NAPSB as a predictive marker for prognosis and therapy associated with an immuno-hot tumor microenvironment in hepatocellular carcinoma NAPSB predicts prognosis and therapy in HCC

Background: Napsin B Aspartic Peptidase, Pseudogene (NAPSB) was associated with CD4 + T cell infiltration in pancreatic ductal adenocarcinoma. But the biological role of NAPSB in hepatocellular carcinoma (HCC) remains to be determined. Methods The expression of NAPSB in pan-cancer and HCC as well as its clinicopathological association were analyzed using data from several public datasets. qRT-PCR was used to verify the relative expression of NAPSB in HCC using Zhongnan cohort. Kaplan-Meier analyses, univariate and multivariate Cox regression were conducted to determine the predictive value of NAPSB on HCC prognosis. Then enrichment analyses were performed to identify the possible biological functions of NAPSB. Subsequently, the immunological characteristics of NAPSB in the HCC tumor microenvironment (TME) were demonstrated comprehensively. The role of NAPSB in predicting hot tumors and its impact on immunotherapy and chemotherapy responses was also analyzed. Results NAPSB was downregulated in HCC and high NAPSB expression showed an improved survival outcome. Enrichment analyses showed that NAPSB was related to immune activation. NAPSB was positively correlated with immunomodulators, tumor-infiltrating immune cells (TIICs), T cell inflamed score, and cancer immunity cycles and highly expressed in immuno-hot tumors. High expression of NAPSB was sensitive to immunotherapy and chemotherapy, possibly due to its association with pyroptosis, apoptosis and necrosis (PANoptosis). Conclusions NAPSB was correlated with an immuno-hot and inflamed TME and tumor cell death. It can be utilized as a promising predictive marker for prognosis and therapy in HCC.