Transcriptional Landscape of PD-1, PD-L1 and PD-L2 Correlated Genes and Their Association with Mutation, Immune Infiltration and Clinical Outcomes of Hepatocellular Carcinoma

The immune checkpoint of PD-1/PD-L1/PD-L2 has been suggested to be an effective target of immunotherapy in a variety types of cancer. However, the potential regulating network of PD-1/PD-L1/PD-L2 signaling in immune escape still remains unclear in hepatocellular carcinoma (HCC). Based on transcriptional data of hepatocellular carcinoma from TCGA. The role of PD-1/PD-L1/PD-L2 in determination of clinical were analysed. The relationship between mutation and PD gene were analysed. PD-1/PD-L1/PD-L2 correlated genes were screened by WGCNA analysis and the biological process of certain genes were enriched. Relation of PD1/PD-L1/PD-L2 with immune infiltration and checkpoints were investigated by co-expression analysis. Clinically, PD-1 and PD-L2 expressions were correlated with recurrence (both P= 0.005) but no significant correlation was found between PD-1/PD-L1/PD-L2 and HCC survival. Mutations of CACNA1E, CTNNB1, RYR2, TP53 and TTN altered PD-1/PD-L1/PD-L2 expression profiles in HCC. PD-1/PD-L1/PD-L2 correlated genes mainly enriched in biological process of T cell activation and cell-cell adhesion. In addition, PD-1/PD-L1/PD-L2 was related with immune infiltration of CD8 T cells, and cytotoxic lymphocytes. Immune checkpoints of CTLA4, CD27, CD80, CD86, CD28 significantly correlated with PD-1/PD-L1/PD-L2 axis. Funding Statement: This study is supported by grants from the National Science and Technology Major Project (2017ZX10201201;2017ZX10202202);Liaoning Province Natural Science Foundation [20180550096] Declaration of Interests: All of the authors declare that there is no conflict of interest. Ethics Approval Statement: Not required.