Analysis of nitrogen metabolism-related gene expression in hepatocellular carcinoma to establish relevant indicators for prediction of prognosis and guidance of immunotherapy.

Abstract

Background: The prognosis of cancers is strongly connected with nitrogen metabolism (NM), which plays a critical role in the microenvironment and growth of tumors. It is unsubstantiated, however, how important NM-related genes are for the prognosis of hepatocellular carcinoma (HCC).

Methods: Using publicly available data, we examined potential mechanisms of NM-related genes in HCC, created a predictive model, and assessed immune infiltration and medication sensitivity.

Results: A prognostic model, which included 12 NM genes (COLQ, GNE, ISCU, MSRA, SARS2, SPHK1, CBS, GOT2, CHST1, EXTL2, GCLM, YARS1), was constructed based on regression analysis. The robustness of the model was validated using multiple methods. The high-risk (HR) and low-risk (LR) groups had varying degrees of immune infiltration, according to an immunology-related study. Of these, B cells and Type_II_IFN_Response were greatly infiltrated in the LR group, whereas aCDs, Macrophages, and Treg were heavily infiltrated in the HR group (p < 0.05). Because of higher immunophenoscore, the low-risk group could benefit from immunotherapy more. Drug sensitivity predictions indicated that people with high CBS expression and low GOT2 and ISCU expression may benefit more from treatment with SCH-772984, Pimasertib, Cobimetinib (isomer1), TAK-733, LY-3214996, ARRY-162, Cladribine, Fludarabine, and Hydroxyurea.

Conclusion: This work created a 12-gene signature based on NM, preliminary investigated immune infiltration in two risk categories, and discovered some possible anti-tumor medications. To sum up, our study findings offer fresh perspectives on the roles played by NM-associated genes in HCC development, prognosis, immunological response, and medication screening.