EXTL3 could serve as a potential biomarker of prognosis and immunotherapy for prostate cancer and its potential mechanisms

Pingan Chang, Shenglan Chen, Xiumei Chang, Jiaxi Zhu, Qingsheng Tang, Limin Ma

Exostosin like glycosyltransferase 3 (EXTL3) had been reported to be associated with immune deficiency and play prognostic roles in various cancers. However, little is known about the associations between EXTL3 and prostate cancer (PCa). Hence, this article was designed to clarify their associations. All original data were downloaded from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) and CellMiner database was utilized, respectively, to identify EXTL3-related signaling pathways and drugs. We explored the relationships between EXTL3 expression and immunity to further evaluate the involvement of EXTL3 in response to immunotherapies. LncRNA/RBP/EXTL3 mRNA networks were also identified for its potential mechanism. Compared with normal prostate samples, EXTL3 was poorly expressed in PCa samples not only in mRNA expression levels, but also in protein expression levels, with worse overall survival (P < 0.05) and this gene could be an independent prognostic biomarker for PCa (both P < 0.05). EXTL3 was revealed to be markedly linked with seven signaling pathways in PCa by GSEA, including calcium, chemokine, ERBB, JAK STAT, MAPK, WNT, oxidative phosphorylation pathways. EXTL3 expression was also revealed to be significantly associated with MSI, immune cells, immune checkpoint molecules, tumor microenvironment and immune cells infiltration. We further predicted immune responses of EXTL3 gene to immunotherapies by TIDE database and the IMvigor210 cohort. A total of six LncRNA/RBP/EXTL3 mRNA networks were eventually identified for its potential mechanisms. EXTL3 could serve as a potential biomarker of prognosis and immunotherapy for PCa and six LncRNA/RBP/EXTL3 mRNA networks were also identified for its potential mechanisms.