonance imaging information technology under exponential distribution mathematical model

This research aims to analyze the correlation between human papillomavirus (HPV) infection and ovarian epithelial cancer based on exponential distribution mathematical model, so as to provide an experimental basis for the early diagnosis of ovarian epithelial cancer by magnetic resonance imaging (MRI) in the future. In this study, 124 patients with ovarian epithelial cancer tissues pathologically confirmed in our hospital from March 31, 2017 to February 20, 2019 were selected as the experimental group, and 64 patients with normal ovarian tissues were selected as the control group, and the positive rate of HPV infection was detected by the computer cell test (CCT) system. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was constructed and adopted to analyze the scanning images. The correlation between HPV infection and pathological type, clinical stage, tissue differentiation degree, and CA125 in serum was studied by exponential distribution mathematical model. The results showed that the positive rate of HPV infection in the ovarian tissues of the experimental group was significantly higher than that of the control group (P < 0.05). Highly differentiated patients accounted for 25.97%, moderately differentiated patients accounted for 43.81%, and lowly differentiated patients accounted for 30.22%. Patients with clinical stage I-II accounted for 24.72%, patients with stage III accounted for 49.11%, and patients with stage IV accounted for 26.17%. HPV infection was significantly correlated with clinical stage III and moderate tissue differentiation by MRI of patients (P < 0.05), and extremely significantly correlated with clinical stage IV and low tissue differentiation by MRI (P < 0.001). The above findings show that the information technology of dynamic contrast-enhanced magnetic resonance imaging can clearly display the lesion metastasis of ovarian epithelial cancer patients with high soft tissue resolution.

Study on the expression of microRNA-1825 in serum of pre-operative and post-operative patients with breast cancer

By measuring the relative expression level of miR-1825 in serum of pre-operative and post-operative patients with breast cancer and healthy subjects, the clincal value of miR-1825 for pre-operative and post-operative breast cancer patients was evaluated.The serum of pre-operative breast cancer patients(n=92), post-operative breast cancer patients(n=64) and healthy subjects(n=60) were collected from General Hospital of Southern Theatre Command of PLA from October 2018 to March 2021. Real-time quantitative PCR was used to detect the relative expression of miR-1825 in the serum of breast cancer patients and healthy controls. The clinicopathological data were used to analyze the correlation between the expression level of miR-1825 and serum tumor markers level. The receiver operating characteristic curve (ROC) was used to evaluate the diagnosis value of breast cancer with miR-1825, CA15-3. Mann-Whitney U test was used for comparisons between two groups,and Kruskal-Wallis H test was used for multiple group comparisons. The correlation between miR-1825 and CEA, CA15-3, CA-125 expression were analyzed using Spearman correlation test.The relative expression level of miR-1825 in serum of pre-operative patients with breast cancer 1.290(0.705, 1.793) was significantly higher than that of healthy controls 0.18(-0.876, 0.725), but decreased after surgery and chemotherapy -0.080(-0474, 0.405). The analysis of clinicopathological characteristics found that the expression level of miR-1825 was higher in patients with stage Ⅲ-Ⅳ, low degree of tissue differentiation, and tumor larger than 2 cm[stageⅠ-Ⅱ:0.975(0.458, 1.380), stageⅢ-Ⅳ: 1.955(1.663, 2.535), U=98.000, P<0.001;low degree of tissue differentiation:1.685(1.448, 2.143), high/medium degree of tissue differentiation:0.700(0.395, 0.898), U=15.500, P<0.001; tumor smaller than 2 cm:0.935(0.438, 1.370), tumor larger than 2 cm:1.915(1.580, 2.288), U=215.500, P<0.001].Spearman analysis result showed that the expression of serum miR-1825 in breast cancer patients was linearly correlated with the expression of CEA (r=0.274, P=0.008) and CA15-3 (r=0.587, P<0.001); ROC curve result showed that miR-1825 was able to distinguish preoperative breast cancer patients from healthy people and postoperative patients. When using one biomarker to discriminate pre-operation and post-operation patients,miR-1825 had the best diagnostic efficiency,with an area under the ROC curve(AUC) of 0.914(95%CI: 0.872-0.956). miR-1825 may become a potential serum marker for the diagnosis of breast cancer and monitoring of therapeutic efficacy.

