Higher Tumor Node Metastasis Stage Research Articles

Oncological features and prognosis of colorectal cancer in human immunodeficiency virus-positive patients: A retrospective study.

Due to the prolonged life expectancy and increased risk of colorectal cancer (CRC) among patients with human immunodeficiency virus (HIV) infection, the prognosis and pathological features of CRC in HIV-positive patients require examination. To compare the differences in oncological features, surgical safety, and prognosis between patients with and without HIV infection who have CRC at the same tumor stage and site. In this retrospective study, we collected data from HIV-positive and -negative patients who underwent radical resection for CRC. Using random stratified sampling, 24 HIV-positive and 363 HIV-negative patients with colorectal adenocarcinoma after radical resection were selected. Using propensity score matching, we selected 72 patients, matched 1:2 (HIV-positive:negative = 24:48). Differences in basic characteristics, HIV acquisition, perioperative serological indicators, surgical safety, oncological features, and long-term prognosis were compared between the two groups. Fewer patients with HIV infection underwent chemotherapy compared to patients without. HIV-positive patients had fewer preoperative and postoperative leukocytes, fewer preoperative lymphocytes, lower carcinoembryonic antigen levels, more intraoperative blood loss, more metastatic lymph nodes, higher node stage, higher tumor node metastasis stage, shorter overall survival, and shorter progression-free survival compared to patients who were HIV-negative. Compared with CRC patients who are HIV-negative, patients with HIV infection have more metastatic lymph nodes and worse long-term survival after surgery. Standard treatment options for HIV-positive patients with CRC should be explored.

CCAT 1- A Pivotal Oncogenic Long Non-Coding RNA in Colorectal Cancer.

Colorectal cancer (CRC) is ranked as the third most common cancer and second deadliest cancer in both men and women in the world. Currently, the cure rate and 5-year survival rate of CRC patients remain relatively low. Therefore, discovering a novel molecular biomarker that can be used to improve CRC screening, diagnosis, prognosis, and treatment would be beneficial. Long non-coding RNA colon cancer-associated transcript 1 (CCAT 1) has been found overexpressed in CRC and is associated with CRC tumorigenesis and treatment outcome. CCAT 1 has a high degree of specificity and sensitivity, it is readily detected in CRC tissues and is significantly overexpressed in both premalignant and malignant CRC tissues. Besides, CCAT 1 is associated with clinical manifestation and advanced features of CRC, such as lymph node metastasis, high tumor node metastasis stage, differentiation, invasion, and distant metastasis. In addition, they can upregulate oncogenic c-MYC and negatively modulate microRNAs via different mechanisms of action. Furthermore, dysregulated CCAT 1 also enhances the chemoresistance in CRC cells while downregulation of them reverses the malignant phenotypes of cancer cells. In brief, CCAT 1 serves as a potential screening, diagnostic and prognostic biomarker in CRC, it also serves as a potential therapeutic marker to treat CRC patients.

Monitoring of postoperative neutrophil-to-lymphocyte ratio, D-dimer, and CA153 in: Diagnostic value for recurrent and metastatic breast cancer.

This stydy aims to assess the value of monitoring of postoperative neutrophil-to-lymphocyte ratio (NLR), D-dimer, and carbohydrate antigen 153 (CA153) for diagnosis of breast cancer (BC) recurrence and metastasis. A cohort of 252 BC patients who underwent surgery at the First Affiliated Hospital of Anhui Medical University between August 2008 and August 2018 were enrolled in this retrospective study. All patients were examined during outpatient follow-ups every 3 months for 5 years postoperation and every 6 months thereafter. Recurrence or metastasis was recorded for 131 patients but not for the remaining 121. Retrospective analysis of hematological parameters and clinicopathological characteristics allowed comparison between the two groups and evaluation of these parameters for the recurrent and metastatic patients. Lymph node metastasis, higher tumor node metastasis (TNM) staging, and higher histological grade correlated with BC recurrence and metastasis (p < 0.05). Statistical differences were found in absolute neutrophil count (ANC), absolute lymphocyte count (ALC), CEA, CA153, D-dimer, NLR, platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) between the recurrent and metastatic and control groups (p < 0.05). Logistic regression analysis showed that CA153, D-dimer, NLR, and TNM staging were risk factors for BC recurrence and metastasis (p < 0.05). Combined values for the NLR, D-dimer, and CA153 had good diagnostic values, giving the highest area under the curve (AUC) of 0.913. High NLR, D-dimer, and CA153 values were significantly associated with recurrence and metastasis at multiple sites, lymph node metastasis, and higher TNM staging (p < 0.05). Patients with high CA153 were more likely to have bone metastases (p < 0.05), and those with high D-dimer were prone to lung metastasis (p < 0.05). With the increasing length of the postoperative period, the possibility of liver metastases gradually decreased, while that of chest wall recurrence gradually increased (p < 0.05). Monitoring postoperative NLR, D-dimer, and CA153 is a convenient, practical method for diagnosing BC recurrence and metastasis. These metrics have good predictive value in terms of sites of recurrence and metastasis and the likelihood of multiple metastases.

