title: GATA binding protein 2 overexpression is associated with poor prognosis in KRAS mutant colorectal cancer.
abstract: Colorectal cancer (CRC) is one of the most lethal cancers worldwide. Mutations in KRAS occur with the frequency of 30-50% in CRC leading to decreased therapeutic response to anti-epidermal growth factor receptor (EGFR) agents. Recently GATA2 was proven to be essential in the survival of KRAS mutant non-small cell lung cancer (NSCLC) cells. However, the association between KRAS mutation and GATA2 expression in CRC remains largely unknown. In the present study, dideoxy sequencing and immunohistochemistry were used to determine KRAS mutation and GATA2 expression, respectively, in a cohort of 236 patients. Cox proportional hazard regression and Kaplan-Meier survival analysis were performed to study the association between KRAS mutation or GATA2 expression and clinical outcomes. Kaplan-Meier analysis revealed that KRAS mutant patients with high expression of GATA2 had significantly worse long-term clinical outcomes than those with low expression of GATA2 (P<0.001). Further analysis showed that patients with both KRAS mutation and high GATA2 expression experienced significantly more unfavorable 5-year outcomes than patients with wild- type KRAS and low GATA2 expression (P=0.001). Univariate and multivariate Cox proportional hazard regression demonstrated the GATA2 expression level was an independent risk factor for overall survival of CRC patients (HR 1.645; 95% CI 1.004-2.696; P=0.048). In conclusion, the results of this study demonstrated that high expression of GATA2 is correlated with worse survival outcomes in KRAS mutant CRC patients, suggesting that GATA2 may serve as a novel biomarker for the survival of CRC patients harboring KRAS mutation.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Xu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Jiayuan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Jiabo
authors.initials: J
authors.lastname: Di
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Beihai
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Zaozao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Aidong
authors.initials: A
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Shen
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Xiangqian
authors.initials: X
authors.lastname: Su
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D050989:GATA2 Transcription Factor / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D016016:Proportional Hazards Models; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)