Correlation between loss of Smad4 and clinical parameters of non-small cell lung cancer: an observational cohort study

BackgroundSMAD4 has been found to be inactivated to varying degrees in many types of cancer; the purpose of this study was to investigate the correlation between SMAD4 expression in non-small cell lung cancer (NSCLC) and clinical pathological parameters.MethodsThe serum concentration of SMAD4 was measured by enzyme-linked immunosorbent assay and its histological expression was quantified by immunohistochemistry.ResultsThe serum concentration of Smad4 in patients with NSCLC was lower than that in benign lung disease patients and healthy individuals (P < 0.001) and its concentration was related to the histological classification, pathological differentiation, lymphatic metastasis and clinical stage of NSCLC. The sensitivity and specificity of serum Smad4 were 91.56% and 61.56% for screening NSCLC from healthy individuals and 84.55% and 60.36% for screening NSCLC from patients with benign lung disease. Logistic regression analysis showed that the degree of cell differentiation (P < 0.001), lymph node metastasis (P < 0.001) and clinical stage of NSCLC (P = 0.007) affected the expression of Smad4, and had a strong correlation with the expression of Smad4. The expression of Smad4 in NSCLC tissues was lower than that in normal lung tissues (P = 0.009) and its expression was related to the degree of tissue differentiation, lymph node metastasis and clinical stage (P < 0.05).ConclusionsThe downregulation or deletion of Smad4 is related to the malignant biological behavior of NSCLC and serum Smad4 could be considered as a potential molecular indicator for diagnosis and evaluation of NSCLC.

MiR‑7/SP1/TP53BP1 axis may play a pivotal role in NSCLC radiosensitivity.

MicroRNA-7 (miR-7) has been identified as a tumor suppressor in non-small cell lung cancer (NSCLC) and a radiosensitivity regulator. Numerous studies have revealed that specific protein 1 (SP1) plays a critical role in the tumorigenesis of various types of cancers and regulates radiosensitivity and tumor suppressor p53-binding protein 1 (TP53BP1), which plays an essential role in DNA repair. However, it is not clear whether miR-7 has a regulatory effect on SP1 and TP53BP1 in NSCLC. In the present study it was revealed that miR-7 directly binds to the 3′UTR of SP1, thereby suppressing SP1 expression to regulate radiosensitivity. Overexpression of miR-7 and SP1 and knockdown of miR-7 and SP1 were performed using lentiviral transfection. Protein and mRNA abundance of SP1 and TP53BP1 were determined using western blotting and RT-qPCR, respectively, while miR-7 binding to SP1 was validated using a luciferase reporter assay. Biological function analysis indicated that miR-7 negatively regulated SP1 and inhibited cell proliferation, migration, and invasion when combined with radiation. It was also revealed that the expression of TP53BP1 was positively regulated by SP1 or negatively regulated by miR-7. In conclusion, SP1 was a target of miR-7, and the decreased expression of SP1 resulting from miR-7 overexpression in NSCLC was vital for improving radiosensitivity in NSCLC cells. Moreover, SP1 expression was detected in 95 paired NSCLC and adjacent normal tissues, and it was determined that SP1 was significantly upregulated in NSCLC tissues and that its upregulation was correlated with the degree of tissue differentiation. Thus, SP1 and/or miR-7 may be potential molecular targets in NSCLC radiotherapy.

Evaluation of the relationship between CD163 positive macrophages and prognostic factors in serous ovarian tumors

Introduction: Ovarian cancer is the seventh most common cancer in women and is the fifth most common cause of mortality from malignancy. Objectives: The present study was performed to evaluate the number of CD163 positive macrophages and prognostic factors in serous ovarian tumors. Materials and Methods: In the present cross-sectional study, 43 tissue samples obtained from patients with serous ovarian tumors were selected from the pathology ward of Al-Zahra hospital, Isfahan, Iran. Then, the patients’ demographic information including age, pathological results, clinical stage of the disease, degree of tissue differentiation, the number of CD163 positive macrophages, and the five-year survival rate after the surgery were recorded and evaluated. Results: Patient age, International Federation of Gynecology and Obstetrics (FIGO) stage, histological grade, lymphatic metastasis, and the five-year survival rate were positively and significantly associated with the number of CD163 positive macrophages (P &lt;0.05). In addition, the number of CD163 positive macrophages increased the odds of the five-year survival rate in these patients by 1.490 times (P = 0.026). Conclusion: According to the results of this study, the number of CD163 positive macrophages had a significant association with the progression of ovarian cancer. Moreover, the increased number of CD163 positive macrophages increased the chance of mortality in these patients.

