Degree Of Tumor Differentiation Research Articles

Clinical Value of Serum miR-106a in the Diagnosis and Prognosis of Human Papillomavirus-Positive Cervical Cancer

Introduction: Cervical cancer (CC) is a prevailing malignant tumor in women, mainly caused by human papillomavirus (HPV) infection. This study investigated miR-106a expression in the serum of HPV-positive CC patients and estimated its value in diagnosis and prognosis. Methods: We enrolled 120 CC patients as study subjects, with another 80 healthy women as controls. Clinical baseline data and clinicopathological indexes including age, tumor size, differentiation degree, FIGO stage, lymph node metastasis, and squamous cell carcinoma antigen (SCC-Ag) were recorded. Serum miR-106a expression was measured using reverse transcription-quantitative polymerase chain reaction. Receiver operating characteristic curve was employed to estimate the efficacy of miR-106a in diagnosing CC or HPV-positive CC. Under a 5-year follow-up, patient survival was recorded, and the impact of miR-106a on overall survival rate was analyzed by the Kaplan-Meier method. The logistic regression model was used to analyze whether miR-106a was an independent prognostic factor for HPV infection in CC patients. Results: Serum miR-106a was upregulated in CC patients and the level >1.365 assisted the CC diagnosis. miR-106a expression in HPV-positive CC patients was elevated relative to HPV-negative CC patients, and serum miR-106a level >1.300 distinguishing HPV positive and HPV negative. HPV positivity was linked with tumor differentiation degree, FIGO stage, lymph node metastasis, and SCC-Ag in CC patients, but not with age and tumor size. High expression of miR-106a in HPV-positive CC patients increased the risk of poor prognosis, and miR-106a expression is an independent prognostic factor for HPV infection in CC patients. Conclusion: High expression of miR-106a assists in the diagnosis of HPV-positive CC and predicts poor prognosis.

The clinicopathological and prognostic significance of mTOR and p-mTOR expression in patients with non-small cell lung cancer: A meta-analysis.

The mammalian target of rapamycin (mTOR) has a crucial role in carcinogenesis, angiogenesis, cellular proliferation, and metastasis; however, its significance in non-small cell lung cancer (NSCLC) remains contentious. Consequently, this study aims to assess the clinicopathological and prognostic importance of mTOR/p-mTOR expression in NSCLC. Literature retrieval was undertaken by searching English databases PubMed, EMBASE, Web of Science, and Cochrane Library as well as Chinese databases CNKI, Wan Fang, and VIP for full-text publications that satisfied our eligibility criteria up to November 2021. STATA 12.0 was used to conduct statistical analysis (STATA Corporation, College Station, TX). This meta-analysis includes a total of 4683 patients from 28 primary publications. mTOR/p-mTOR expression was associated with sex (OR = 0.608, 95% CI: 0.442-0.836), lymph node metastasis (OR = 2.084, 95% CI: 1.437-3.182), and CEA (OR = 1.584, 95% CI: 1.135-2.209), but not with age, histological type, depth of tumor invasion, distant metastasis, TNM stage, differentiation degree, tumor size, or smoking. In addition, the expression of mTOR/p-mTOR is related to shorter overall survival in NSCLC patients (HR = 1.415, 95% CI: 1.051-1.905). Positive mTOR/p-mTOR expression was substantially correlated with unfavorable conditions on the sex, lymph node metastases, and CEA levels. mTOR/p-mTOR may indicate a bad prognosis for NSCLC. The current findings must be confirmed and changed by other high-quality research employing a multivariate analysis on bigger sample size.

Interleukin-34 deficiency aggravates development of colitis and colitis-associated cancer in mice

Although expression of interleukin (IL)-34 is upregulated in active ulcerative colitis (UC), the molecular function and underlying mechanism are largely unclear. To investigate the function of IL-34 in acute colitis, in a wound healing model and in colitis-associated cancer in IL-34-deficient mice. Colitis was induced by administration of dextran sodium sulfate (DSS), and carcinogenesis was induced by azoxymethane (AOM). Whether the impact of IL-34 on colitis was dependent on macrophages was validated by depletion of macrophages in a murine model. The association between IL-34 expression and epithelial proliferation was studied in patients with active UC. IL-34 deficiency aggravated murine colitis in acute colitis and in wound healing phase. The effect of IL-34 on experimental colitis was not dependent on macrophage differentiation and polarization. IL-34-deficient mice developed more tumors than wild-type mice following administration of AOM and DSS. No significant difference was shown in degree of cellular differentiation in tumors between wild-type and IL-34-deficient mice. IL-34 was dramatically increased in the active UC patients as previously reported. More importantly, expression of IL-34 was positively correlated with epithelial cell proliferation in patients with UC. IL-34 deficiency exacerbates colonic inflammation and accelerates colitis-associated carcinogenesis in mice. It might be served as a potential therapeutic target in UC.