Expression characteristics of the yes-associated protein in breast cancer: A meta-analysis.

Background:The yes-associated protein (YAP) gene plays an important role in many malignant tumors, but its clinical significance in breast cancer remains unclear. This study aimed to explore the significance of YAP expression in breast cancer using meta-analysis.Methods:Seven databases will be searched to collect the case–control studies published on the association between YAP expression and clinical pathogenic features in breast cancer until December 2021: PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Wan Fang Database, and the Chinese Biomedical Literature Database. To perform meta-analysis, STATA 14.0 and RevMan5 software were used with odds ratio (OR) and 95% confidence interval (95% CI) as the effect index, and publication bias and sensitivity analysis were subsequently tested.Results:Form a total of 10 articles used in this study, 8 studies consisted of nontriple negative breast cancer (non-TNBC) and the other 2 of TNBC. Meta-analysis indicated a positive expression rate of YAP in non-TNBC tissues that was lower than in normal breast tissue (OR = 0.15, 95% CI = 0.10–0.21, P < .001). In contrast, the positive rate of YAP expression in TNBC was significantly higher than that in normal breast tissue (OR = 18.23, 95% CI = 8.20–40.52, P < .001). Furthermore, the positive expression rate was higher in the patients with lymph node metastasis, higher tumor node metastasis stage and histologic grade, and larger diameter in TNBC. However, there was no statistical difference in the positive expression rate of YAP between non-TNBC patients and lymph node metastasis, tumor node metastasis stage, histologic grade, and tumor size.Conclusions:YAP may participate in the occurrence and development of non-TNBC as a tumor suppressor gene; however, it may also be a carcinogenic factor in TNBC and may be a potential therapeutic target for TNBC.

SENP1 Aberrance and Its Linkage to Clinical Features, Adjuvant Regimen, and Prognosis in Patients With Surgical Non-small Cell Lung Cancer Receiving Adjuvant Chemotherapy.

BackgroundSmall ubiquitin-like modifier-specific protease 1 (SENP1) plays vital roles in cancer progression and chemoresistance, but its prognostic value in non-small cell lung cancer (NSCLC) is vague. This study aimed to explore the correlation of SENP1 with clinical features, adjuvant chemotherapy regimen, and prognosis in patients with surgical NSCLC receiving adjuvant chemotherapy.MethodsTumor and adjacent tissues were collected from 157 patients with surgical NSCLC receiving adjuvant chemotherapy. Meanwhile, tumor tissue and paired adjacent tissue specimens were obtained to evaluate SENP1 protein expression by immunohistochemistry (IHC) assay; among which, 102 pairs were used to detect SENP1 messenger RNA (mRNA) by reverse transcription quantitative PCR.ResultsSENP1 IHC score and SENP1 mRNA expression were increased in tumor tissue than adjacent tissue (p < 0.001). Besides, elevated SENP1 IHC score was correlated with > 5 cm tumor size (p = 0.045), lymph node metastasis occurrence (p = 0.003), and advanced tumor-node-metastasis (TNM) stage (p = 0.012); meanwhile, increased SENP1 mRNA expression was associated with histopathological subtype (p = 0.011), lymph node metastasis occurrence (p = 0.008), and higher TNM stage (p = 0.015). Besides, no correlation was found in SENP1 IHC score (p = 0.424) or mRNA expression (p = 0.927) with specific adjuvant chemotherapy regimen. Additionally, both the SENP1 protein (high) (p = 0.003) and mRNA high (p = 0.028) were correlated with poor disease-free survival (DFS), while SENP1 protein high was also associated with shorter overall survival (OS) (p = 0.029). Furthermore, SENP1 protein (high vs. low) was independently associated with unsatisfying DFS [p = 0.009, hazard ratio (HR) = 1.798] and OS (p = 0.049, HR = 1.735).ConclusionSENP1 may serve as a potential biomarker to improve the management of patients with surgical NSCLC receiving adjuvant chemotherapy.

Does pretreatment elevated calcitonin level cause the poor prognosis in patients with medullary thyroid cancer?

