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// Shuangjie Wu 1, * , Jinghui Jiang 2, * , Jun Liu 1 , Xinhai Wang 1 , Yu Gan 2 and Yifan Tang 1 1 Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China 2 State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China * These authors have contributed equally to this work Correspondence to: Yu Gan, email: ganyu@shsci.org Yifan Tang, email: tangyifan618@gmail.com Keywords: SIRT1, gastrointestinal cancer, overall survival, prognosis, meta-analysis Received: March 08, 2017 Accepted: July 12, 2017 Published: August 03, 2017 ABSTRACT Sirtuin 1 (SIRT1), a well-characterized NAD + -dependent histone deacetylase, is generally up-regulated in gastrointestinal cancers. However, the prognostic value of SIRT1 in gastrointestinal cancer remains inconclusive. Therefore, we report a meta-analysis of the association of SIRT1 expression with overall survival (OS) in gastrointestinal cancer. PubMed was systematically searched for studies evaluating the expression of SIRT1 and OS in patients with gastrointestinal cancer. Fifteen studies (six evaluating colorectal cancer, three evaluating hepatocellular carcinoma, three evaluating gastric cancer, and one each evaluating pancreatic cancer, esophageal squamous cell carcinoma, and gastroesophageal junction cancer) with 3,024 patients were finally included. The median percentage of gastrointestinal cancers with high SIRT1 expression was 52.5%. Overall analysis showed an association between high SIRT1 expression and worse OS [summary hazard ratio (sHR) 1.54, 95% confidence intervals (CI) 1.21-1.96] in gastrointestinal cancer. However, heterogeneity was observed across studies, which was mainly attributed to cancer type. Subgroup analysis revealed that SIRT1 was significantly associated with worse OS in non-colorectal gastrointestinal cancer (sHR 1.82, 95% CI 1.50-2.21), in particular in gastric cancer (sHR 3.19, 95% CI 1.97-5.16) and hepatocellular carcinoma (sHR 1.53, 95% CI 1.16-2.01), with no evidence of heterogeneity or bias. However, no association was observed in colorectal cancer (sHR 1.15, 95% CI 0.81-1.62). In conclusion, high SIRT1 expression is a potential marker for poor survival in non-colorectal gastrointestinal cancer, but not in colorectal cancer.

Long non-coding RNAs (lncRNAs), which have emerged as important regulatory RNA molecules that have been implicated in carcinogenesis and cancer progression, may also serve as novel potential biomarkers for cancer diagnosis and prognosis. Our previous analysis has identified the lncRNA GHRLOS, the ghrelin antisense strand non-coding RNA gene, as one of the hub genes in the co-expression network of differentially expressed lncRNAs/mRNAs in colorectal cancer (CRC). Here, we further evaluate the expression of GHRLOS in CRC and explore its clinical significance. The expression of GHRLOS in 366 pairs of CRC and adjacent non-cancerous tissues was detected by quantitative RT-PCR assays. The results showed that the expression level of GHRLOS was significantly lower in CRC tissues than in matched non-cancerous tissues (P < 0.001). Decreased GHRLOS expression was observed in 54.4% (199/366) of cases, and was significantly correlated with the occurrence of lymph node metastasis (P = 0.033) and distant metastasis (P = 0.005). A Kaplan-Meier analysis demonstrated that decreased GHRLOS expression contributed to poor disease-free survival (log-rank test, P < 0.001) and overall survival (log-rank test, P < 0.001). Moreover, a multivariate Cox regression analysis revealed the decreased expression of GHRLOS as an independent prognostic marker of poor outcomes [disease-free survival: hazard ratio (HR) = 2.02, 95% confidence interval (CI) = 1.42-3.88; overall survival: HR = 1.96, 95% CI = 1.34-2.86] in CRC patients. In conclusion, our data suggest that the lncRNA GHRLOS might serve as a candidate biomarker of tumor metastasis and a prognostic indicator in CRC.

Previous studies that assessed the relationship between obesity, overweight, and survival in colorectal cancer (CRC) have provided conflicting results. Therefore, we quantitatively summarized existing evidence to estimate the association between obesity/overweight and overall survival (OS) in CRC patients and explored potentially important sources of variability. Eligible studies were identified via PubMed and EMBASE searches. The summary hazard ratio (sHR) was estimated using a fixed-effects or random-effects model according to the heterogeneity between the studies. Meta-regression and subgroup analyses were performed to explore potential sources of heterogeneity. A total of 29 eligible studies, with 51,303 CRC patients, were finally included. The overall analysis showed worse OS among obese patients [sHR 1.10, 95 % confidence intervals (CI) 1.06–1.15], but not among overweight patients (sHR 0.92, 95 % CI 0.86–1.00), than in normal-weight patients. Considerable heterogeneity was observed across studies, which was primarily attributed to the timing of body mass index (BMI) assessment (meta-regression p

PIK3CA mutation appears to predict a lack of response to anti-EGFR monoclonal antibody (mAb) treatment in patients with metastatic colorectal cancer (mCRC). However, the predictive value of PIK3CA mutations for survival remains inconclusive. Here, we pooled the data from published studies to estimate the association between PIK3CA mutation and survival outcomes in mCRC patients treated with anti-EGFR mAbs.Studies investigating the association of PIK3CA mutations with clinical survival outcomes of mCRC patients treated with anti-EGFR mAbs were systematically identified. The overall hazard ratio (HR) was estimated by using fixed effect model or random effect model according to heterogeneity between trails.Eight studies that reported survival outcome in 839 mCRC patients were included. In unselected patients, we found that PIK3CA mutations were significantly associated with poorer PFS [8 studies, 839 patients; HR = 1.53; 95 % confidence interval (CI) 1.28-1.84; P0.001] and OS (5 studies; 587 patients; HR = 1.28; 95 % CI 1.05-1.56; P = 0.015). With increased predictive power in KRAS wild-type patients (3 studies; 275 patients), the overall HR for PFS was 2.44 (95 % CI 1.33-4.48; P = 0.004) and was statistically significant. We also observed a worse OS in KRAS wild-type patients with PIK3CA mutations (2 studies; 163 patients; HR = 1.37; 95 % CI 0.80-2.35; P = 0.258), although the result was not statistically significant due to small sample size.PIK3CA mutation is a promising predictive biomarker for poor survival in mCRC patients treated with anti-EGFR mAbs, particularly in KRAS wild-type patients.