The relationships of OSBPL3 expression with KI-67 expression and KRAS mutations in CRC: implications for diagnosis and prognosis

BackgroundOSBPL3 is overexpressed in a variety of malignancies and is closely associated with tumor growth and metastasis. However, its expression and function in colorectal cancer (CRC) are unclear. We aimed to investigate its prognostic and therapeutic value in this disease by detecting its expression in CRC and its correlation with the clinicopathological characteristics and prognosis of patients.MethodsA total of 92 CRC samples were included in this study. According to the 2020 WHO diagnostic criteria, the criteria of the American Joint Committee on Cancer (AJCC) 8th edition staging system were used. OSBPL3 and Ki-67 expression in these samples was detected by immunohistochemistry. OSBPL3 mRNA expression was detected by qRT-PCR. KRAS/NRAS mutations were detected by an amplification refractory mutation system (ARMS). Data analysis was performed using the statistical analysis software Prism 8.ResultsOSBPL3 was found to be significantly overexpressed in CRC tumor tissues and was associated with worse progression-free survival and overall survival in patients. Additionally, OSBPL3 expression was negatively correlated with the degree of tumor differentiation. KRAS mutations were detected in approximately 32.6% of patients and were significantly associated with high OSBPL3 expression. In addition, OSBPL3 and Ki-67 expression was significantly correlated.ConclusionsOSBPL3 is highly expressed in CRC samples and predicts a worse prognosis. OSBPL3 may become a new potential therapeutic target for CRC.

Comparison of ER, PR Reactivity Pattern with Histologic Grade, Tumor Size and Lymph Node Status in Breast Cancer

Background & Aims : There is positive correlation of ER and PR with degree of tumor differentiation and survival and response to hormone therapy are most favourable among women who are receptor positive. Material s and Method: The present study was carried out at our institute P.D.U. Medical college, Rajkot. A Total of 130 cases of breast carcinoma were taken into consideration which included of modified radi cal mastectomies and tru cut biopsies. Data including age, tumor size, and histological grade and lymph node status retrieved from pathology department. Result seen in 4150 years age group.128 cases of breast carcinomas wer s : Maximum number 42 of cases were e found affecting females and 02 were found affecting males. Out of 130 cases 66 cases have ER, PR receptor positive. Out of 130 cases 90 cases were stage 2 and out of them 50 were ER , PR positive,83 cases were grade 2 and of them 46 were ER,PR positive, 75 cases were lymph node stage N0 and out of them 37 were ER ,PR positive. Conclusion : There is significant decrease in mortality and tumor recurrences with hormone therapy. There is positive correlation of ER,PR status with histological grade of tumor and lymph node metastasis. As the positivity was seen to decrease with advancing histological grade. It was also observed that the positivity decrease with increasing metastasis and the lymph node involvement. But there is no statistically significant correla tion found between ER PR positivity and Histological Grade, Tumor Size & Lymph Node Status in this study. Keywords: ER, PR, Breast Cancer. 78 /pISSN:22316140, eISSN:23957859 Original Article

A novel association between Bmi-1 protein expression and the SUVmax obtained by 18F-FDG PET/CT in patients with gastric adenocarcinoma.

This study aimed to examine B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) in gastric adenocarcinoma (GAC) and its association with the maximal standard uptake value (SUVmax) of preoperative fluorine-18-fludeoosyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Clinicopathological data were retrospectively collected from 60 primary GAC patients. The Bmi-1 protein expression in GAC and adjacent noncancerous tissues was examined by immunohistochemistry and western blot analysis. Pearson's correlation analysis was conducted to assess the correlation between Bmi-1 expression and the SUVmax. The Bmi-1 protein levels were significantly greater in GAC versus noncancerous tissues, and higher Bmi-1 was significantly correlated with a lower degree of tumor differentiation, higher tumor stages, more lymph node metastasis, and depth of invasion. The SUVmax value was significantly correlated with the T stage, N stage, and clinical stage, but not with age, gender, tumor size, histological differentiation degree, or Lauren classification. Moreover, a significant positive correlation between Bmi-1 and SUVmax was observed in GAC tissues. In conclusion, our findings demonstrate a novel correlation between Bmi-1 and preoperative SUVmax in GAC patients who did not receive radiotherapy, chemotherapy, or targeted treatment before surgery, and both are positively correlated with unfavorable prognostic factors and a higher grade of malignancy.

