Comprehensive analysis of the correlation between GSTM1 and tumor immunity in colon cancer.

Background: Glutathione S-transferase mu 1 (GSTM1) is one of the major glutathione conjugation enzymes. Its expression and activity have been suggested to correlate with the occurrence of colon cancer; however, the role of GSTM1 in tumor immunity remains unclear. Methods: Relevant data downloaded from The Cancer Genome Atlas (TCGA), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) was used to perform a multi-dimensional expression analysis of GSTM1 in colon adenocarcinoma (COAD). The correlation between GSTM1 and tumor immunity was analyzed with multiple online tools. Then protein-protein interaction (PPI) network and functional enrichment analyses of GSTM1-associated immunomodulators were performed. Further, we developed the Cox regression model based on the GSTM1-related immunomodulators. Finally, a GSTM1-based clinical nomogram and a calibration curve was established to predict the probability and accuracy of long-term survival. Result: GSTM1 was significantly downregulated in COAD versus normal tissues. Infiltration levels of B cells, CD8+ T cells, and dendritic cells were closely correlated to GSTM1 gene copy number deletion, and GSTM1 expression levels in COAD positively correlated with dendritic cell, B cell, neutrophil, and macrophage infiltration. Functional enrichment analysis indicated 36 GSTM1-related immunomodulators are involved in immune-related pathways of regulating T cell activation and lymphocytic activation. A 2-gene prognostic risk signature based on the 36 GSTM1-related immunomodulators was built using the Cox regression model, and the risk signature in combination with stage had an area under the curve (AUC) value of 0.747 by the receiver operating characteristic method. patients with higher risk scores-calculated based on 2 gene prognostic risk characteristics and further identified as an independent prognostic factor-were associated with worse survival using the Kaplan-Meier analysis. Together, the clinical nomogram and calibration curve based on GSTM1 suggested a good prediction accuracy for long-term survival probability. Conclusions: Our study provided evidence supporting the significant role of GSTM1 in COAD immunity and suggests GSTM1 as a potential novel target for COAD immunotherapy.

An updated meta-analysis of transanal drainage tube for prevention of anastomotic leak in anterior resection for rectal cancer.

BACKGROUND: Anastomotic leakage (AL) is one of the most serious complications after anterior resection for rectal cancer. Transanal drainage tube (TDT) placement is widely used to reduce AL, but its efficacy remains controversial. We performed a meta-analysis to evaluate the effectiveness of TDT for prevention of AL, using updated evidence. METHODS: Randomized controlled trials (RCTs) and cohort studies evaluating the effectiveness of TDT for prevention of AL after anterior resection for rectal cancer were identified by using a predefined search strategy. Meta-analysis was performed to estimate the pooled rates of AL, reoperation, anastomotic bleeding and mortality separately. RESULTS: One RCT and ten cohort studies which including 1170 cases with TDT and 1262 cases without TDT were considered eligible for inclusion. Meta-analysis showed that the TDT group was associated with a significant lower rates of AL (RR: 0.42, 95% CI: 0.31-0.58, P < 0.00001) and reoperation (RR: 0.29, 95% CI: 0.19-0.45, P < 0.00001). There was no significant difference in anastomotic bleeding rate and mortality between the two groups. CONCLUSIONS: TDT placement is associated with significant lower rates of AL and reoperation, hence it is likely to be an effective method of preventing and reducing AL after rectal cancer surgery.

MicroRNA-194 modulates epithelial-mesenchymal transition in human colorectal cancer metastasis.

MicroRNAs (miRNAs), as key regulators of gene expression, are closely related to tumor occurrence and progression. MiR-194 has been proved as a tumor regulatory factor in various cancers; however, the biological function and mechanism of action in colorectal cancer (CRC) have not been well explored. In the present study, we found that miR-194 expression is upregulated in CRC clinical specimens, while overexpression of miR-194 promotes cell migration and invasion in CRC cell lines. Besides, miR-194 significantly influenced the epithelial-mesenchymal transition (EMT) markers by downregulating E-cadherin expression (P<0.01) and upregulating vimentin and MMP-2 expression (P<0.001, P<0.05). Cell migration is the cell movement related to actin cytoskeleton. In this study, we found miR-194 increased cell polarization in SW480 cells. Moreover, zymography assay showed that miR-194 significantly upregulated the gelatin-degrading activity of MMP-2 (P<0.01). Collectively, our findings suggest that miR-194 functions as a tumor promoter in CRC, which may provide new insights for the study of CRC development and metastasis.

Portal hemodynamics before and after liver resection and its correlation with post-hepatectomy liver failure in patients with Child-Pugh class A: analysis of 151 consecutive cases.

BACKGROUND/AIMS: Low portal velocity (PV) was found in cirrhotic patients, which was thought to be a risk factor for post-hepatectomy liver failure (PHLF). This study attempted to find out whether a correlation existed between portal hemodynamics and PHLF. METHODOLOGY: From December 2010 to December 2012, all consecutive patients with Child-Pugh class A underwent liver resection were included. PV and PF were measured by using Doppler ultrasound preoperatively and on postoperative day 3. Portal hemodynamics change was explored. Univariable and multivariable analysis were used to identify risk factors for PHLF. RESULTS: PHLF occurred in 25 of 151 patients, and persistent PHLF in 9 patients. Mean portal velocity change (PVmeanC) was significantly different between patients with PHLF and patients without PHLF, but it failed to be identified as independent predictor for PHLF in multivariate analysis, which found alanine aminotransferase (ALT) and Ishak score significantly associated with PHLF, and only ALT significantly associated with persistent PHLF. Subgroup analysis of the 73 cirrhotic patients also showed that none of the portal hemodynamic parameters were independent risk factors for PHLF or persistent PHLF. CONCLUSIONS: None of the portal hemodynamic parameters could be used to predict PHLF or persistent PHLF.

Influence of clinically significant portal hypertension on hepatectomy for hepatocellular carcinoma: a meta-analysis.

BACKGROUND: Clinically significant portal hypertension (PHT) is considered as a contraindication for hepatectomy according to the guidelines of the European Association for Study of Liver and the American Association for Study of Liver Diseases. However, this issue remains controversial. Here we performed a meta- analysis to evaluate the impact of PHT on the results of hepatectomy for hepatocellular carcinoma (HCC). METHODS: Cohort studies evaluating the impact of clinically significant PHT, defined as oesophageal varices and/ or splenomegaly associated with thrombocytopenia, on the results of hepatectomy for HCC were identified using a predefined search strategy. Summary risk ratios (RRs) and 95% confidence intervals (95% CIs) for PHT and outcomes after hepatectomy for HCC were calculated. RESULTS: Seven cohort studies which including 574 cases with PHT and 1,354 cases without PHT were considered eligible for inclusion. The meta-analysis showed that, in all patients, pooled RRs of post-operative liver failure, post-operative ascites, peri-operative blood transfusion, operative mortality, 3- and 5-year overall survival associated with PHT were 2.23 (95% CI: 1.48-3.34, P=0.0001), 1.77 (95% CI: 1.19-2.64, P=0.005), 1.23 (95% CI: 1.03-1.49, P=0.03), 2.58 (95% CI: 1.12-5.96, P=0.03), 0.82 (95% CI: 0.75-0.88, P<0.00001) and 0.76 (95% CI: 0.69-0.85, P<0.00001), respectively. In subgroup analysis, similar results were found in Child-Pugh class A patients. CONCLUSION: This meta-analysis suggests that presence of oesophageal varices and/or splenomegaly associated with thrombocytopenia is associated with higher rates of post-operative complications and poor long-term survival after hepatectomy for HCC.

Anatomic versus non-anatomic liver resection for hepatocellular carcinoma: a systematic review.

BACKGROUND/AIMS: To evaluate the feasibility and therapeutic effects of anatomic liver resection versus non-anatomic liver resection for hepatocellular carcinoma. METHODOLOGY: Randomized controlled trials and non-randomized trials comparing the clinical effectiveness between anatomic and non-anatomic liver resection for hepatocellular carcinoma were identified by using a predefined search strategy. A meta-analysis was performed to estimate pooled survival and recurrence rate. RESULTS: No Randomized controlled trial was identified. Twelve non-randomized comparative trials (10 in English and 2 in Chinese) including total 1,829 cases, 1,005 cases in anatomic resection group and 824 cases in non-anatomic resection group, were included in this review. Meta-analysis showed that there was no significant difference between anatomic and non-anatomic liver resection in 1-year survival rate (p = 0.98), 3-year survival rate (p = 0.75), 5-year survival rate (p = 0.38) and recurrence rate (p = 0.44). The differences in post-operative morbidity (p = 0.32) and blood loss during operation (p = 0.11) were also not statistically significant. CONCLUSIONS: Anatomic liver resection for HCC does not provide significant benefit in 1-year/3-year/5-year survival rate, recurrence rate, post-operative morbidity and blood loss during operation compared with non-anatomic resection.

Resection margin in hepatectomy for hepatocellular carcinoma: a systematic review.

BACKGROUND/AIMS: To evaluate the influence of the width of resection margin on recurrence and survival for hepatocellular carcinoma. METHODOLOGY: Randomized controlled trials and non-randomized trials evaluating the influence of the width of resection margin for HCC were identified using a predefined search strategy. A meta-analysis was performed to estimate pooled recurrence and survival rate. RESULTS: One randomized controlled trial and four non-randomized trials were identified. The only randomized controlled trial reported that a margin aiming at 2cm could decrease the recurrence rate (p=0.037) and increase the 3-year survival (p=0.02) and 5-year survival rate (p<0.01) compared with a margin aiming at 1cm. Meta-analysis showed that there was no significant difference between the group with resection margin <1cm and the group with resection margin ≥1cm in recurrence rate (p=0.08), 1-year survival (p=0.75), 3-year survival (p=0.53) and 5-year survival rate (p=0.15). CONCLUSIONS: A resection margin ≥1cm does not provide significant prognostic benefit compared with a resection margin <1cm. There is limited evidence to show that patients with a resection margin aiming at 2cm have better survival outcome than patients with a resection margin aiming at 1cm.