title: RNA-seq reveals determinants for irinotecan sensitivity/resistance in colorectal cancer cell lines.
abstract: Irinotecan is a topoisomerase I inhibitor approved worldwide as a first- and second-line chemotherapy for advanced or recurrent colorectal cancer (CRC). Although irinotecan showed significant survival advantage for patients, a relatively low response rate and severe adverse effects demonstrated the urgent need for biomarkers searching to select the suitable patients who can benefit from irinotecan-based therapy and avoid the adverse effects. In present work, the irinotecan response (IC50 doses) of 20 CRC cell lines were correlated with the basal expression profiles investigated by RNA-seq to figure out genes responsible for irinotecan sensitivity/resistance. Genes negatively or positively correlated to irinotecan sensitivity were given after biocomputation, and 7 (CDC20, CTNNAL1, FZD7, CITED2, ABR, ARHGEF7, and RNMT) of them were validated in two CRC cell lines by quantitative real-time PCR, several of these 7 genes has been proposed to promote cancer cells proliferation and hence may confer CRC cells resistance to irinotecan. Our work might provide potential biomarkers and therapeutic targets for irinotecan sensitivity in CRC cells.
authors: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center 200032, China ; Department of Oncology, Shanghai Medical College, Fudan University Shanghai, 200032, China.
authors: Xin-Xiang
authors: XX
authors: Li
authors: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center 200032, China ; Department of Oncology, Shanghai Medical College, Fudan University Shanghai, 200032, China.
authors: Hong-Tu
authors: HT
authors: Zheng
authors: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center 200032, China ; Department of Oncology, Shanghai Medical College, Fudan University Shanghai, 200032, China.
authors: Jun-Jie
authors: JJ
authors: Peng
authors: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center 200032, China ; Department of Oncology, Shanghai Medical College, Fudan University Shanghai, 200032, China.
authors: Li-Yong
authors: LY
authors: Huang
authors: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center 200032, China ; Department of Oncology, Shanghai Medical College, Fudan University Shanghai, 200032, China.
authors: De-Bing
authors: DB
authors: Shi
authors: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center 200032, China ; Department of Oncology, Shanghai Medical College, Fudan University Shanghai, 200032, China.
authors: Lei
authors: L
authors: Liang
authors: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center 200032, China ; Department of Oncology, Shanghai Medical College, Fudan University Shanghai, 200032, China.
authors: San-Jun
authors: SJ
authors: Cai
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D018938:Caco-2 Cells; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D019295:Computational Biology; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods*; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D000077146:Irinotecan; D057285:Precision Medicine; D012334:RNA, Neoplasm / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D017423:Sequence Analysis, RNA; D059004:Topoisomerase I Inhibitors / Q000494:pharmacology*
chemical_list: D014408:Biomarkers, Tumor; D012334:RNA, Neoplasm; D059004:Topoisomerase I Inhibitors; D000077146:Irinotecan; D002166:Camptothecin
keywords: CITED2; CTNNAL1; Colorectal cancer; FZD7; RNA-seq; irinotecan