A Transcriptomic-Based Tool to Predict Gemcitabine Sensitivity in Advanced Pancreatic Adenocarcinoma

A Transcriptomic-Based Tool to Predict Gemcitabine Sensitivity in Advanced Pancreatic Adenocarcinoma

Patient-derived xenograft models for gastrointestinal tumors: A single-center retrospective study.

Patient-derived xenograft (PDX) models have shown a great efficiency in preclinical and translational applications. Gastrointestinal (GI) tumors have a strong heterogeneity, and the engraftment rate of PDX models remarkably vary. However, the clinicopathological and molecular characteristics affecting the engraftment rate still remain elusive. A total of 312 fresh tumor tissue samples from patients with GI cancer were implanted into immunodeficient mice. The median follow-up time of patients was 37 months. Patients' characteristics were compared in terms of PDX growth and overall survival. PDX models of 3-6 generations were used for drug evaluation. In total, 171 (54.8%, 171/312) PDX models were established, including 85 PDX models of colorectal cancer, 21 PDX models of esophageal cancer, and 65 PDX models of gastric cancer. Other than tumor site, histology, differentiation degree, and serum alpha-fetoprotein (AFP) level, no significant differences were found between transplantation of xenografts and patients' characteristics. For patients who had undergone neoadjuvant therapy, the incidence of tumor formation was higher in those with progressive disease (PD) or stable disease (SD). In gastric cancer, the results showed a higher transplantation rate in deficient mismatch repair (dMMR) tumors, and Ki-67 could be an important factor affecting the engraftment rate. The gene mutation status of RAS and BRAF, two important molecular markers in colorectal cancer, showed a high degree of consistency between patients' tumors and PDXs. However, no significant effects of these two mutations on PDX engraftment rate were observed. More importantly, in this study although KRAS mutations were detected in two clinical cases, evident tumor inhibition was still observed after cetuximab treatment in both PDX models and patients. A large-scale PDX model including 171 cases was successfully established for GI tumors in our center. The relationship between clinicopathological and molecular features and engraftment rates were clarified. Furthermore, this resource provides us with profound insights into tumor heterogeneity, making these models valuable for PDX-guided treatment decisions, and offering the PDX model as a great tool for personalized treatment and translation research.

Survival benefit of primary tumor resection for gastric cancer with liver metastasis: A propensity score-matched, population-based study.

Gastric cancer with liver metastasis (GCLM) is highly aggressive and has a poor prognosis. This study aims to evaluate the survival benefit of primary tumor resection (PTR) for gastric cancer with liver metastasis. Data on patients with GCLM was extracted from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015.A 1:1 propensity score matching (PSM) analysis was performed to minimize the heterogeneity between the PTR and no-PTR groups. The Kaplan-Meier method and Cox regression analysis were used to assess the impact of primary tumor resection (PTR) on overall survival (OS) and cause-specific survival (CSS). A total of 3,001 patients with GCLM were included, with 328 patients treated with primary tumor resection (PTR), whereas the other 2,673 patients were not. Patients with PTR had a significantly higher OS and CSS rate than those without PTR in unmatched and PSM cohorts. In an unmatched cohort, the median OS was 12.0 months (95% CI, 10 months to 14 months) for those who underwent PTR and 4 months (95% CI, 4 months to 5 months) for those without PTR; the median CSS for those who underwent PTR was 12.0 months (95% CI, 10 months to14 months) and 4 months (95% CI, 4 months to 5 months) for those without PTR, respectively. After PMS, the median OS was 12.0 months (95% CI, 10 months to 17 months) for those who underwent PTR and 7 months (95% CI, 5 months to 10 months) for those without PTR, respectively; the median CSS for those who underwent PTR was 12.0 months (95% CI, 11 months to 17 months) and 7 months (95% CI, 5 months to 8 months) for those without PTR, respectively. In addition, multivariate Cox analysis in the PSM cohort showed that PTR, age, degree of tumor differentiation, and chemotherapy were independent prognostic factors for OS and CSS in GCLM. Specifically, PTR was a significant protective factor for OS (HR: 0.427; 95% CI, 0.325 to 0.561, P <0.001) and CSS (HR: 0.419; 95% CI, 0.313 to 0.561, P <0.001). Primary tumor resection improves the survival of gastric cancer patients with liver metastasis.