Expressions of Sry-related High Mobility Group Box 9 and Gastrokine-1 in Gastric Cancer and Their Relationships with Prognosis

Objective To explore the expressions of Sry-related high mobility group box 9(SOX9)and gastrokine-1(GKN1) in gastric cancer tissues and their relationships with clinicopathologic features and prognosis of patients.Methods Immunohistochemistry was used to detect the expressions of SOX9 and GKN1 in 70 cases of gastric cancer tissues and corresponding paracancerous tissues including 27 cases of intestinal metaplasia and 43 cases of normal gastric mucosa. The relationships of SOX9 and GKN1 expressions with clinicopathological features and prognosis were analyzed in gastric cancer tissues.Results The high expression rates of SOX9 in gastric cancer tissues,intestinal metaplasia,and normal gastric mucosa were 92.9%(65/70),77.8%(21/27),and 55.8%(24/43),respectively(χ 2=21.722,P<0.001). Positive nuclear and cytoplasmic staining was observed. The high nuclear expression rate of SOX9 in gastric cancer tissues was 67.1%,which was significantly higher than those of intestinal metaplasia(37.0%,P=0.007)and normal gastric mucosa(23.3%,P<0.001). The high cytoplasmic expression rate of GKN1 in normal gastric mucosa was 76.7%,which was significantly higher than those of intestinal metaplasia(44.4%,P=0.006)and gastric cancer tissues(37.1%,P<0.001). Univariate analysis demonstrated that the nuclear expression of SOX9 in gastric cancer was associated with the degree of tissue differentiation(P=0.007),while the cytoplasmic expression of GKN1 was associated with both the degree of tissue differentiation(P=0.002)and whether the pathological type was a signet-ring cell carcinoma(P=0.009). Furthermore,the nuclear expression of SOX9 was negatively correlated with the expression of GKN1 in gastric cancer(χ 2=15.424,P<0.001). The 5-year survival rates of patients with high or low nuclear expression of SOX9 were 33.8% and 67.5%,respectively(P=0.016).The 5-year survival rates of patients with high or low expression of GKN1 were 60.0% and 35.6%,respectively(P=0.044). Further research indicated that 5-year survival rate of patients with high nuclear expression of SOX9 and low expression of GKN1 was 28.8%. Cox multivariate regression analysis showed that TNM stage(stage Ⅱ:HR=7.435,95%CI:1.313-42.096,P=0.023;stage Ⅲ:HR=12.214,95%CI:2.677-55.721,P=0.001)and nuclear expression level of SOX9(HR=3.297,95%CI:1.199-9.065,P=0.021)were independent risk factors for the prognosis of gastric cancer patients.Conclusions Changes in the expressions of SOX9 and GKN1 may be associated with the malignant biological behavior of gastric cancer. SOX9 may be a potential prognostic factor. The combined detection of SOX9 and GKN1 expression and the further study of their molecular mechanism may provide new clues for early diagnosis,targeted therapy,and prognostic prediction of gastric cancer.

Distribution characteristics and clinical significance of peripheral blood stem cell-like memory T cells in patients with gastric cancer

Objective To study the distribution characteristics of peripheral blood stem cell-like memory T cells (TSCM) in patients with gastric cancer and to analyze their relationship to clinicopathological characteristics and clinical application value. Methods Thirty-two patients hospitalized with gastric cancer in our hospital from July to December, 2018 were selected as the case group. Twenty-three healthy volunteers recruited during the same period served as the control group. The percentages of TSCM, naive T cells (TN) and memory T cells (TM) were detected by flow cytometry and the differences between the two groups were compared. The relationship of clinicopathological features to TN, TSCM, TSCM/TN ratio and TM was analyzed. Results The percentages of TN and TSCM in peripheral blood of the patients were significantly lower than those of the healthy control group, while the ratio of TSCM to TN was significantly increased in the case group (all P<0.05). The proportion of TN was negatively correlated with tumor TNM stage and invasion depth, and positively correlated with the degree of tissue differentiation. The ratio of TSCM to TN was positively correlated with TNM stage, invasion depth and lymph node metastasis. Conclusions TN and the ratio of TSCM to TN in peripheral blood of patients with gastric cancer are closely related to clinical and pathological characteristics such as tumor stage and invasion depth, which could be used as a new way to evaluate the immune status of patients. TSCM might have important clinical application value in adoptive cellular immunotherapy of gastric cancer, but large-scale multi-center clinical studies are needed for further evaluation. Key words: Gastric cancer; Stem cell-like memory T cell; Naive T cell; Memory T cell; Cellular immunity

Efficacy analysis of radiotherapy combined with surgery for locally advanced rectal mucinous adenocarcinoma: a retrospective study based on data of Surveillance, Epidemiology, and End results population

