title: RNA-seq identifies determinants of oxaliplatin sensitivity in colorectal cancer cell lines.
abstract: Oxaliplatin-based chemotherapy, such as FOLFOX, is the first-line therapy for advanced colorectal cancer (CRC) or metastatic CRC patients. However, the partial response of patients to these regimes and the severe peripheral neuropathy toxicity induced by oxaliplatin makes it urgent to figure out biomarkers for oxaliplatin sensitivity to select suitable patients who benefit from these treatments. In present work, 21 CRC cell lines with different sensitivities to oxaliplatin were applied to RNA-seq. The basal expression profiles of these cell lines were correlated to their response to oxaliplatin. Bioinformatics analysis suggested that expression of 58 genes was correlated, negatively or positively, to oxaliplatin response across the 21 CRC cell lines. These 58 genes were mainly enriched in small molecules biochemistry, Wnt/β-catenin signaling and EMT pathways. The latter two pathways were predicted to be activated in oxaliplatin-resistant CRC cell lines. Moreover, 15 genes were validated by qPCR that their expression levels were actually closely correlated to their response to oxaliplatin, in line with the biocomputation prediction. Taken together, our work might provide potential biomarkers for oxaliplatin sensitivity in CRC cell lines and therapeutic targets for combinational therapy with oxaliplatin.
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center Shanghai 200032, China ; Department of Oncology, Shanghai Medical College, Fudan University Shanghai 200032, China.
authors.forename: Xin-Xiang
authors.initials: XX
authors.lastname: Li
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center Shanghai 200032, China ; Department of Oncology, Shanghai Medical College, Fudan University Shanghai 200032, China.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Peng
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center Shanghai 200032, China ; Department of Oncology, Shanghai Medical College, Fudan University Shanghai 200032, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center Shanghai 200032, China ; Department of Oncology, Shanghai Medical College, Fudan University Shanghai 200032, China.
authors.forename: Li-Yong
authors.initials: LY
authors.lastname: Huang
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center Shanghai 200032, China ; Department of Oncology, Shanghai Medical College, Fudan University Shanghai 200032, China.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Li
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center Shanghai 200032, China ; Department of Oncology, Shanghai Medical College, Fudan University Shanghai 200032, China.
authors.forename: De-Bing
authors.initials: DB
authors.lastname: Shi
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center Shanghai 200032, China ; Department of Oncology, Shanghai Medical College, Fudan University Shanghai 200032, China.
authors.forename: Hong-Tu
authors.initials: HT
authors.lastname: Zheng
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center Shanghai 200032, China ; Department of Oncology, Shanghai Medical College, Fudan University Shanghai 200032, China.
authors.forename: San-Jun
authors.initials: SJ
authors.lastname: Cai
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D012334:RNA, Neoplasm / Q000032:analysis*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D012334:RNA, Neoplasm; D000077150:Oxaliplatin
keywords: Colorectal cancer; RNA-seq; oxaliplatin