SOX4 Mediates ATRA-Induced Differentiation in Neuroblastoma Cells.

Neuroblastoma (NB), which is considered to be caused by the differentiation failure of neural crest cells, is the most common extracranial malignant solid tumor in children. The degree of tumor differentiation in patients with NB is closely correlated with the survival rate. To explore the potential targets that mediate NB cell differentiation, we analyzed four microarray datasets from GEO, and the overlapping down- or upregulated DEGs were displayed using Venn diagrams. SOX4 was one of the overlapping upregulated DEGs and was confirmed by RT-qPCR and Western blot in ATRA-treated NGP, SY5Y, and BE2 cells. To clarify whether SOX4 was the target gene regulating NB cell differentiation, the correlation between the expression of SOX4 and the survival of clinical patients was analyzed via the R2 database, SOX4 overexpression plasmids and siRNAs were generated to change the expression of SOX4, RT-qPCR and Western blot were performed to detect SOX4 expression, cell confluence or cell survival was detected by IncuCyte Zoom or CCK8 assay, immunocytochemistry staining was performed to detect cells' neurites, and a cell cycle analysis was implemented using Flow cytometry after PI staining. The results showed that the survival probabilities were positively correlated with SOX4 expression, in which overexpressing SOX4 inhibited NB cell proliferation, elongated the cells' neurite, and blocked the cell cycle in G1 phase, and that knockdown of the expression of SOX4 partially reversed the ATRA-induced inhibition of NB cell proliferation, the elongation of the cells' neurites, and the blocking of the cell cycle in the G1 phase. These indicate that SOX4 may be a target to induce NB cell differentiation.

Loss of GNE Predicts Lymph Node Metastasis in Early Gastric Cancer.

Endoscopic surgery is increasingly utilized for the treatment of early gastric cancer (EGC) worldwide, whereas lymph node metastasis (LNM) remains a critical risk factor for the relapse of EGC after endoscopic surgery. Therefore, identifying potential predictive factors and understanding the molecular mechanisms are urgently needed for improving the outcome of EGC patients with LNM. UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) is the key enzyme in the process of biosynthesis of CMP-Neu5Ac from UDP-N-acetylglucosamine (UDP-GlcNAc), which acts as a substrate for several reactions in glycan metabolism. In this study, we found that GNE was down-regulated in EGC patients with LNM. GNE expression as well as localization, tumor size, intravascular tumor thrombi and Lauren's classification were further identified as independent predictive factors for LNM. Combining GNE expression with traditional risk factors, including tumor size and differentiation degrees, could generate a better model for predicting LNM in EGC patients. Overall, our study implies that low GNE expression is a potential predictor of LNM in EGC.

