Genetic evidence that intratumoral T-cell proliferation and activation is associated with recurrence and survival in patients with resected colorectal liver metastases
| Autor: | Leslie H. Blumgart, Simon Turcotte, Jinru Shia, Shishir K. Maithel, Hiromichi Ito, Qianxing Mo, William R. Jarnagin, Michael I. D’Angelica, Li-Xuan Qin, Yuman Fong, Ajay V. Maker, Ronald P. DeMatteo, Elliot Weisenberg |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Cancer Research Pathology medicine.medical_specialty Tumor Necrosis Factor Ligand Superfamily Member 14 Liver tumor Microarray Colorectal cancer Immunology Lymphocyte proliferation Kaplan-Meier Estimate Lymphocyte Activation Article Lymphocytes Tumor-Infiltrating Recurrence medicine Biomarkers Tumor Tumor Microenvironment Humans Survival analysis Cell Proliferation Retrospective Studies Tumor microenvironment business.industry Proportional hazards model Liver Neoplasms Middle Aged medicine.disease Survival Analysis Neoplasm Proteins Gene Expression Regulation Neoplastic Tissue Array Analysis Cancer research Immunohistochemistry Female business Colorectal Neoplasms |
| Popis: | Though immune responses correlate with prognosis in primary colorectal cancer, the role of tumor immunity in metastatic disease is less clear. We hypothesized that patient survival and tumor recurrence correlate with transcriptional evidence of lymphocyte proliferation/activation in resected colorectal cancer liver metastases (CRLM). Microarray gene analysis was performed on liver tumor specimens from 96 patients who underwent resection for CRLM. A Cox proportional hazards model identified genes associated with overall survival (OS) and recurrence-free survival (RFS). Conventional gene ontology (GO) enrichment analysis ranked biologically relevant processes. Survival probabilities of prioritized processes were assessed. Protein expression was validated with immunohistochemistry in an independent set of patients. GO analysis identified and ranked unique biologic processes that correlated with survival. Genes that specifically functioned in the biologic process of “T-cell proliferation” were significant predictors of OS (P = 0.01), and both “T-cell proliferation” and “activation” were highly associated with RFS (P ≤ 0.01). Analysis of genes in these GO categories identified increased TNFSF14/LIGHT expression to be most associated with improved OS and RFS (P ≤ 0.0006). Immunohistochemistry of an independent validation set of CRLM confirmed that both increased tumor-infiltrating lymphocytes (TIL) and higher LIGHT expression on TILs were associated with improved OS and RFS. Differential expression of genes involved in T-cell proliferation/activation was associated with survival outcomes in a large number of surgical patients who underwent resection of CRLM. These biologic functions determined by GO analysis of the tumor microenvironment have identified specific immune-related genes that may be involved in an antitumor immune response. Cancer Immunol Res; 3(4); 380–8. ©2015 AACR. |
| Databáze: | OpenAIRE |
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