title: Gene mutations in epidermal growth factor receptor signaling network and their association with survival in Chinese patients with metastatic colorectal cancers.
abstract: Mutations of the KRAS, BRAF, and PIK3CA genes have been reported in colorectal cancer (CRC), associated with resistance to epidermal growth factor receptor (EGFR)-targeted monoclonal antibody therapy. These reports have mainly emanated from Western countries, however, and little is known about the mutation frequencies of these genes and their prognostic value in Asian patients with CRC. In this study, we analyzed the mutation frequencies of these three genes together with EGFR, and their association with overall survival in 61 Chinese patients with metastatic CRC (mCRC). Gene mutations were examined using pyrosequencing. Kaplan-Meier survival analysis and multivariate Cox proportional hazard analysis were used to assess the prognostic significance of mutations of these four genes for patients' survival. We found that the mutations of KRAS, BRAF, PIK3CA, and EGFR were present in 12 (19.7%), 3 (4.9%), 3 (4.9%), and 0 patients, respectively. Kaplan-Meier survival analysis showed that none of these gene mutations correlated significantly with patients' overall survival. Multivariate Cox proportional hazard analysis showed only treatment regimens and age to be independent prognostic factors. Our findings indicate that EGFR signaling network genes are frequently mutated in Chinese mCRC patients, and these gene mutations do not seem to be associated with patients' overall survival.
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Wangjun
authors.initials: W
authors.lastname: Liao
authors.forename: Yulin
authors.initials: Y
authors.lastname: Liao
authors.forename: Jeff X
authors.initials: JX
authors.lastname: Zhou
authors.forename: Jianming
authors.initials: J
authors.lastname: Xie
authors.forename: Jinzhang
authors.initials: J
authors.lastname: Chen
authors.forename: Weizhen
authors.initials: W
authors.lastname: Huang
authors.forename: Rongcheng
authors.initials: R
authors.lastname: Luo
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D058534:Class I Phosphatidylinositol 3-Kinases; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D015398:Signal Transduction / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D004273:DNA, Neoplasm; D066246:ErbB Receptors; D019869:Phosphatidylinositol 3-Kinases; D011518:Proto-Oncogene Proteins; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; C117307:KRAS protein, human; C484760:PIK3CA protein, human; C512478:EGFR protein, human; C482119:BRAF protein, human