Development and Validation of an Immune Microenvironment Based Prognostic Signature and Signal Pathways in Prostate Cancer

Abstract

Background: The study of the PCa immune microenvironment has brought new opportunities for the clinical diagnosis and treatment of PCa, but the current study has failed to obtain satisfactory results. We aim to develop a generalized, individualized immune prognostic signature that can improve the survival rate of patients.Methods: We collected a total of 591 sample data from the TCGA and GEO cohorts, and evaluated the abundance and distribution of immune cell members in the mixed cell population in the gene expression matrix by CIBERSORT, ESTIMATE, ssGSEA, and other methods. Calculate the TMB value of the mutant gene to evaluate the reliability of PCa for immunotherapy. Besides, the genes related to the immune microenvironment and mutation load of PCa are obtained, and the target genes are obtained by the intersection with the immune-related genes in the ImmPort database. And perform pan-cancer analysis of the target gene to evaluate the immunological commonality and biological pathways in a variety of cancers. Finally, a Western blot experiment was used to explore the mechanism of the target gene in PCa immune microenvironment.Results: We found that M0, M2, and Mast cell sresting differed significantly between prostate cancer and normal tissue and that patients with low plasma cell abundance were more likely to develop lymph node metastasis. LTF, as a core gene, is closely related to changes in the immune microenvironment of PCa, and its low expression in tumors promotes primary immune deficiency, cancer development, and enrichment in the JAK/STAT signaling pathway. Cell experiments found that LTF overexpression reduces tumor-derived GM-CSF secretion by inhibiting JAK/STAT pathway, achieving the purpose of regulating tumor immune microenvironment and inhibiting PCa cell proliferation and migration.Conclusions: The proposed clinical-immune signature and core gene is the most promising biomarkers for improving the overall survival rate of PCa. It has been verified that overexpression of LTF reduces the secretion of tumor-derived GM-CSF by inhibiting the JAK/STAT pathway.