SURVIVAL RATES FOR STAGE 3 OVARIAN CANCER. PROGNOSTIC FACTORS

Introduction. At the present stage, the therapy of patients with stage 3 ovarian cancer remains insufficiently effective. Modern methods of treatment of patients are accompanied by low survival, which requires the study of additional prognostic factors to individualize treatment.&#x0D; Methods. The study is based on the results of treatment of 136 patients with stage 3 ovarian cancer. The three- and five-year overall and recurrence-free survival of ovarian cancer patients, in correlation with treatment and prognosis, namely, histological type of tumor, degree of tumor differentiation, and tumor resuscitation after surgery, was studied and evaluated.&#x0D; Results. In the structure of ovarian cancer stage 3 for 2014-2019 in Ivano-Frankivsk region a three-year overall survival is 34%, recurrence-free survival is 17%. It was found that no patient with R1-R2 lived without recurrence for 4 years. Patients without residual tumor have a four-year recurrence-free survival (29.4%). Adenocarcinoma G1 was observed in 73 patients, G2 was detected in 29 patients, G3 – respectively in 33 patients. Thus, most patients suffered from highly differentiated tumors (54.1%), 21.5% of patients had moderately differentiated carcinoma.&#x0D; Conclusions. The work was carried out according to the plan of scientific research of the Ivano-Frankivsk National Medical University (IFNMU) and is a part of the planned scientific theme of the Department of Oncology: state registration number: 0121U109033; 2021-2026 "Individualization of the treatment of cancer of the reproductive system and gastrointestinal tract by studying prognostic factors and improving diagnostic methods." The author is a direct executor of a fragment of research work. It was found that starting from the 4th year of follow-up, the overall survival was higher by 14.1% in patients who received surgery followed by adjuvant chemotherapy compared with patients who received additional neoadjuvant PCT treatment cycles (p˂0.05). Starting from the 24th month, a significantly higher recurrence-free survival was among the patients who did not receive additional neoadjuvant chemotherapy; in the 3rd year of follow-up the recurrence-free survival was 17.9% among patients who underwent surgery with subsequent adjuvant chemotherapy, which is 10.5% more than among patients who received additional neoadjuvant courses of chemotherapy. Clinical and morphological factors related to the survival of patients with stage 3 ovarian cancer have been identified. Negative prognostic factors include R2: 64.4% of patients with R0 have a three-year overall survival, which is 41% higher than in R2, respectively (p˂0.05). In case of R0, the three-year recurrence-free survival is 52.3%, while for R1 and R2 it is 23.2% and 4.4%, respectively, without disease progression (p˂0.05). The prognostic value of G for overall and recurrence-free survival in patients with ovarian cancer was assessed. Favorable prognostic factors include G1: five-year overall survival in case of G1 is 19.7%, which is 11.8% higher than in patients with G3. There were no patients with G2 (p˂0.05). The four-year recurrence-free survival of G1 is 11.2%, which is 3.5% higher than in case of G3. There were no patients with G2 (p˂0.05).&#x0D; The relapse-free survival of patients with low-differentiated tumors is significantly higher up to the 24th month of observation compared to highly differentiated tumors, from the 36th month of observation, no difference in the survival of patients of the research groups was found.

HPV-16 Expression and Loss of Cell Differentiation in Primary Bladder Tumors.

Objective Primary bladder tumors have a high degree of malignancy. To investigate the expression of human papillomavirus type 16 (HPV-16) in primary bladder tumors and the loss of cell differentiation and to explore the significance of HPV-16 detection, it is expected to be a disease. Treatment provides a theoretical basis. Methods Fifty-seven patients with primary bladder tumors admitted to our hospital from January 2019 to January 2022 were selected as the research subjects, and they were divided into HPV-related groups according to the human papillomavirus (HPV) infection status (n = 28) and HPV unrelated group (n = 29). The general data of patients were collected, the expression of HPV-16 in bladder tissue samples was detected, and the correlation between pathological parameters and HPV-16 expression was analyzed. Results Among HPV subtypes, HPV 16 subtype accounted for the highest proportion, followed by HPV-18 and HPV-6 subtypes; there was no significant difference in tumor stage (stage 1, stage a, stage 2a) between the HPV-related group and the HPV-unrelated group (stage 1, stage a, and stage 2a). P > 0.05); there was no significant difference in postoperative pathological expression (high expression and low expression) of patients (P > 0.05); there was no statistical difference in age and gender between HPV-related and HPV-unrelated groups (P > 0.05), HPV-related group and HPV-unrelated group compared daily regular drinking and smoking status, the difference was statistically significant (P < 0.05); HPV-16 expression was not correlated with tumor differentiation degree and age of patients (P > 0.05); the area under the curve (AUC) of HPV-16 for judging primary bladder tumor expression and cellular molecular deletion was 0.891, with a sensitivity of 83.94% and a specificity of 88.57%. Conclusion HPV-16 is an upper, expressed in primary bladder tumors and will participate in the differentiation and loss of cells, which can provide effective guidance and basis for the diagnosis of primary bladder tumors, which is an important factor for judging the pathological stage and prognosis of patients and can provide a theoretical reference for the formulation of therapeutic measures.

