title: Gene signatures of drug resistance predict patient survival in colorectal cancer.
abstract: Different combinations of 5-fluorouracil (5-FU), oxaliplatin, irinotecan and other newly developed agents have been used to treat colorectal cancer. Despite the advent of new treatment regimens, the 5-year survival rate for metastatic colorectal cancer remains low (~10%). Knowing the drug sensitivity of a given tumor for a particular agent could significantly impact decision making and treatment planning. Biomarkers are proven to be successful in characterizing patients into different response groups. Using survival prediction analysis, we have identified three independent gene signatures, which are associated with sensitivity of colorectal cancer cells to 5-FU, oxaliplatin or irinotecan. On the basis of the three gene signatures, three score systems were developed to stratify patients from sensitive to resistance. These score systems exhibited robustness in stratify patients in two independent clinical studies. Patients with high scores in all three drugs exhibited the lowest survival.
authors.affiliation: 1] Department of Medicine, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA, USA [2] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Division of Epidemiology and Biostatistics, College of Public Health, University of Arizona, Tucson, AZ, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.affiliation: 1] Department of Medicine, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA, USA [2] Department of Pathology, Xinxiang Medical University, Xinxiang, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Tong
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005472:Fluorouracil / Q000008:administration & dosage; D045325:HCT116 Cells; D006801:Humans; D000077146:Irinotecan; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016019:Survival Analysis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin