Prognostic significance of K-ras mutations in pancreatic cancer: a meta-analysis.

Lian-Yuan Tao,Ling-Fu Zhang,Chun-Hui Yuan,Bin Jiang,Zhao-Lai Ma,Dian-Rong Xiu

doi:10.1186/s12957-016-0888-3

Abstract

BackgroundK-ras gene mutations are common in patients with pancreatic cancer (PC); however, their prognostic value for PC remains inconclusive. This meta-analysis was performed to quantitatively evaluate the association between K-ras mutations and survival in patients with pancreatic cancer.MethodsWe performed a comprehensive search of electronic sources including MEDLINE (via PubMed), Web of Science, and the Cochrane Library. The search covered a publication period from inception to November 2015.ResultsSeventeen studies with a total of 2249 patients with pancreatic cancer were included in the tissue detection of this study. The meta-analysis indicated a significant association between mutant K-ras genes and overall survival (OS) (HR = 1.51, 95 % CI 1.32–1.72, P < 0.001). Moreover, further subgroup analyses by ethnicity, publication year, therapy method, cancer resectability, and gene detection method all revealed that pancreatic cancer patients with the K-ras mutation had significantly poorer OS (P < 0.05). And results from four studies with 225 patients focused on plasma K-ras mutations enhanced such association (HR = 2.23, 95 % CI 1.69–2.95, P < 0.001).ConclusionsAs a prediction of poor prognosis, the detection of K-ras mutations may be a useful prognostic factor for pancreatic cancer patients.

Highlights

K-ras gene mutations are common in patients with pancreatic cancer (PC); their prognostic value for PC remains inconclusive
Core tip To our knowledge, this is the first meta-analysis of all eligible studies on the prognostic role of the K-ras mutation in patients with pancreatic cancer
Study selection criteria Studies deal with the comparison between PC patient with and without K-ras mutation fulfilling the following criteria were considered to satisfy the inclusion criteria of present study: (1) cohort studies, nested case-control studies, or case-control studies focusing on the prognostic value of K-ras mutant type in patients with pancreatic cancer; (2) gene amplification status of K-ras was detected in surgical or plasma specimens; (3) all patient diagnoses of pancreatic cancer were confirmed through histopathologic detection; (4) sufficient data were provided to calculate hazard ratios (HR) for overall survival (OS) comparing mutant K-ras with wild-type K-ras patients; and (5) more than ten patient samples with K-ras mutation were included in the original studies because small sample size may be vulnerable to selection bias

Summary

Introduction

K-ras gene mutations are common in patients with pancreatic cancer (PC); their prognostic value for PC remains inconclusive. K-ras mutations have been demonstrated to enhance cellular proliferation and induce malignant transformation, and their continuous activation played a key role in the development and maintenance of pancreatic cancer [8]. Recent meta-analyses have suggested that K-ras mutations can be used as useful biomarkers for the early detection of pancreatic cancer [9, 10]. It has been reported positive in about 65 % patients with PC. It expressed in most pancreatic cancer patients, a sensitivity of 65 %, sometimes even lower to 36 %, limits its diagnosis

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