BackgroundMedullary thyroid carcinoma (MTC) patients have poor survival, tumor/node/metastasis (TNM) stage and biochemical prognosis are the most important factors. We investigated the clinical significance of calcitonin (Ctn) to assess the biochemical prognosis of MTC.MethodsThis retrospective observational study enrolled 77 MTC patients with complete information and primary surgery at the Department of Thyroid Surgery, China-Japan Union Hospital of Jilin University between 2009 and 2020. Patient and MTC characteristics were recorded. All patients were divided into remission, stable, and progression according to biochemical prognosis. We analyzed the correlation between preoperative serum Ctn, TNM stage and biochemical prognosis.ResultsElevated preoperative serum Ctn was positively correlated with TNM stage. Patients with higher Ctn, multifocality, and bilateral tumors were associated with a higher TNM stage. Multivariate logistic regression analysis showed that preoperative serum Ctn level was an independent risk factor for TNM stage. Receiver operating characteristic (ROC) analysis found the best Ctn cut-off value for predicting TNM III was 45.88 pg/mL, which had a sensitivity of 87.2% and a specificity of 65.8%. The best Ctn cut-off value for predicting TNM IV was 167.00 pg/mL, with a sensitivity of 92.9% and a specificity of 77.6%. In univariate analysis, patients with higher preoperative serum Ctn, multifocality, bilateral tumors, and higher TNM stage were more likely to progress. The optimal cut-off value for progression was 195.5 pg/mL, which had a sensitivity of 80.0% and a specificity of 70.2%. For every 1-unit increase in preoperative serum Ctn levels, the risk of progression increased by 1.004 times (P=0.008), and patients with TNM stage III [hazard ratio (HR) =9.663; 95% confidence interval (CI): 1.411, 66.156] were nearly 9.7-fold more likely to progress than those in TNM stage I/II.ConclusionsElevated preoperative serum Ctn predicted poor clinical outcomes in MTC.

Clinicopathological and prognostic significance of NM23 expression in patients with non-small cell lung cancer: A systematic review and meta-analysis.

Background:There is a heated debate on the clinicopathological features and prognostic significance with non-metastasis 23 (NM23) expression in patients with non-small cell lung cancer (NSCLC). Thus, we conducted this meta-analysis to evaluate the clinicopathological features and prognostic significance of NM23 for NSCLC patients.Methods:Pubmed, Embase, and Web of Science were exhaustively searched to identify relevant studies published prior to March, 2020. Odds radios (ORs) and hazard radios with 95% confidence intervals (CIs) were calculated to summarize the statistics of clinicopathological and prognostic assessments. Q-test and I2-statistic were utilized to assess heterogeneity across the included studies. We also performed subgroup analyses and meta-regression analyses to identify the source of heterogeneity. Publication bias was detected by Begg and Egger tests. Sensitivity analysis was used to value the stability of our results. All the data were analyzed using statistical packages implemented in R version 4.0.5.Results:Data from a total of 3170 patients from 36 studies were extracted. The meta-analysis revealed that low expression of NM23 was correlated with higher risk of NSCLC (OR = 4.35; 95% CI: 2.76–6.85; P < .01), poorer tumor node metastasis (TNM) staging (OR = 1.39; 95% CI: 1.01–1.90; P = .04), poorer differentiation degree (OR = 1.37; 95% CI: 1.01–1.86; P = .04), positive lymph node metastasis (OR = 1.83; 95% CI: 1.22–2.74; P < .01), lung adenocarcinoma (OR = 1.45; 95% CI: 1.20–1.75; P < .01), and poorer 5-year overall survival (OS) rate (hazard radio = 2.33; 95%CI: 1.32–4.11; P < .01). The subgroup analyses and meta-regression analyses suggested that the “Publication year”, “Country”, “Sample size”, and “Cutoff value” might be the source of heterogeneity in TNM staging, differentiation degree, and lymph node metastasis. Both Begg test and Egger test verified that there were publication bias in 5-year OS rate. Sensitivity analysis supported the credibility of the results.Conclusion:The reduced NM23 expression is strongly associated with higher risk of NSCLC, higher TNM staging, poorer differentiation degree, positive lymph node metastasis, lung adenocarcinoma, and poorer 5-year OS rate in NSCLC patients, which indicated that NM23 could serve as a biomarker predicating the clinicopathological and prognostic significance of NSCLC.

