Transcripts of immune cell surface proteins from tumor samples to predict patient clinical outcome.

Abstract

32 Background: Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide, and its incidence and mortality are rapidly increasing in the US. Treatments for advanced HCC are limited despite best efforts to develop therapeutics that target the deregulated pathways of HCC. Recent studies reveal a direct causal relationship between cancer and immune dysfunction, whereby tumor cells and their microenvironment can evade immune attack by exploiting various immunoregulatory mechanisms in a process termed cancer immune editing. This study objective is to determine the relationship between immune cell surface protein transcripts from tumor samples and the clinical outcome of pts by performing exploratory analyses of liver cancer data from the cancer genome atlas (TCGA). Methods: We analyzed RNAseq data from a cohort of 75 HCC samples in the TCGA collection. We explored the association of expression of a group of specific markers for infiltrating lymphocytes (several subtypes) with overall survival (OS) and tumor immune infiltrates (IHC data). Results: Among the 75 HCC cases analyzed, 25 pts had Hepatitis C (HCV), 25 had Hepatitis B (HBV), and 25 had HCV and HBV co-infection. Fourteen of the 75 cases were found to express the CD8B isoform. The LOG RANK survival test showed a significant association between CD8B level and OS (ChiSq = 5.2, 1df; p= 0.0222), as did the Cox proportional hazard model for survival. The latter test showed that pts who’s HCC did not express the CD8B were at higher risk of death compared with those who did. Additional immune cell subtype specific transcripts are being tested. Based on analysis of differentially expressed genes between immune cell subtype "Low" and vs. "High" groups, pathways highly relevant to lymphocyte signaling and immune response and infiltration are identified. Conclusions: Immune cell specific transcripts in tumor samples may serve as a predictor of response to treatments that target immune evasion in cancer pts.