Locally advanced rectal cancer transcriptomic-based secretome analysis reveals novel biomarkers useful to identify patients according to neoadjuvant chemoradiotherapy response

Author(s):Show less -

do Canto, Luisa Matos ^{[1, 2]} ; Cury, Sarah Santiloni ^[3] ; Barros-Filho, Mateus Camargo ^[1] ; Catin Kupper, Bruna Elisa ^[4] ; Ferreira de Souza Begnami, Maria Dirlei ^[5] ; Scapulatempo-Neto, Cristovam ^{[6, 7]} ; Carvalho, Robson Francisco ^[3] ; Marchi, Fabio Albuquerque ^[1] ; Olsen, Dorte Aalund ^[8] ; Madsen, Jonna Skov ^{[9, 10, 8]} ; Havelund, Birgitte Mayland ^{[9, 11]} ; Aguiar, Jr., Samuel ^[4] ; Rogatto, Silvia Regina ^{[2, 9, 10]}

Affiliation:Show less -

^[1] AC Camargo Canc Ctr, Int Res Ctr CIPE, BR-04002010 Sao Paulo - Brazil

^[2] Univ Hosp Southern Denmark, Dept Clin Genet, DK-7100 Vejle - Denmark

^[3] Sao Paulo State Univ UNESP, Dept Morphol, Inst Biosci, BR-18618689 Botucatu, SP - Brazil

^[4] AC Camargo Canc Ctr, Dept Pelv Surg, BR-04002010 Sao Paulo - Brazil

^[5] AC Camargo Canc Ctr, Dept Pathol, BR-04002010 Sao Paulo - Brazil

^[6] Mol Oncol Res Ctr, Barretos - Brazil

^[7] Diagnost Amer DASA, Sao Paulo - Brazil

^[8] Univ Hosp Southern Denmark, Dept Biochem & Immunol, DK-7100 Vejle - Denmark

^[9] Danish Colorectal Canc Ctr South, DK-7100 Vejle - Denmark

^[10] Univ Southern Denmark, Inst Reg Hlth Res, Fac Hlth Sci, DK-7100 Vejle - Denmark

^[11] Univ Hosp Southern Denmark, Dept Oncol, DK-7100 Vejle - Denmark

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 9, JUN 18 2019.
• Web of Science Citations: 1

Abstract

Most patients with locally advanced rectal cancer (LARC) present incomplete pathological response (pIR) to neoadjuvant chemoradiotherapy (nCRT). Despite the efforts to predict treatment response using tumor-molecular features, as differentially expressed genes, no molecule has proved to be a strong biomarker. The tumor secretome analysis is a promising strategy for biomarkers identification, which can be assessed using transcriptomic data. We performed transcriptomic-based secretome analysis to select potentially secreted proteins using an in silico approach. The tumor expression profile of 28 LARC biopsies collected before nCRT was compared with normal rectal tissues (NT). The expression profile showed no significant differences between complete (pCR) and incomplete responders to nCRT. Genes with increased expression (pCR = 106 and pIR = 357) were used for secretome analysis based on public databases (Vesiclepedia, Human Cancer Secretome, and Plasma Proteome). Seventeen potentially secreted candidates (pCR =1, pIR = 13 and 3 in both groups) were further investigated in two independent datasets (TCGA and GSE68204) confirming their over-expression in LARC and association with nCRT response (GSE68204). The expression of circulating amphiregulin and cMET proteins was confirmed in serum from 14 LARC patients. Future studies in liquid biopsies could confirm the utility of these proteins for personalized treatment in LARC patients. (AU)

• FAPESP's process: 14/06323-9 - Molecular markers identification of neoadjuvant treatment response in rectal adenocarcinoma patients
• Grantee: Luisa Matos Do Canto Alvim
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 15/25803-4 - Integrative (genomic, transcriptomic and methylome) analyses of rectal cancer to unravel predictors of neoadjuvant treatment response
• Grantee: Luisa Matos Do Canto Alvim
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• FAPESP's process: 08/57887-9 - National Institute of Oncogenomics
• Grantee: Luiz Paulo Kowalski
• Support Opportunities: Research Projects - Thematic Grants