Assessment of Survival Model Performance Following Inclusion of Epstein-Barr Virus DNA Status in Conventional TNM Staging Groups in Epstein-Barr Virus–Related Nasopharyngeal Carcinoma

Nonanatomic prognostic factors complement the traditional anatomic staging system and could be incorporated into the tumor-node-metastasis (TNM) framework. Several diseases have incorporated nonanatomic prognostic factors into the determination of TNM staging groups. To refine TNM staging groups for Epstein-Barr virus (EBV)-related nonmetastatic nasopharyngeal carcinoma (NPC) by incorporating EBV DNA status. This multicenter prognostic study included patients with NPC treated with radiotherapy at 2 hospitals in China from January 2008 to December 2016. Progression-free survival and overall survival according to EBV DNA status and the TNM staging system were compared. Recursive partitioning analysis (RPA) combined with supervised clustering was applied to derive prognostic groupings, and then a refined RPA staging schema was developed, validated, and compared with existing staging schemes. Statistical analyses were conducted from October 1, 2020, to June 15, 2021. Curative intensity-modulated radiotherapy with or without platinum-based chemotherapy. The primary end point was progression-free survival. The performance of the staging system was assessed using the time-dependent area under the receiver operating characteristic curves and the TNM stage system's evaluation methodology. A total of 2354 patients (1709 men [72.6%]; median [interquartile range] age, 45 [38-53] years) were split into training (1372 [58.3%]), internal validation (672 [28.5%]), and external validation (310 [13.2%]) cohorts. Pretreatment EBV DNA was detected in 1338 (56.8%) patients. EBV DNA status was an independent prognostic factor: lower survival probability by higher TNM stage was evident in EBV DNA-positive patients but not in those with EBV DNA-negative disease. After integrating EBV DNA status and TNM stage, nonmetastatic NPC cases were categorized into RPA-I (T1-3N0 or EBV DNA-negative T1-3N1 cancers), RPA-II (EBV DNA-positive T1-3N1-2 or EBV DNA-negative T1-3N2-3/T4N0-3 cancers), and RPA-III (EBV DNA-positive T4N0-3/T1-3N3 cancers) groups, each with distinctly different prognosis. This system of RPA staging outperformed the current TNM stage system and 2 reported RPA staging schemes. These results were internally and externally validated. An RPA-based staging system for EBV-related NPC cases was associated with improved outcomes. This staging system may facilitate prognostic stratification and clinical trial designs.

Integrating HECW1 expression into the clinical indicators exhibits high accuracy in assessing the prognosis of patients with clear cell renal cell carcinoma

sBackgroundAlthough many intratumoral biomarkers have been reported to predict clear cell renal cell carcinoma (ccRCC) patient prognosis, combining intratumoral and clinical indicators could predict ccRCC prognosis more accurately than any of these markers alone. This study mainly examined the prognostic value of HECT, C2 and WW domain-containing E3 ubiquitin protein ligase 1 (HECW1) expression in ccRCC patients in combination with established clinical indicators.MethodsThe expression level of HECW1 was screened out by data-independent acquisition mass spectrometry (DIA-MS) and analyzed in ccRCC patients from the The Cancer Genome Atlas (TCGA) database and our cohort. A total of 300 ccRCC patients were stochastically divided into a training cohort and a validation cohort, and real-time PCR, immunohistochemistry (IHC) and statistical analyses were employed to examine the prognostic value of HECW1 in ccRCC patients.ResultsThe expression level of HECW1 usually decreased in human ccRCC specimens relative to control specimens in TCGA (p < 0.001). DIA-MS, Real-time PCR, and IHC analyses also showed that the majority of ccRCCs harbored decreased HECW1 expression compared with that in normal adjacent tissues (p < 0.001). Additionally, HECW1 expression was reduced in ccRCC cell lines compared with the normal renal cell line HK-2 (p < 0.001). Moreover, lower HECW1 expression was found in ccRCC patients with a higher tumor node metastasis (TNM) stage, bone metastasis, or first-line targeted drug resistance (p < 0.001). Low HECW1 expression indicated higher TNM stage, SSIGN (Stage, Size, Grade, and Necrosis) score and WHO/ISUP grade and poor prognosis in ccRCC patients (p < 0.05). Even after multivariable adjustment, HECW1, TNM stage, and SSIGN score served as independent risk factors. The c-index analysis showed that integrating intratumoral HECW1 expression into TNM stage or SSIGN score resulted in a higher c-index value than these indicators alone for predicting ccRCC patient prognosis.ConclusionHECW1 is a novel prognostic biomarker and therapeutic target in ccRCC, and integrating intratumoral HECW1 expression with established clinical indicators yields higher accuracy in assessing the postoperative prognosis of ccRCC patients.

