title: Prognostic role of tumor PIK3CA mutation in colorectal cancer: a systematic review and meta-analysis.
abstract: Somatic mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase/AKT pathway play a vital role in carcinogenesis. Approximately 15%-20% of colorectal cancers (CRCs) harbor activating mutations in PIK3CA, making it one of the most frequently mutated genes in CRC. We thus carried out a systematic review and meta-analysis investigating the prognostic significance of PIK3CA mutations in CRC.
  
  
  
  Electronic databases were searched from inception through May 2015. We extracted the study characteristics and prognostic data of each eligible study. The hazard ratio (HR) and 95% confidence interval (CI) were derived and pooled using the random-effects Mantel-Haenszel model.
  
  
  
  Twenty-eight studies enrolling 12 747 patients were eligible for inclusion. Data on overall survival (OS) and progression-free survival (PFS) were available from 19 and 10 studies, respectively. Comparing PIK3CA-mutated CRC patients with PIK3CA-wild-type CRC patients, the summary HRs for OS and PFS were 0.96 (95% CI 0.83-1.12) and 1.20 (95% CI 0.98-1.46), respectively. The trim-and-fill, Copas model and subgroup analyses stratified by the study characteristics confirmed the robustness of the results. Five studies reported the CRC prognosis for PIK3CA mutations in exons 9 and 20 separately; neither exon 9 mutation nor exon 20 mutation in PIK3CA was significantly associated with patient survival.
  
  
  
  Our findings suggest that PIK3CA mutation has the neutral prognostic effects on CRC OS and PFS. Evidence was accumulating for the establishment of CRC survival between PIK3CA mutations and patient-specific clinical or molecular profiles.
authors.affiliation: Department of Anorectal Surgery, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai herrmayor@126.com.
authors.forename: Z B
authors.initials: ZB
authors.lastname: Mei
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing.
authors.forename: C Y
authors.initials: CY
authors.lastname: Duan
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: C B
authors.initials: CB
authors.lastname: Li
authors.affiliation: Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: L
authors.initials: L
authors.lastname: Cui
authors.affiliation: Division of MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston Department of Medical Oncology, Dana-Farber Cancer Institute, Boston Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ogino
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D058534:Class I Phosphatidylinositol 3-Kinases / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D009154:Mutation; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D014408:Biomarkers, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human
keywords: PIK3CA; colorectal cancer; mutation; prognosis