Use of T-cell proliferation to predict survival and recurrence in patients with resected colorectal liver metastases.

Abstract

10571 Background: Immune responses correlate with prognosis in primary colorectal cancer. The role tumor immunity has in metastatic disease is less clear. We hypothesize that patient survival and tumor recurrence correlate with lymphocyte proliferation in resected colorectal liver metastases (CRLM). Methods: Microarray gene analysis was performed on viable liver tumor specimens from 96 patients who underwent liver resection for CRLM from 2000-2007. A Cox proportional hazards model was utilized to identify genes associated with overall survival (OS), recurrence-free survival (RFS), and liver specific RFS. Gene ontology (GO) enrichment analysis of these significant genes was used to rank biologically relevant processes using the EASE software. For significant immunologic genes on GO analysis, survival probabilities were assessed using the Kaplan-Meier method. Results: Liver recurrence developed in 45 patients (47%), and 39 patients (41%) died of disease during a median follow-up period of 30 months. GO analysis identified and ranked unique biologic processes that significantly correlated with OS, RFS and liver RFS. Differential expression of genes that specifically function in T-cell proliferation were significant predictors of OS and liver RFS, and the most significant predictor of RFS (#1 of 309 biologic processes, p = 0.002). Specific immunologic gene analysis determined that high tumor expression of the genes TNFSF14/LIGHT, IL10, IL18, and low expression of NCK1 was associated with improved OS, RFS, and liver RFS (p < 0.0006). These genes were not found to be significantly associated with other clinical predictors of survival (size of primary, primary node status, CEA, disease free interval, or number of CRLM), or the administration of preoperative chemotherapy. Conclusions: We have identified an immune profile of genes (LIGHT, IL10, IL18, and NCK1) that function in T-cell proliferation and that are associated with survival and disease recurrence in patients who undergo resection of CRLM. This study genetically characterizes the immunologic milieu of CRLM and has identified markers of the anti-tumor immune response for further validation studies. No significant financial relationships to disclose.