Upregulation of tissue long noncoding RNA X inactive specific transcript predicts poor postoperative survival in patients with non-small cell lung cancer.

X inactive specific transcript (XIST) is a novel long noncoding RNA (lncRNA) which has been reported to be frequently upregulated in various human cancer types and to function as an oncogene. It has been reported that the expression of lncRNA XIST was upregulated in non-small cell lung cancer (NSCLC). In the present study, we aimed to investigate the clinical significance and prognostic value of XIST in patients with NSCLC.A total of 156 pairs of NSCLC and corresponding adjacent normal lung tissue samples were obtained from NSCLC patients who had undergone surgery from July 2014 to March 2019. The Student's t test was used in different treated groups for statistical analysis. The association between XIST expression and clinicopathological features of NSCLC patients was evaluated using the chi-squared test. Survival curves were plotted using Kaplan-Meier method and compared by log-rank test.The expression of XIST was significantly higher in NSCLC samples compared to non-cancerous samples (P < .001). Statistically significant correlations were observed between high tissue XIST expression level and lymph node metastasis (P = .036) and high Tumor Node Metastasis (TNM) stage (P = .002). The log-rank test indicated that patients with increased XIST expression experienced poor overall survival (P = .006). Multivariate Cox regression analysis showed that XIST expression level (hazard ratio = 2.645, 95% confidence interval: 1.672–7.393, P = .029) was an independent factors in predicting the overall survival of NSCLC patients.The present study found that XIST expression level was significantly associated with advanced pathological stage and high TNM stage in NSCLC. Furthermore, upregulation of tissue lncRNA XIST predicts poor postoperative survival in patients with NSCLC.

Prognostic value of immunological profile based on CD8+ and FoxP3+ T lymphocytes in the peritumoral and intratumoral subsites for renal cell carcinoma.

We aimed to assess an "Immunological Profile (IP)" including CD8+ and FoxP3+ T lymphocytes for renal cell carcinoma (RCC) to evaluate its effects on tumor pathological characteristics, disease progression, and survival. Adjacent normal and intratumoral specimens from 42 patients who had undergone radical nephrectomy for RCC were analyzed for counts of CD8+ and FoxP3+ T lymphocytes by immunohistochemistry. Tissue from both sites were evaluated and scored separately according to low (0) or high (1) expression of CD8 and FoxP3. A total score (min: 0, max: 4) was assigned to each patient. Thereafter, patients were divided into two groups for clinicopathologic and survival stratification based on score (IPWeak 0-2; and IPStrong 3-4). Survival curves were constructed using the Kaplan-Meier method, and a multivariable Cox regression model was used for overall survival (OS) and progression-free survival (PFS). The mean follow-up was 54.73 ± 21.34months. Poor RCC characteristics including pT3-T4, tumor necrosis, lymphovascular invasion, lymph node involvement, and larger tumor size were significantly more common in the IPWeak patients compared to IPStrong (p < 0.05). Kaplan-Meier analysis showed that IPWeak patients had worse OS (62.5 vs. 100%; p = 0.006) and PFS (50 vs. 94.4%; p = 0.002) compared to IPStrong patients. In multivariable analysis, IPWeak (HR 8.64; 95% CI 1.09-68.05, p = 0.042) and high tumor node metastasis stage (HR 45.33; 95% CI 4.69-437.68, p < 0.001) were significant independent predictors of poor PFS. Assessment of IP including CD8+ and FoxP3+ T lymphocytes in adjacent normal and intratumoral sites in RCC may serve as a good predictive marker for PFS.

Sepiapterin reductase promotes hepatocellular carcinoma progression via FoxO3a/Bim signaling in a nonenzymatic manner

Sepiapterin reductase plays an enzymatic role in the biosynthesis of tetrahydrobiopterin, which is reported in limited studies to regulate the progression of several tumors. However, the role of sepiapterin reductase in hepatocellular carcinoma remains largely unknown. Here, we found that sepiapterin reductase was frequently highly expressed in human hepatocellular carcinoma, which was significantly associated with higher T stage, higher tumor node metastasis stage, and even shorter survival of hepatocellular carcinoma patients. Furthermore, cell and animal experiments showed that sepiapterin reductase depletion inhibited cancer cell proliferation and promoted cancer cell apoptosis. Importantly, the results suggested that sepiapterin reductase enzymatic activity was not necessary for the progression of hepatocellular carcinoma, based on the comparison between SMMC-7721 and SMMC-7721 containing sepiapterin reductase mutant. Moreover, we showed that sepiapterin reductase regulated the development of hepatocellular carcinoma via the FoxO3a/Bim-signaling pathway. Collectively, our study suggests that sepiapterin reductase controls hepatocellular carcinoma progression via FoxO3a/Bim signaling in a nonenzymatic manner, which provides a potential prognostic factor and therapeutic strategy for hepatocellular carcinoma.