Hsa_circ_0000231 affects the progression of tongue squamous cell carcinoma by activating Wnt/β-catenin signaling pathway

Objective: To explore the action mechanism of hsa_circ_0000231 in the occurrence and development of tongue squamous cell carcinoma (TSCC). Methods: Tissue samples of 60 TSCC patients were examined. The patients, including 32 males and 28 females, aged from 36 to 84 years old, underwent surgery in the Affiliated Hospital of Nantong University and Affiliated Tumor Hospital of Nantong University from December 2014 to December 2017. Saliva samples were obtained from healthy volunteers (5 males and 5 females, aged from 40 to 75 years old) and 10 TSCC patients. The TSCC cell lines (CAL-27, Tca-8113 and HN-4) were used. The expression levels of hsa_circ_0000231 in 60 pairs of freshly matched TSCC and para-carcinoma tissue samples, 10 pairs of saliva samples and 3 TSCC cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). hsa_circ_0000231 gene interference and lentiviral transfection were constructed, hsa_circ_0000231 in TSCC cell lines CAL-27 and Tca-8113 was knocked down, and the expressions of hsa_circ_0000231 in hsa_circ_0000231 interference group (sh-circ) and no-load lentivirus group (negative control) were tested with qRT-PCR. Cells with the highest knock-down efficiency were selected for CCK-8 test, colony formation assay, transwell invasion assay and scratch assay. The expressions of EMT-related proteins including E-cadherin, snail protein, N-cadherin and vimentin and proteins related to Wnt/β-catenin signaling pathway including β-catenin, C-myc, Bcl-2, MMP-9 and Cyclin D1 were measured by western blot. After TSCC cells in the interference group were co-cultured with Wnt/β-catenin pathway activator LiCl, the expressions of above proteins were re-measured by western blot. TSCC cells in interference group and control group were subcutaneously injected into nude mice to compare the effect of hsa_circ_0000231 knockdown on the growths of the tumors grafted subcutaneously in the nude mice. Statistical analysis software 25.0 was used for data analysis, and t-test or chi-square test was used for comparison between groups. Results: hsa_circ_0000231 was highly expressed in the tissue and saliva samples of TSCC patients and cell lines CAL-27, Tca-8113 and HN-4, but lowly expressed in paired para-carcinoma tissues, saliva samples of healthy people and normal human oral keratinocytes (all P<0.05). Log-rank univariate analysis showed that hsa_circ_0000231 expression level, tumor differentiation degree and T stage were related to the survival of TSCC patients (all P<0.05). Multivariate Cox risk regression model analysis suggested that hsa_circ_0000231 expression level (χ2=5.77,P=0.016) and T stage (χ2=5.27,P=0.029) were independent factors for the poor prognosis of TSCC patients. Western blot showed the expressions of snail protein, N-cadherin and vimentin were down-regulated, but E-cadherin was up-regulated in interference group compared with control group. In interference group, the expressions of β-catenin, C-myc, Bcl-2, MMP-9 and CyclinD1 were down-regulated, which were reversed after TSCC cells were co-cultured with LiCl. The knockdown of hsa_circ_0000231 reduced the proliferation, invasion and metastasis abilities of CAL-27 and Tca-8113 cells, which were reversed after TSCC cells were co-cultured with LiCl. The growth rate and volume of the tumors grafted subcutaneously in interference group using LiCl were greater than those in negative control group. Conclusion: hsa_circ_0000231 is an independent prognostic factor of TSCC. Highly expressed hsa_circ_0000231 can promote the proliferation, invasion and metastasis of TSCC cells.

Pro-Inflammatory and Anti-Inflammatory Salivary Cytokines in Breast Cancer: Relationship with Clinicopathological Characteristics of the Tumor.

The aim of the work was to compare the salivary cytokine profile of breast cancer patients with the clinicopathological characteristics of the tumor. The study included 113 patients with breast cancer (main group, mean age 54.1 years) and 111 patients with breast fibroadenomas (control group, mean age 56.7 years). Before treatment, saliva samples were collected from all patients and the content of cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, MCP-1, and TNF-α) was determined. The content of cytokines in saliva correlates well with the clinicopathological characteristics of breast cancer. The level of all salivary cytokines increases at advanced stages of breast cancer and at a low degree of tumor differentiation. The exception is MCP-1, for which there is an extremely high content for well-differentiated breast cancer. A statistically significant increase in the content of MCP-1, IL-1β, IL-2, IL-4, and IL-10 was found in triple-negative breast cancer. For the first time, the correlation of salivary levels of TNF-α, IL-1β, and IL-6 with HER2 status, MCP-1, IL-1β, IL-2, and IL-4 with the hormonal status of the tumor was shown. The relationship between the level of IL-2, IL-10, and IL-18 in saliva with the level of Ki-67 expression has been established.

