Validation of Gene Expression-Based Predictive Biomarkers for Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

Cancers

卷:13

Hirokazu Okayama¹  Shotaro Fujita¹  Yasuyuki Kanke¹  Shinji Ohki¹  Koji Kono¹  Satoshi Fukai¹  Motonobu Saito¹  Wataru Sakamoto¹  Hisashi Onozawa¹  Tomoyuki Momma¹ 

[1] Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, Japan;

关键词: locally advanced rectal cancer;    neoadjuvant chemoradiotherapy;    predictive biomarker;    pre-treatment biopsy;    gene expression signature;    microarray;   

DOI  :  10.3390/cancers13184642

来源: DOAJ

【 摘 要 】

Background: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is widely used for patients with locally advanced rectal cancer. However, response to nCRT varies substantially among patients, highlighting the need for predictive biomarkers that can distinguish non-responsive from responsive patients before nCRT. This study aimed to build novel multi-gene assays for predicting nCRT response, and to validate our signature and previously-reported signatures in multiple independent cohorts. Methods: Three microarray datasets of pre-therapeutic biopsies containing a total of 61 non-responders and 53 responders were used as the discovery cohorts to screen for genes that were consistently associated with nCRT response. The predictive values of signatures were tested in a meta-analysis using six independent datasets as the validation cohorts, consisted of a total of 176 non-responders and 99 responders. Results: We identified four genes, including BRCA1, GPR110, TNIK, and WDR4 in the discovery cohorts. Although our 4-gene signature and nine published signatures were evaluated, they were unable to predict nCRT response in the validation cohorts. Conclusions: Although this is one of the largest studies addressing the validity of gene expression-based classifiers using pre-treatment biopsies from patients with rectal cancer, our findings do not support their clinically meaningful values to be predictive of nCRT response.

【 授权许可】

Unknown