Abstract

The present study was conducted to evaluate the prevalence of the signaling pathways mutation rate in the Gastrointestinal (GI) tract cancers in a systematic review and meta-analysis study. The study was performed based on the PRISMA criteria. Random models by confidence interval (CI: 95%) were used to calculate the pooled estimate of prevalence via Metaprop command. The pooled prevalence indices of signal transduction pathway mutations in gastric cancer, liver cancer, colorectal cancer, and pancreatic cancer were 5% (95% CI: 3–8%), 12% (95% CI: 8–18%), 17% (95% CI: 14–20%), and 20% (95% CI: 5–41%), respectively. Also, the mutation rates for Wnt pathway and MAPK pathway were calculated to be 23% (95% CI, 14–33%) and 20% (95% CI, 17–24%), respectively. Moreover, the most popular genes were APC (in Wnt pathway), KRAS (in MAPK pathway) and PIK3CA (in PI3K pathway) in the colorectal cancer, pancreatic cancer, and gastric cancer while they were beta-catenin and CTNNB1 in liver cancer. The most altered pathway was Wnt pathway followed by the MAPK pathway. In addition, pancreatic cancer was found to be higher under the pressure of mutation compared with others based on pooled prevalence analysis. Finally, APC mutations in colorectal cancer, KRAS in gastric cancer, and pancreatic cancer were mostly associated gene alterations.

Highlights

  • The present study was conducted to evaluate the prevalence of the signaling pathways mutation rate in the Gastrointestinal (GI) tract cancers in a systematic review and meta-analysis study

  • The signaling pathway mutations were comprehensively studied by The Cancer Genome Atlas (TCGA)[1]

  • This study could be a lead for further investigations in the field of the signaling pathway mutations prevalence and might be useful for further TCGA comprehensive updates

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Summary

Introduction

The present study was conducted to evaluate the prevalence of the signaling pathways mutation rate in the Gastrointestinal (GI) tract cancers in a systematic review and meta-analysis study. The pooled prevalence indices of signal transduction pathway mutations in gastric cancer, liver cancer, colorectal cancer, and pancreatic cancer were 5% (95% CI: 3–8%), 12% (95% CI: 8–18%), 17% (95% CI: 14–20%), and 20% (95% CI: 5–41%), respectively. The most popular genes were APC (in Wnt pathway), KRAS (in MAPK pathway) and PIK3CA (in PI3K pathway) in the colorectal cancer, pancreatic cancer, and gastric cancer while they were beta-catenin and CTNNB1 in liver cancer. Liver carcinogenesis process is related to the interactions of three major pathways: the p53/p21, the p16/cyclin D1/pRB, and the Wnt/wingless[17,18] Numerous factors such as TNFα (tumour necrosis factor alpha), TGFβ (transforming growth factor beta), c-myc, IGF2R (insulin like growth factor 2 receptor), SMAD2, SMAD4, DLC-1, and HIC1 (HIC ZBTB transcriptional repressor 1) could initiate liver t­umorogenesis[17,18]

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