Prognostic Role of Carcinoembryonic Antigen (CEA) in Colorectal Carcinoma

Background: Preoperative carcinoembryonic antigen (CEA) level is considered as a factor predictive of survival in colorectal cancer patients. Patients with normal (&lt;5 ng/ml) or lower pre- operative CEA levels were reported to have significantly longer survival. Objective: To evaluate the prognostic significance of preoperative CEA levels of patients with colorectal cancer in Taiwan. Methods: Between Jan 2016 and Dec 2017, 39 patients with histologically confirmed colorectal cancers were evaluated retrospectively at the General Surgery Department of Hayatabad Medical Complex Peshawar. All patients had undergone potentially curative surgery. Patients with metastatic diseases were not included. 5-Fluorouracil-based adjuvant chemotherapy was administered if the patients had Dukes’ C disease. Reference to the Dukes’ classification was according to the classical criteria described in 1932 for carcinoma of the rectum and adapted for use in colonic tumors. Data on gender, age, degree of tumor differentiation, location of the tumor, tumor size, lymph node metastasis, penetration of the bowel wall and preoperative CEA levels were analyzed to deter mine their association with survival. Blood samples for CEA measurement were taken a few days before operation and were analyzed using the radioimmunoassay method. Results: Total 39 patients were included in the study. Age ranged between 30-80 years with a mean age of 55 years. There were 26(66.7%) males and 13(33.3%) females, with male to female ratio of 2:1. Patients with preoperative CEA levels of &lt;5 ng/ml had significantly longer survival than those with preoperative CEA levels of &gt;5 ng/ml. The median 5 years survival rate for patients with preoperative CEA &lt;5 ng/ml was 51.2 months, while 35.5 years for &gt;5 ng/ml patients respectively (p &lt; 0.001). The tumour was primary located at the colon in 23(59%) while the rest was found at the rectum 16(41%). Tumour size was &lt;2cm in 25(64.1%) and &gt;2cm in 14(35.9%) patients. ...............

Expression and significance of miR-34 with PI3K, AKT and mTOR proteins in colorectal adenocarcinoma tissues

This research was carried out to investigate the expression of miR-34a, miR-34b and p-PI3K, p-AKT, and mTOR proteins in colorectal adenocarcinoma and corresponding distal cutaneous normal mucosal tissues and their relationship with the clinicopathological parameters of colorectal adenocarcinoma as well as the correlation between miR-34a, miR-34b and PI3K/AKT/mTOR signaling pathway. The expression of p-PI3K, p-AKT, and mTOR proteins in 67 colorectal adenocarcinomas and the corresponding distal cut-off normal mucosa were assayed by immunohistochemistry. Their relationship with clinicopathological parameters and the correlation of the three proteins were evaluated. The expression of miR-34a and miR-34b in colorectal adenocarcinoma and the corresponding distal cutaneous normal mucosa was detected by applying real-time quantitative PCR. The correlation between colorectal adenocarcinoma tissue miR-34a, miR-34b and p-PI3K, p-AKT, and mTOR proteins, respectively, was analyzed. Results showed that the expression of p-PI3K, p-AKT and mTOR proteins in colorectal adenocarcinoma tissues was higher than that in the corresponding distal cutaneous normal mucosa (P=0.000), and there was a positive correlation between the expression of the three proteins in colorectal adenocarcinoma tissues. The expression of p-PI3K and p-AKT protein in colorectal adenocarcinoma tissues were correlated with tumor size, differentiation degree, infiltration degree, lymph node metastasis and TNM stage (P<0.05). The expression of mTOR protein was related to tumor size and differentiation degree (P<0.05). The relative expression of miR-34a and miR-34b in colorectal adenocarcinoma tissues was less than that in the corresponding distal cutaneous normal mucosa (P<0.05), and the expression of miR-34a and miR-34b was positively correlated. The expression of miR-34a and miR-34b in colorectal adenocarcinoma tissues was negatively correlated with the expression of p-PI3K, p-AKT and mTOR proteins. In conclusion, the PI3K/AKT/mTOR signaling pathway may promote colorectal adenocarcinoma and differentially participate in differentiation, infiltration and lymph node metastasis. Also, miR-34a and miR-34b may inhibit colorectal adenocarcinoma. Importantly, miR-34a and miR-34b may affect the development and progression of colorectal adenocarcinoma by regulating PI3K/AKT/mTOR signaling pathway.

Role of MRI-Derived Radiomics Features in Determining Degree of Tumor Differentiation of Hepatocellular Carcinoma.

