2026-04-13T02:16:13Zhttps://recercat.cat/oai/request
oai:recercat.cat:2445/1760952025-12-05T12:04:12Zcom_2072_1057col_2072_478916col_2072_478917col_2072_478921
RECERCAT author Kamal, Yasmin author Dwan, Dennis author Hoehn, Hannah J. author Sanz Pamplona, Rebeca author Alonso Aguado, Maria Henar author Moreno Aguado, Víctor author Cheng, Chao author Schell, Michael J. author Kim, Youngchul author Felder, Seth I. author Rennert, Hedy S. author Melas, Marilena author Lazaris, Charalampos author Bonner, Joseph D. author Siegel, Erin M. author Shibata, David author Rennert, Gad author Gruber, Stephen B. author Frost, H. Robert author Amos, Christopher I. author Schmit, Stephanie L. 2021-04-08T15:31:25Z2021-04-08T15:31:25Z2021-01-012021-04-08T07:52:14Z A substantial fraction of patients with stage I-III colorectal adenocarcinoma (CRC) experience disease relapse after surgery with curative intent. However, biomarkers for predicting the likelihood of CRC relapse have not been fully explored. Therefore, we assessed the association between tumor infiltration by a broad array of innate and adaptive immune cell types and CRC relapse risk. We implemented a discovery-validation design including a discovery dataset from Moffitt Cancer Center (MCC; Tampa, FL) and three independent validation datasets: (1) GSE41258 (2) the Molecular Epidemiology of Colorectal Cancer (MECC) study, and (3) GSE39582. Infiltration by 22 immune cell types was inferred from tumor gene expression data, and the association between immune infiltration by each cell type and relapse-free survival was assessed using Cox proportional hazards regression. Within each of the four independent cohorts, CD4+ memory activated T cell (HR: 0.93, 95% CI: 0.90-0.96; FDR = 0.0001) infiltration was associated with longer time to disease relapse, independent of stage, microsatellite instability, and adjuvant therapy. Based on our meta-analysis across the four datasets, 10 innate and adaptive immune cell types associated with disease relapse of which 2 were internally validated using multiplex immunofluorescence. Moreover, immune cell type infiltration was a better predictors of disease relapse than Consensus Molecular Subtype (CMS) and other expression-based biomarkers (Immune-AICMCC:238.1-238.9; CMS-AICMCC: 241.0). These data suggest that transcriptome-derived immune profiles are prognostic indicators of CRC relapse and quantification of both innate and adaptive immune cell types may serve as candidate biomarkers for predicting prognosis and guiding frequency and modality of disease surveillance. cc by-nc (c) Kamal et al., 2021 http://creativecommons.org/licenses/by-nc/3.0/es/ info:eu-repo/semantics/openAccess Càncer colorectal Metàstasi Colorectal cancer Metastasis Tumor immune infiltration estimated from gene expression profiles predicts colorectal cancer relapse info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion