Abstract
Prostate cancer (PCa) is a malignancy that affects men and is characterized by metastasis and high rates of morbidity. The objective of this study was to explore novel PCa biomarker with potential diagnostic and therapeutic value and relationships between it and tumor immunity and development. A total of 32 key genes were screened out via LASSO based upon 188 intersection genes obtained from WGCNA and DEGs analysis in GSE32571, and PPP1R14B was further identified by COX regression based on the TCGA database and validated by qRT-PCR. Although it has been reported that PPP1R14B may have a certain correlation with the prognosis of uterine corpus endometrial carcinoma, breast cancer and gastrointestinal cancer, there are none of studies about correlation between PPP1R14B and PCa. Predictive ability analysis showed that PPP1R14B had greatly predictive values in occurrence and prognosis of PCa. Immune analysis revealed that overexpression of PPP1R14B was related to the increase of ALKBH2, UCK2, RAC3 and RAB17 and the decrease of CD40, DKK3, COL17A1 and PGRMC1, which would result in downregulation of plasma cells, upregulation of T regulatory cells and disorder of macrophage proportion to suppress adaptive immune directed against PCa. GSEA analysis showed that PPP1R14B, as an inhibitor of PP1, its overexpression was mainly involved in regulating pathways associated with MYC, E2F, PFN1 and so on, which was participated in the regulation of immune factors such as CD40, RAC3, COL17A, DKK3, as well as biological processes such as proliferation and migration. Patients with higher PPP1R14B expression responded more sensitively to drugs selumetinib and vorinostat, zebularine, azacitidine and VER155008. In summary, PPP1R14B was a potential diagnostic and prognostic biomarker of PCa and its high expression had closely association with tumor immune inhibition, proliferation and migration, providing a new target for drug therapy and immunotherapy in PCa.