Correlation of Long Noncoding RNA SEMA6A-AS1 Expression with Clinical Outcome in HBV-Related Hepatocellular Carcinoma

PurposeHepatocellular carcinoma (HCC) is the seventh most commonly diagnosed cancer and the fourth-leading cause of cancer-related death worldwide. Chronic hepatitis B virus (HBV) is the leading cause of HCC in China. Emerging evidence suggests that long noncoding (lnc)-RNAs are deregulated and are involved in the development of HCC. Our previous study found that HBV X protein can promote HCC by altering lncRNA expression profiles. The purpose of this study was to investigate the expression of the lncRNA semaphorin 6A–antisense RNA 1 (SEMA6A-AS1) and its prognostic value in HBV-related HCC. MethodsSamples of HCC tissues and adjacent nontumor tissues were collected from patients who were pathologically diagnosed with HBV-related HCC after hepatectomy. Eligible patients had not received preoperative radiotherapy, chemotherapy, or embolotherapy. Real-time quantitative reverse-transcription polymerase chain reaction was performed to evaluate the expression levels of SEMA6A-AS1 in all tissue specimens. The correlations between SEMA6A-AS1 expression and clinicopathologic characteristics were analyzed using the χ2 test and the Fisher exact test. Overall survival curves constructed by the Kaplan–Meier method and univariate analysis made by Cox proportional hazards modeling were used for determining the prognostic significance of SEMA6A-AS1. FindingsSpecimens were collected from 47 patients (45 men, 2 women; mean age, 48.4 [10.7] years). SEMA6A-AS1 expression was significantly downregulated in HBV-related HCC tissues compared with that in adjacent noncancerous hepatic tissues (P < 0.01). Low levels of SEMA6A-AS1 were correlated with high α-fetoprotein level (P = 0.002), high Edmondson-Steiner tumor grade (P = 0.047), high tumor node metastasis stage (P = 0.01), capsular invasion (P = 0.005), and poor clinical response (P = 0.002). Additionally, both Kaplan–Meier estimator and univariate Cox regression analysis revealed that low SEMA6A-AS1 expression was significantly associated with poor overall survival (P < 0.05). ImplicationsThe results show that low expression of SEMA6A-AS1 was associated with a poor prognosis in patients with HBV-related HCC. It is necessary to determine the function and mechanism of SEMA6A-AS1 in HCC in order to identify it as a prognostic biomarker and therapeutic target.

Low expression of adenomatous polyposis coli 2 correlates with aggressive features and poor prognosis in colorectal cancer

ABSTRACT Currently, there are no relevant findings on the diagnostic and prognostic roles of adenomatous polyposis coli 2 (APC2) in colorectal cancer (CRC). This study investigated the clinical value of APC2 dysregulation in the prognosis of CRC. Immunohistochemical scores obtained from tissue microarrays were used to quantify the expression of APC2 protein in 201 CRC tissues and 139 adjacent normal tissues. A chi-squared test was performed to analyze the association between APC2 expression and various clinical characteristics. Differences in 5-year survival between groups were analyzed. A receiver operating characteristic (ROC) curve was generated to investigate the potential association between APC2 and CRC diagnosis. Compared with adjacent normal tissues, APC2 was downregulated in CRC tissues (P = 0.0004). Survival analyses revealed that CRC patients with high APC2 expression (96.74%) obtained better 5-year survival rates than those with low APC2 expression (88.07%). CRC patients with low APC2 expression exhibited obvious lymphovascular invasion (P = 0.010), lymph node metastasis (P = 0.007), and high tumor node metastasis (TNM) stage (P = 0.007). Furthermore, ROC curves confirmed that APC2 was associated with lymphovascular invasion (P = 0.004), lymph node metastasis (P = 0.002), and TNM staging (P = 0.002). In summary, low APC2 expression in CRC tissues was associated with poor prognosis and may be a useful biomarker for the prognosis and clinical classification of CRC.

Clinicopathological characteristics of gastric cancer with carbohydrate antigen 19-9 expression occurring in elderly individuals: An autopsy study.

