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Updated: Apr 27, 2026
Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models
Published on: December 9, 2016
RNA-seq reveals determinants for irinotecan sensitivity/resistance in colorectal cancer cell lines
Xin-Xiang Li1, Hong-Tu Zheng1, Jun-Jie Peng1
1Department of Colorectal Surgery, Fudan University Shanghai Cancer Center 200032, China ; Department of Oncology, Shanghai Medical College, Fudan University Shanghai, 200032, China.
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.
Insights
Researchers identified key genes associated with irinotecan response in colorectal cancer (CRC) by analyzing gene expression. This could help select patients for chemotherapy and avoid adverse effects.
Area of Science:
- Oncology
- Genomics
- Pharmacogenomics
Background:
- Irinotecan is a vital chemotherapy for advanced colorectal cancer (CRC).
- However, its effectiveness is limited by variable patient response and severe side effects.
- Identifying predictive biomarkers for irinotecan is crucial for personalized treatment.
Purpose of the Study:
- To identify genes associated with sensitivity or resistance to irinotecan in colorectal cancer (CRC) cells.
- To explore potential biomarkers for predicting patient response to irinotecan therapy.
Main Methods:
- Correlated irinotecan response (IC50) with gene expression profiles (RNA-seq) in 20 CRC cell lines.
- Utilized biocomputation to identify significantly correlated genes.
- Validated candidate genes using quantitative real-time PCR in two CRC cell lines.
Main Results:
- Identified several genes negatively and positively correlated with irinotecan sensitivity.
- Seven candidate genes (CDC20, CTNNAL1, FZD7, CITED2, ABR, ARHGEF7, RNMT) were validated.
- Some validated genes are implicated in promoting cancer cell proliferation, potentially conferring resistance.
Conclusions:
- The study provides potential gene biomarkers for irinotecan sensitivity in colorectal cancer (CRC).
- These findings may lead to improved patient selection for irinotecan-based chemotherapy.
- Identified genes could serve as novel therapeutic targets to overcome irinotecan resistance.
