Comprehensive evaluation of the effectiveness of gene expression signatures to predict complete response to neoadjuvant chemoradiotherapy and guide surgical intervention in rectal cancer

Author(s):Show less -

Lopes-Ramos, Camila ^[1] ; Koyama, Fernanda C. ^{[1, 2]} ; Habr-Gama, Angelita ^{[3, 4]} ; Salim, Anna Christina M. ^[2] ; Bettoni, Fabiana ^[1] ; Asprino, Paula F. ^[1] ; Franca, Gustavo S. ^{[1, 5]} ; Gama-Rodrigues, Joaquim ^{[3, 4]} ; Parmigiani, Raphael B. ^[1] ; Perez, Rodrigo O. ^{[4, 2, 6]} ; Galante, Pedro A. F. ^[1] ; Camargo, Anamaria A. ^{[1, 2]}

Affiliation

^[1] Hosp Sirio Libanes, Ctr Mol Oncol, Sao Paulo - Brazil

^[2] Ludwig Inst Canc Res, Sao Paulo Branch, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Sch Med, Sao Paulo - Brazil

^[4] Angelita & Joaquim Gama Inst, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Dept Biochem, Sao Paulo - Brazil

^[6] Univ Sao Paulo, Sch Med, Colorectal Surg Div, Sao Paulo - Brazil

• Document type: Journal article
• Source: CANCER GENETICS; v. 208, n. 6, p. 319-326, JUN 2015.
• Web of Science Citations: 21

Abstract

Neoadjuvant chemoradiotherapy (nCRT) may lead to complete tumor regression in rectal cancer patients. Prediction of complete response to nCRT may allow a personalized management of rectal cancer and spare patients from unnecessary radical total mesorectal excision with or without sphincter preservation. To identify a gene expression signature capable of predicting complete pathological response (pCR) to nCRT, we performed a gene expression analysis in 25 pretreatment biopsies from patients who underwent 5FU-based nCRT using RNA-Seq. A supervised learning algorithm was used to identify expression signatures capable of predicting pCR, and the predictive value of these signatures was validated using independent samples. We also evaluated the utility of previously published signatures in predicting complete response in our cohort. We identified 27 differentially expressed genes between patients with pCR and patients with incomplete responses to nCRT. Predictive gene signatures using subsets of these 27 differentially expressed genes peaked at 81.8% accuracy. However, signatures with the highest sensitivity showed poor specificity, and vice-versa, when applied in an independent set of patients. Testing previously published signatures on our cohort also showed poor predictive value. Our results indicate that currently available predictive signatures are highly dependent on the sample set from which they are derived, and their accuracy is not superior to current imaging and clinical parameters used to assess response to nCRT and guide surgical intervention. (AU)

• FAPESP's process: 11/50684-8 - Neoadjuvant treatment in rectal cancer: identification of a genic signature capable of predicting response to treatment and the development of personalized biomarkers for assessing minimal residual disease
• Grantee: Anamaria Aranha Camargo
• Support Opportunities: Regular Research Grants