Identification of PDCD1 and PDCD1LG2 as Prognostic Biomarkers and Associated with Immune Infiltration in Hepatocellular Carcinoma.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma has been identified to be among the most prevalent malignancies in the world and has an unfavorable prognosis. Immune checkpoints perform an essential function in many biological processes and are associated with the survival of cancer patients. The function of immune checkpoints remains unknown. METHODS: We used bioinformatic methods to examine the prognostic value of immune checkpoints and the corresponding link to immune infiltration in HCC. qRT-PCR was used to validate the expression of immune checkpoints and their prognostic significance in HCC. RESULTS: The level of mRNA of SIGLEC15, PDCD1LG2, LAG3, PDCD1, CTLA4 as well as PDCD1LG2 was increased in HCC tissues as opposed to liver tissues. Immune checkpoints were shown to participate in the activation of the apoptotic pathway in HCC patients. The elevated expression of PDCD1 and PDCD1LG2 were shown to have a favorable recurrence-free survival (RFS), progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS). PDCD1, PDCD1LG2, and pT stage were independent variables that affect the HCC patients' prognoses as revealed by the multivariate and univariate analyses. A prediction nomogram indicated that the calibration plots for OS rates over three and five years had a stronger predictive performance in the TCGA HCC cohort in contrast with an ideal model. Positive correlations were observed between the PDCD1 and PDCD1LG2 expression and immune biomarkers, immune cells, chemokine receptors, as well as chemokines. CONCLUSION: The present research performed a thorough examination of the prognostic significance of immune checkpoints in HCC and its correlation with immune infiltration, which suggested that PDCD1 and PDCD1LG2 were prognostic biomarkers in HCC and related to the immune infiltration.