Background: To investigate radiomics ability in predicting hepatocellular carcinoma histological degree of differentiation by using volumetric MR imaging parameters. Methods: Volumetric venous enhancement and apparent diffusion coefficient were calculated on baseline MRI of 171 lesions. Ninety-five radiomics features were extracted, then random forest classification identified the performance of the texture features in classifying tumor degree of differentiation based on their histopathological features. The Gini index was used for split criterion, and the random forest was optimized to have a minimum of nine participants per leaf node. Predictor importance was estimated based on the minimal depth of the maximal subtree. Results: Out of 95 radiomics features, four top performers were apparent diffusion coefficient (ADC) features. The mean ADC and venous enhancement map alone had an overall error rate of 39.8%. The error decreased to 32.8% with the addition of the radiomics features in the multi-class model. The area under the receiver-operator curve (AUC) improved from 75.2% to 83.2% with the addition of the radiomics features for distinguishing well- from moderately/poorly differentiated HCCs in the multi-class model. Conclusions: The addition of radiomics-based texture analysis improved classification over that of ADC or venous enhancement values alone. Radiomics help us move closer to non-invasive histologic tumor grading of HCC.

CDX2 and Ki-67 Expression in Gastric Carcinoma and Its Association with Clinocopathological Parameters

Background: CDX2 has been established as a good prognostic marker for colorectal carcinomas. Differentiated adenocarcinomas are characterized by higher CDX2 expression than undifferentiated tumors with stronger reactivity in intestinal phenotypes. There is a close correlation between the degree of tumor differentiation and the Ki-67 score. It was also observed that strong CDX2 expression was associated with low Ki-67 index whereas negative or dim CDX2 expression was associated with high Ki-67 index. Methods: Gastric biopsies and gastrectomy specimens with gastric carcinoma were evaluated clinicopathologically and processed for immunohistochemistry (IHC) staining to assess CDX2 and Ki-67 expression. The relationship between 2 markers and each clinicopathological parameter was evaluated. Data was statistically analysed. P&lt;0.05 were taken for statistical significance. Results: The study was done on 57 gastric adenocarcinoma cases with mean age 56.12 years. No significant correlation was found between CDX2 &amp; Ki-67 with clinical, gross &amp; microscopic parameters except for tumor location and depth of invasion. Significant correlation was detected between CDX2 (p=0.04) &amp; Ki-67 (p=0.03) with tumor location. Depth of tumor invasion was significantly associated with Ki-67 (p=0.013). No significant association between CDX2 and Ki-67 was observed. Conclusion: The statistical correlation between CDX2 &amp; Ki-67 with clinicopathological parameters proves that CDX2 &amp; Ki-67 to be the independent markers with respect to tumor site and depth of invasion (in case of Ki-67). But due to lack of association of CDX2 with Ki-67 further studies need to be done with higher sample size.

Liver Metastases: Correlation between Imaging Features and Pathomolecular Environments.

A wide range of imaging manifestations of liver metastases can be encountered, as various primary cancers preferably metastasize to the liver (organ-specific metastases), with the imaging characteristics largely depending on various primary tumor-specific factors such as histopathologic category, degree of tumor differentiation, histologic behavior, and intratumor alterations. Characteristic imaging features potentially can help provide a more precise diagnosis in some clinical settings. These settings include those of (a) primary cancers of hollow organs such as gastrointestinal organs, the lungs, and the bladder, owing to the appearance of metastases that cannot be applied to the liver, which is a parenchymal organ; (b) unknown primary tumors; (c) more than one primary tumor; (d) another emergent malignancy; and (e) transformation to a different histopathologic tumor subtype. The characteristic features include the target sign on T2-weighted MR images or during the hepatobiliary phase of hypovascular metastasis, the peripheral rim washout sign on delayed phase images, peritumor hyperintensity during the hepatobiliary phase, hypervascular metastasis, a cystic appearance with marked hyperintensity on T2-weighted images, marked hyperintensity on T1-weighted images, calcification, capsular retraction, absence of the vessel-penetrating sign, distribution of liver metastases, and rare intraductal forms of metastases. In addition to various factors associated with the primary cancer, desmoplastic reactions around the tumor-which can be observed in adenocarcinomas with peripheral and peritumor enhancement, distinct arterioportal shunts with metastases from pancreatic ductal carcinoma, and pseudocirrhosis-also can affect these findings. The authors review the characteristic imaging findings of liver metastases from various primary cancers, with a focus on the mechanisms that underlie organ-specific liver metastases. Online supplemental material is available for this article. ©RSNA, 2022.