AIM: Patients with rectal cancer who achieve a complete pathological response after preoperative chemoradiation (CRT) have an improved oncological outcome. Identifying factors associated with a lack of response could help our understanding of the underlying biology of treatment resistance. This study aimed to develop a gene expression signature for CRT-resistant rectal cancer using high-throughput nucleotide microarrays. METHOD: Pretreatment biopsies of rectal adenocarcinomas were prospectively collected and freshly frozen according to an institutional review board-approved protocol. Total tumour mRNA was extracted and gene expression levels were measured using microarrays. Patients underwent proctectomy after completing standard long-course CRT and the resected specimens were graded for treatment response. Gene expression profiles for nonresponders were compared with those of responders. Differentially expressed genes were analyzed for functional significance using the Ingenuity Pathway Analysis (IPA) software. RESULTS: Thirty-three patients treated between 2006 and 2009 were included. We derived 812-gene and 183-gene signatures separating nonresponders from responders. The classifiers were able to identify nonresponders with a sensitivity and specificity of 100% using the 812-gene signature, and sensitivity and specificity of 33% and 100% using the 183-gene signature. IPA canonical pathway analysis revealed a significant ratio of differentially expressed genes in the 'DNA double-strand break repair by homologous recombination' pathway. CONCLUSION: Certain rectal cancer gene profiles are associated with poor response to CRT. Alterations in the DNA double-strand break repair pathway could contribute to treatment resistance and provides an opportunity for further studies. Colorectal Disease
AIM: Patients with rectal cancer who achieve a complete pathological response after preoperative chemoradiation (CRT) have an improved oncological outcome. Identifying factors associated with a lack of response could help our understanding of the underlying biology of treatment resistance. This study aimed to develop a gene expression signature for CRT-resistant rectal cancer using high-throughput nucleotide microarrays. METHOD: Pretreatment biopsies of rectal adenocarcinomas were prospectively collected and freshly frozen according to an institutional review board-approved protocol. Total tumour mRNA was extracted and gene expression levels were measured using microarrays. Patients underwent proctectomy after completing standard long-course CRT and the resected specimens were graded for treatment response. Gene expression profiles for nonresponders were compared with those of responders. Differentially expressed genes were analyzed for functional significance using the Ingenuity Pathway Analysis (IPA) software. RESULTS: Thirty-three patients treated between 2006 and 2009 were included. We derived 812-gene and 183-gene signatures separating nonresponders from responders. The classifiers were able to identify nonresponders with a sensitivity and specificity of 100% using the 812-gene signature, and sensitivity and specificity of 33% and 100% using the 183-gene signature. IPA canonical pathway analysis revealed a significant ratio of differentially expressed genes in the 'DNA double-strand break repair by homologous recombination' pathway. CONCLUSION: Certain rectal cancer gene profiles are associated with poor response to CRT. Alterations in the DNA double-strand break repair pathway could contribute to treatment resistance and provides an opportunity for further studies. Colorectal Disease
Authors: Sylvain Ferrandon; Jennifer DeVecchio; Leonardo Duraes; Hanumant Chouhan; Georgios Karagkounis; Jacqueline Davenport; Matthew Orloff; David Liska; Matthew F Kalady Journal: Cancer Res Date: 2019-11-08 Impact factor: 12.701
Authors: Theodore S Hong; Eliezer M Van Allen; Sophia C Kamran; Jochen K Lennerz; Claire A Margolis; David Liu; Brendan Reardon; Stephanie A Wankowicz; Emily E Van Seventer; Adam Tracy; Jennifer Y Wo; Scott L Carter; Henning Willers; Ryan B Corcoran Journal: Clin Cancer Res Date: 2019-06-28 Impact factor: 12.531
Authors: Pablo Palma; Carlos Cano; Raquel Conde-Muiño; Ana Comino; Pablo Bueno; J Antonio Ferrón; Marta Cuadros Journal: PLoS One Date: 2014-11-07 Impact factor: 3.240
Authors: Raquel Conde-Muíño; Marta Cuadros; Natalia Zambudio; Inmaculada Segura-Jiménez; Carlos Cano; Pablo Palma Journal: Biomed Res Int Date: 2015-10-04 Impact factor: 3.411