To explore the efficacy of radiotherapy combined with surgery for locally advanced rectal mucinous adenocarcinoma. Clinical data of patients with locally advanced rectal mucinous adenocarcinoma (T3-4 and/or N+) diagnosed by postoperative pathology from 1992 to 2013 were retrieved from the US Surveillance, Epidemiology, and End Results (SEER) database. Patients with local excision only, tumor biopsy or combined organ excision and incomplete follow-up information were excluded. All the enrolled patients were divided into three groups according to different treatments, including surgery alone (SA) group, preoperative radiotherapy combined with surgery (RT+S) group and surgery combined with postoperative radiotherapy (S+RT) group. The extracted data included basic data of patients and tumor, treatment status, and follow-up results. The χ² test was used to compare the count data. Kaplan-Meier method was used to draw the survival curve and calculate the survival rate. The survival was analyzed and compared by Log-rank test. The R language 2.8.1 was used to match the patients as 1:1 pairing through the propensity score matching (PSM). The matching variables included gender, age at diagnosis, year at diagnosis, ethnicity, degree of tissue differentiation, TNM stage, depth of invasion, making the baseline data of subgroups comparable. The Cox proportional hazard model was used for multivariate analysis of prognostic factors. A total of 2 149 patients with locally advanced rectal mucinous adenocarcinoma were enrolled in the study, including 1 255 males (58.4%) and 894 females (41.6%). There were 706 patients (32.9%) in the SA group, 772 patients (35.9%) in the RT+S group and 671 patients (31.2%) in the S+RT group. In SA, RT+S and S+RT groups, the median overall survival time was 39, 85, and 74 months respectively; the 5-year overall survival (OS) rate was 38.7%, 56.5%, and 55.2% respectively; the median cancer-specific survival (CSS) time was 86, 127, and 111 months respectively, and the 5-year CSS rate was 53.7%, 62.2% and 60.7% respectively. In comparison among the 3 groups, the 5-year OS rate and CSS rate in the SA group were significantly lower than those in the RT+S group and S+RT group (all P<0.001); the 5-year OS rate and CSS rate between RT+S group and S+RT group were not significantly different (P=0.166 and 0.392,respectively). After the baseline data of subgroups were corrected through PSM, the 5-year OS rate and CSS rate in the SA group (n=375) were significantly lower than those in the RT+S group (n=375)(OS:40.1% vs. 54.5%, P<0.001; CSS:54.3% vs. 63.3%, P=0.023). The 5-year OS rate and CSS rate in the SA group (n=403) were also lower than those in the S+RT group (n=403) (OS:37.4% vs. 54.7%,P<0.001;CSS:51.6% vs. 61.0%,P=0.031). The 5-year OS rate and CSS rate between RT+S group (n=363) and S+RT group (n=363) were not significantly different (OS:51.7% vs. 55.5%, P=0.789; CSS:57.7% vs. 60.5%, P=0.484). Cox multivariate analysis showed that radiotherapy (HR=0.845, 95%CI: 0.790 to 0.903, P=0.001) was an independent prognostic factor for OS of locally advanced rectal mucinous adenocarcinoma; radiotherapy (HR=0.907, 95% CI: 0.835 to 0.985, P=0.021) was also an independent prognostic factor affecting CSS in patients with locally advanced rectal mucinous adenocarcinoma. As compared with surgery alone, surgery combined with preoperative or postoperative radiotherapy is beneficial to the long-term survival of patients with locally advanced rectal mucinous adenocarcinoma.

Preliminary analysis of risk prediction model for recurrence and metastasis of thoracic esophageal squamous cell carcinoma after radical surgery

Objective The aim of this study is to build a risk prediction model for the recurrence and metastasis of thoracic esophageal squamous cell carcinoma after radical surgery, and to analyze the factors affecting the disease free survival (DFS). Methods Conducted analysis of 1 191 patients with thoracic esophageal squamous cell carcinoma, who received radical resection from January 2007 to December 2011. The VaR boundary value of the risk prediction model was obtained by receiver operating characteristic (ROC) curve, and the boundary value was verified. The factors that affected DFS were analyzed by univariate analysis and Cox multiple factor prognosis analysis. Results There were 472 cases had recurrence and metastasis after treatment.There was a significant difference in VaR between patients with and without failure (t=-5.307, P<0.001). The VaR boundary value was 0.30 according to ROC curve analysis. The recurrence rate of the patients in the VaR< 0.30 group was 27.5%, which was significantly lower than 48.2% in the ≥0.30 groups (χ2=51.659, P<0.001). The univariate analysis showed that the patient′s sex, the length of the lesion, the degree of tissue differentiation and the VaR value were all factors that significantly affected the recurrence and metastasis of the patients (χ2=13.460, 21.111, 17.540, 39.175, P<0.001). Multivariate analysis showed that tissue differentiation and VaR were independent factors affecting recurrence and metastasis of patients (P<0.001). Conclusions The model can be applied to predict the recurrence and metastasis risk of patients with thoracic esophageal squamous cell carcinoma after radical surgery. Key words: Esophageal neoplasms; Neoplasms, squamous cell; Esophagectomy; Neoplasm recurrence, local; Neoplasm metastasis; Risk factors