Prognostic Value of Expression of PD-1 and CTLA-4 in Peripheral Blood in Patients with Hepatocellular Carcinoma

초록

Background/Aims Hepatocellular carcinoma (HCC) is the second most prevalent cause of cancer-related death worldwide. The poor prognosis of HCC is attributed to the lack of abiomarker that can effectively predict patients' responses to various treatments. Inthis study, we investigated the potential of programmed death 1 (PD-1) and cytotoxicT-lymphocyte- associated protein 4 (CTLA-4) gene expressions in peripheral bloodmononuclear cells (PBMCs) as prognostic biomarkers for HCC. Methods This study was approved by an institutional review board of Chungnam national University Hospital, Daejeon, Korea (CNUH- 2020-10-08). The buffy coat was excepted from EL buffer for erythrocytes lysis, and was treated with 20 μl proteinase, andmixed with 200 μl lysis buffer. The samples were incubated at 57oC for 15 min, then,reacted with 200 μl of ethanol. Results Neither CTLA-4 nor PD-1 gene expression in PBMCs was associated with the patients' tumor size, multifocality, and modified UICC stages. Specifically, the AUROC valuesfor determining HCC patients with tumor sizes larger than the average, multifocaltumors, and high modified UICC tumor stages (> 2) were all less than 0.720 (p > 0.05).Nevertheless, both genes were strongly associated with patients' outcomes. AKaplan-Meier survival analysis revealed that patients with low CTLA-4 gene expressions (≤ median) exhibited a 1.51-fold (p = 0.022) longer mean overall survival(OS) than those with high CTLA-4 gene expressions. Moreover, PD-1 gene expressions demonstrated an even higher predictive value in estimating HCC patients' survival. None of the patients with low PD-1 gene expressions (≤ median)died during this study, while patients with high PD-1 expressions showed a poor OSof 36.0 ± 9.0 months (p<0.001). Interestingly,