The clinicopathological significance of carbohydrate antigen 19-9 (CA19-9) in gastric cancer (GC) remains obscure. Therefore, the current study aimed to clarify the clinicopathological value of CA19-9 in GC utilizing autopsy cases. We examined the expression of CA19-9 and mucin core proteins in GC immunohistochemically, and analyzed serum CA19-9 levels and clinicopathological variables or complications. We also investigated whether fucosyltransferases 2 and 3 (FUT2/3) allelic variants influence CA19-9 expression in GC. Compared to GC cases with negative CA19-9 expression (tCA19-9-N), those with positive CA19-9 expression (tCA19-9-P) demonstrated significant differences in characteristic features such as lymph node and distant organ metastases, lymphatic and venous permeation, and higher Tumor, Node, Metastasis (TNM) stages. Moreover, compared to GC cases with low serum CA19-9 levels (sCA19-9-L), those with high serum CA19-9 levels (sCA19-9-H) were related to venous permeation, higher proportion of lymph node and distant organ metastases, and higher TNM stages. Both tCA19-9-P GC and sCA19-9-H GC cases were significantly associated with coagulation abnormalities. sCA19-9-H GC cases correlated significantly with MUC1 and MUC5AC expression. FUT2/3 genotypes were not associated with CA19-9 expression in GC. These results suggest that CA19-9 can predict the risk of lymph node and distant metastases as well as of coagulation abnormalities.

High expression of IQGAP3 indicates poor prognosis in colorectal cancer patients.

The oncogene IQ motif-containing GTPase activating protein 3 (IQGAP3) is ubiquitously overexpressed in several human cancers. This study was designed to explore the expression and role of IQGAP3 in colorectal cancer. We first assessed the IQGAP3 expression level in colorectal cancer. The correlation of IQGAP3 expression with the clinicopathological characteristics and prognosis was then assessed. At last, we investigated the function of IQGAP3 in colorectal cancer by knocking down its expression in colorectal cancer cell lines. Consistent with the conclusions drawn from The Cancer Genome Atlas database, IQGAP3 was upregulated in colorectal cancer at the tissue level and cellular level. Based on immunohistochemistry results of the tissue microarrays, we demonstrated that higher expression of IQGAP3 was associated with higher tumor node metastasis stage (P = 0.005), higher incidence of lymph node metastasis (P = 0.004), and shorter overall survival (P = 0.022). Knockdown of IQGAP3 in colorectal cancer cell lines remarkably decreased their proliferation and migration abilities. Our data provide evidence that IQGAP3 significantly promote malignant progression of colorectal cancer and could serve as a potential therapeutic target.

Prognostic value of a novel scoring system using inflammatory response biomarkers in non-small cell lung cancer: A retrospective study.

BackgroundThe neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and lymphocyte‐to‐monocyte ratio (LMR) are reported to show a strong correlation with prognosis in patients with non‐small cell lung cancer (NSCLC). We aimed to describe a novel scoring system combining these ratios, termed the inflammatory response biomarker (IRB) score, and test its prognostic value in NSCLC.MethodsThe data of 261 NSCLC patients who underwent thoracoscopic radical resection in a single center were retrospectively reviewed. The IRB score was defined as follows: a high NLR (> 2.12), a high PLR (92.9), and a low LMR (< 4.57) were each scored as 1; the opposite values were scored as 0. The individual scores were added to produce the IRB score (range: 0–3).ResultsMultivariate analyses indicated that high tumor node metastasis (TNM) stage (hazard ratio [HR] 2.721, 95% confidence interval [CI] 1.597–4.989; P < 0.001) and an IRB score ≥ 2 (HR 2.696, 95% CI 1.506–4.826; P = 0.001) were independent prognostic factors for poor overall survival. Furthermore, smoking history (HR 2.953, 95% CI 1.086–8.026; P = 0.034), high TNM stage (HR 3.108, 95% CI 1.911–5.056; P < 0.001), and IRB score ≥ 2 (HR = 2.316, 95% CI: 1.389–3.861; P = 0.001) were demonstrated to be independent prognostic factors for poor disease‐free survival.ConclusionThe novel scoring system combining NLR, PLR, and LMR was an independent prognostic factor in NSCLC patients undergoing thoracoscopic radical resection and was superior to these ratios alone for predicting prognosis.

Aberrant Cyclin E and Hepatocyte Growth Factor Expression, Microvascular Density, and Micro-Lymphatic Vessel Density in Esophageal Squamous Cell Carcinoma.

