Clinical Effect of Driver Mutations of KRAS, CDKN2A/P16, TP53, and SMAD4 in Pancreatic Cancer: A Meta-Analysis.

Abstract

Objective: To evaluate the prognostic value of driver mutations in the KRAS, CDKN2A/P16, TP53, and SMAD4 genes in pancreatic cancer to aid in the design of therapeutic strategies. Search Strategy: A systematic search was conducted using PubMed, MEDLINE, Springer, and Cochrane library to identify eligible studies published between January 1990 and June 2018 that reported an association between driver mutations in these genes and survival data. Inclusion Criteria: Articles which passed the primary screen were further scrutinized for the presence of all the following items: (1) cohort studies or case-control studies, evaluating the relationship between driver mutations and cancer; (2) cancer diagnoses clearly proved; and (3) hazard ratios (HR) and 95% confidence intervals (CIs) were characterized by sufficient information. Data Extraction and Analysis: Selection of included articles, data extraction, and methodological quality assessments were, respectively, conducted by two authors. Results: The meta-analysis was composed of 17 studies on the P53, 8 on SMAD4, 7 on CDKN2A/P16, and 2 on KRAS, containing 3373 samples. Our pooled results demonstrated that the patients with overexpression of the P53 (HR = 1.249, 95% CI = 1.003-1.554, p = 0.047), SMAD4 (HR = 1.397, 95% CI = 1.015-1.922, p = 0.040), CDKN2A/P16 (HR = 0.916, 95% CI = 0.583-1.439, p = 0.704), and KRAS (HR = 1.68, 95% CI = 1.27-2.22, p < 0.001) mutations all had poorer overall survival. Conclusion: This systematic review and meta-analysis supports the use of driver mutations in the P53, SMAD4, and KRAS genes as prognostic markers for pancreatic cancer.