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http://hdl.handle.net/2445/118783
Title: | Mutanome and expression of immune response genes in microsatellite stable colon cancer |
Author: | Sanz Pamplona, Rebeca Gil Hoyos, Raúl López Dóriga Guerra, Adriana Alonso Aguado, Maria Henar Aussó, Susanna Garcia i Molleví, David Santos, Cristina Sanjuan, Xavier Salazar Soler, Ramón Alemany Bonastre, Ramon Moreno Aguado, Víctor |
Keywords: | Càncer colorectal Pronòstic mèdic Mutació (Biologia) Genètica Colorectal cancer Prognosis Mutation (Biology) Genetics |
Issue Date: | Apr-2016 |
Publisher: | Impact Journals |
Abstract: | The aim of this study was to analyze the impact of the mutanome in the prognosis of microsatellite stable stage II CRC tumors. The exome of 42 stage II, microsatellite stable, colon tumors (21 of them relapse) and their paired mucosa were sequenced and analyzed. Although some pathways accumulated more mutations in patients exhibiting good or poor prognosis, no single somatic mutation was associated with prognosis. Exome sequencing data is also valuable to infer tumor neoantigens able to elicit a host immune response. Hence, putative neoantigens were identified by combining information about missense mutations in each tumor and HLAs genotypes of the patients. Under the hypothesis that neoantigens should be correctly presented in order to activate the immune response, expression levels of genes involved in the antigen presentation machinery were also assessed. In addition, CD8A level (as a marker of T-cell infiltration) was measured. We found that tumors with better prognosis showed a tendency to generate a higher number of immunogenic epitopes, and up-regulated genes involved in the antigen processing machinery. Moreover, tumors with higher T-cell infiltration also showed better prognosis. Stratifying by consensus molecular subtype, CMS4 tumors showed the highest association of expression levels of genes involved in the antigen presentation machinery with prognosis. Thus, we hypothesize that a subset of stage II microsatellite stable CRC tumors are able to generate an immune response in the host via MHC class I antigen presentation, directly related with a better prognosis. |
Note: | Reproducció del document publicat a: https://doi.org/10.18632/oncotarget.7293 |
It is part of: | Oncotarget, 2016, vol. 7, num. 14, p. 17711-17725 |
URI: | http://hdl.handle.net/2445/118783 |
Related resource: | https://doi.org/10.18632/oncotarget.7293 |
ISSN: | 1949-2553 |
Appears in Collections: | Articles publicats en revistes (Ciències Clíniques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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