Cyclin E and hepatocyte growth factor (HGF) have been observed as a multifaceted factor in many cancers, and the assessment of microvascular density (MVD) and micro-lymphatic vessel density (MLVD) has been used to quantify tumor angiogenesis and lymphangiogenesis. The aim of this study was to explore the association between expression of cyclin E, HGF, MVD, and MLVD, and clinicopathologic parameters in esophageal squamous cell carcinoma (ESCC). The expression of cyclin E, HGF, MVD, and MLVD were detected using immunohistochemically anticyclin E, HGF, CD34, and lymphatic vessel endothelial hyaluronan receptor 1 in 168 surgically resected ESCC cases and 30 normal esophageal mucosal samples. The expression levels of cyclin E, HGF, MVD, and MLVD were higher compared to controls. High cyclin E and HGF expression was found more frequently in the tumors larger than 5 cm (P < .001), with poorer differentiation (P = .034) and higher tumor node metastasis (TNM) staging (P = .009) compared to their counterparts. Both MVD and MLVD values were found to be higher in the tumors larger than 5 cm (P < .001), with poorer differentiation (P < .001) and higher TNM staging (P < .001) compared to their counterparts. Furthermore, the expression of MVD and MLVD in both the high cyclin E and high HGF expression groups was significantly higher compared to the low cyclin E and HGF expression groups (P < .001). This study demonstrated that high cyclin E and HGF expression is closely correlated with tumor size, tumor differentiation degree, and TNM stage in patients with ESCC. These findings proposed that cyclin E and HGF could serve as novel molecular markers for preoperational evaluation of ESCC.

Propofol-based Total Intravenous Anesthesia Is Associated with Better Survival Than Desflurane Anesthesia in Colon Cancer Surgery.

WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Previous research has shown different effects of anesthetics on cancer cell growth. Here, the authors investigated the association between type of anesthetic and patient survival after elective colon cancer surgery. A retrospective cohort study included patients who received elective colon cancer surgery between January 2005 and December 2014. Patients were grouped according to anesthesia received: propofol or desflurane. After exclusion of those who received combined propofol anesthesia with inhalation anesthesia or epidural anesthesia, survival curves were constructed from the date of surgery to death. After propensity matching, univariable and multivariable Cox regression models were used to compare hazard ratios for death. Subgroup analyses were performed for tumor-node-metastasis staging and postoperative metastasis. A total of 706 patients (307 deaths, 43.5%) with desflurane anesthesia and 657 (88 deaths, 13.4%) with propofol anesthesia were eligible for analysis. After propensity matching, 579 patients remained in each group (189 deaths, 32.6%, in the desflurane group vs. 87, 15.0%, in the propofol group). In the matched analyses, the propofol-treated group had a better survival, irrespective of lower tumor-node-metastasis stage (hazard ratio, 0.22; 95% CI, 0.11 to 0.42; P < 0.001) or higher tumor-node-metastasis stage (hazard ratio, 0.42; 95% CI, 0.32 to 0.55; P < 0.001) and presence of metastases (hazard ratio, 0.67; 95% CI, 0.51 to 0.86; P = 0.002) or absence of metastases (hazard ratio, 0.08; 95% CI, 0.01 to 0.62; P = 0.016). Simple propensity score adjustment produced similar findings. Propofol anesthesia for colon cancer surgery is associated with better survival irrespective of tumor-node-metastasis stage.

The downregulated long noncoding RNA DHRS4-AS1 is protumoral and associated with the prognosis of clear cell renal cell carcinoma.

BackgroundLong noncoding RNAs (lncRNAs) have been identified as important factors in cancer biology and are deregulated in many cancers. The present study aimed to determine the expression and roles of lncRNA DHRS4-AS1 in the progression of clear cell renal cell carcinoma (ccRCC).Methods and resultsUsing high-throughput RNA-sequencing data of ccRCC tumors from the Cancer Genome Atlas project, we identified lncRNA DHRS4-AS1 as significantly associated with ccRCC patients’ overall survival. We confirmed the downregulation of DHRS4-AS1 in ccRCC by assessing its expression levels in a cohort of 52 tumor and paired non-tumor samples. In addition, we found that low DHRS4-AS1 expression was significantly associated with a high tumor node metastasis stage, lymph node metastasis, advanced pathological grade and poor prognosis. Furthermore, DHRS4-AS1 overexpression inhibited the progression of cell cycles of ccRCC in vitro. These data indicate that DHRS4-AS1 functions by preventing the proliferation and invasion, inhibiting the cell cycle progression and promoting the apoptosis of ccRCC cells.ConclusionTaken together, our findings identify the role of DHRS4-AS1 as a tumor inhibitor in ccRCC for the first time, demonstrating that DHRS4-AS1 is a potential prognostic biomarker that could potentially be applied in ccRCC therapy.