title: K-Ras mutation detection in liquid biopsy and tumor tissue as prognostic biomarker in patients with pancreatic cancer: a systematic review with meta-analysis.
abstract: K-Ras gene mutations have been found in most pancreatic cancers; however, conflicting data on the prognostic value of K-Ras mutations in pancreatic cancer have been published. We conducted a meta-analysis to assess its prognostic significance. Literature searches of PubMed, EMBASE, Cochrane Library, Web of Science and Google Scholar were performed through December 2015 to identify publications exploring the association of K-Ras mutation with overall survival. Forty eligible studies involving 3427 patients with pancreatic cancer were included in the present meta-analysis. Our analysis showed a hazard ratio (HR) of negative association with survival of 1.61 [95 % confidence interval (CI) 1.36-1.90; p < 0.01] in K-Ras mutant pancreatic cancer patients. In subgroup analyses, K-Ras mutations detected in tumor tissues and in liquid biopsies had HRs of 1.37 (95 % CI 1.20-1.57; p < 0.01) and 3.16 (95 % CI 2.1-4.71; p < 0.01), respectively. In addition, the HR was higher when K-Ras mutations were detected in fresh frozen samples (HR = 2.01, 95 % CI 1.28-3.16, p = 0.002) than in formalin-fixed, paraffin-embedded (FFPE) samples (HR = 1.29, 95 % CI 1.12-1.49, p < 0.01). Though K-Ras alterations are more frequent among non-East Asian individuals than East Asian individuals, there were no significant differences in HRs of survival between the two ethnic subgroups. In conclusion, this meta-analysis suggests that K-Ras mutations are associated with a worse overall survival in pancreatic cancer patients, especially when mutations are detected in liquid biopsies or fresh frozen tumor tissue samples.
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Yuanting
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Rongyuan
authors.initials: R
authors.lastname: Zhuang
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Tianshu
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai, China. weimincai@fudan.edu.cn.
authors.forename: Weimin
authors.initials: W
authors.lastname: Cai
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001706:Biopsy / Q000379:methods; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D004252:DNA Mutational Analysis; D006801:Humans; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
keywords: K-Ras mutation; Liquid biopsy; Meta-analysis; Pancreatic cancer; Prognosis; Tumor tissue