title: A plasma cytokine and angiogenic factor (CAF) analysis for selection of bevacizumab therapy in patients with metastatic colorectal cancer.
abstract: This study intends to identify biomarkers that could refine the selection of patients with metastatic colorectal cancer (mCRC) for bevacizumab treatment. Pretreatment 36 plasma cytokines and angiogenic factors (CAFs) were first measured by protein microarray analysis in patients who received first-line bevacizumab-containing therapies (discovery cohort, n = 64), and further evaluated by enzyme-linked immunosorbent assay in patients treated on regimens with or without bevacizumab (validation cohort, n = 186). Factor levels were correlated with clinical outcomes, predictive values were assessed using a treatment by marker interaction term in the Cox model. Patients with lower pretreatment levels of hepatocyte growth factor (HGF) or VEGF-A(121) gain much more benefit from bevacizumab treatment as measured by progression-free survival (PFS) and overall survival (OS), while angiopoietin-like 4 (ANGPTL4) levels negatively correlated with PFS and response rate following bevacizumab (all adjusted interaction P < 0.05). A baseline CAF signature combining these three markers has greater predictive ability than individual markers. Signature-negative patients showed impaired survival following bevacizumab treatment (PFS, 7.3 vs 7.0 months; hazard ratio [HR] 1.03; OS, 29.9 vs 21.1 months, HR 1.33) compared with signature-positive patients (PFS, 6.5 vs 11.9 months, HR 0.52; OS, 28.0 vs 55.3 months, HR 0.67). These promising results warrant further prospective studies.
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China.|State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China.
authors.forename: Long
authors.initials: L
authors.lastname: Bai
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China.|State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China.|State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China.
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, P. R. China.
authors.forename: Cong
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China.|State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China.|State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China.
authors.forename: De-Shen
authors.initials: DS
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China.|State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China.
authors.forename: Dong-Liang
authors.initials: DL
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China.|State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China.
authors.forename: Miao-Zhen
authors.initials: MZ
authors.lastname: Qiu
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China.|State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China.
authors.forename: Hui-Yan
authors.initials: HY
authors.lastname: Luo
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China.|State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China.|State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China.
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China.|State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China.
authors.forename: Feng-Hua
authors.initials: FH
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China.|State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China.
authors.forename: Rui-Hua
authors.initials: RH
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D043925:Angiogenesis Inducing Agents / Q000097:blood*; D000068258:Bevacizumab / Q000008:administration & dosage*; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy / Q000401:mortality; D016207:Cytokines / Q000097:blood*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000097:blood*; D012042:Registries; D015996:Survival Rate
chemical_list: D043925:Angiogenesis Inducing Agents; D016207:Cytokines; D009363:Neoplasm Proteins; D000068258:Bevacizumab