Meta-analysis In Colorectal Cancer Diagnosis And Therapy Advances

Colorectal cancer (CRC) is one of the most common type of cancers and a leading cause of death worldwide. Early detection, predicting survival and better treatment strategy is important to reduce the mortality of CRC.Search for new biomarkers is an important measure for CRC early detection and prognosis, and miRNAs are thought to be important potential biomarkers. Among them, microRNA21(miR21) is one of the most popular miRNAs, and it plays an important role in cancer oncogenesis and tumor progression. To date, several studies have evaluated the value of miR21in CRC diagnosis and prognosis, while the results were inconsistent. For CRC treatment, aspirin as an adjuvant therapy has gain lots of attention. Studies suggested that aspirin can not only reduce colorectal adenoma risk, but also improve CRC survival.The aim of this study is to systematically evaluate the diagnostic and prognostic value of miR21, and the value of aspirin as adjuvant therapy in CRC. Part one. Diagnostic and prognostic value of microRNA-21in colorectal cancer:a meta-analysis.Objective:The aim of this study is to systematically summarize the diagnostic and prognostic value of circulating/tissue miR21in patients with colorectal cancer.Methods:Pubmed and Embase were searched to identify eligible studies. To explore the diagnostic performance of circulating miR21, meta-analysis methods were used to pool sensitivity, specificity, positive and negative likelihood ratio, diagnostic OR and to construct a summary ROC curve. For prognostic meta-analysis, study-specific HRs of tissue miR21for survival were summarized. Subgroup and sensitivity analyses were applied to explore heterogeneity.Results:Finally,13studies were included in the meta-analyses. The pooled sensitivity, specificity, and AUC of circulating miR21were0.80[95%confidence interval (CI),0.63-0.91],0.81(95%CI0.76-0.85), and0.82(95%CI0.78-0.85) in diagnosing colorectal cancer. Patients with higher expression of tissue miR21had significant inferior overall survival (OS; pooled HR=1.54,95%CI1.13-2.11) and disease-free survival (DFS; pooled HR=1.35,95%CI1.08-1.69).Conclusions:Circulating miR21level has potential value for colorectal cancer early detection, whereas high tissue miR21level is associated with adverse colorectal cancer prognosis. MiR21is a promising biomarker for early detection and prognosis of colorectal cancer. Part two. Aspirin use after diagnosis but not pre-diagnosis improves established colorectal cancer survival:a meta-analysisObjective:The aim of this meta-analysis was to systematically assess the survival benefit of aspirin use before or after diagnosis for patients with colorectal cancer (CRC).Methods:Relevant studies were identified through searching Pubmed, Embase and Cochrane databases before May2014. Two investigators extracted data independently for baseline characteristics and outcomes from the included studies. Either a fixed-effects or a random-effects model was derived to composite the pooled HR for overall mortality and CRC-specific mortality of CRC. Subgroup and sensitivity analyses were applied to explore heterogeneity.Results:Seven studies on post-diagnosis aspirin therapy and seven studies on pre-diagnosis aspirin use were finally included in this meta-analysis. The overall survival benefit associated with post-diagnosis aspirin use represented an HR of0.84(95%CI0.75-0.94). This effect was observed both in colon cancer (HR=0.78,95%CI0.64-0.96) and in rectal cancer (HR=0.90,95%CI0.83-0.98). Besides, the survival benefit of post-diagnosis aspirin use appeared to be confined to those patients with positive prostaglandin endoperoxide synthase2(PTGS2, also known as cyclooxygenase-2, COX-2) expression (HR=0.65,95%CI0.50-0.85) and with mutated PIK3CA tumors (HR=0.58,95%CI0.37-0.90). Aspirin use post-diagnosis was not associated with CRC-specific mortality (HR=0.77,95%CI0.52-1.14). We observed no evidence of an association between pre-diagnosis aspirin use and CRC overall mortality (HR=1.01,95%CI0.96-1.06) or CRC-specific mortality (HR=0.93,95%CI0.82-1.05). Conclusions:These findings provide further indication that post-diagnosis aspirin therapy improved CRC overall survival, especially for patients with positive PTGS2(COX-2) expression and mutated PIK3CA tumors.