AUTHOR=Chen Chen , Shang Anquan , Gao Yuting , Huang Jingjuan , Liu Gege , Cho William C. , Li Dong 

TITLE=PTBPs: An immunomodulatory-related prognostic biomarker in pan-cancer

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2022.968458

DOI=10.3389/fmolb.2022.968458

ISSN=2296-889X

ABSTRACT=<p><bold>Background:</bold> The polypyrimidine tract-binding protein (PTBP) nuclear ribonucleoprotein family of proteins, including PTBP1, PTBP2 and PTBP3, regulate the process of cell proliferation, differentiation, apoptosis and carcinogenesis. PTBPs exhibit oncogenic effects in certain tumors. However, the role of PTBPs in pan-cancer remains unclear. Our study examined the clinical significance and mechanism of PTBPs in pan-cancer.</p><p><bold>Methods:</bold> We compared the expression of <italic>PTBPs</italic> in paired and unpaired tissue samples from the Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression, Kaplan–Meier curves, and time-dependent receiver operating characteristic (ROC) curves were used to assess the prognostic significance of <italic>PTBPs</italic> in pan-cancer. The cBioPortal database also identified genomic abnormalities in <italic>PTBPs</italic>. TISIDB, TCGA, and Cellminer were used to investigate the relationship between <italic>PTBP</italic> expression and immune subtypes, immune checkpoint (ICP) genes, tumor mutational burden (TMB), microsatellite instability (MSI), tumor-infiltrating immune cells, and chemosensitivity. cBioPortal was used to search for <italic>PTBP</italic> co-expressing genes in pan-cancer, and GO and KEGG enrichment analyses were performed to search for <italic>PTBP</italic>-related signaling pathways.</p><p><bold>Results:</bold><italic>PTBPs</italic> were shown to be widely upregulated in human tumor tissues. <italic>PTBP1</italic> showed good prognostic value in ACC, KIRP, and LGG; <italic>PTBP2</italic> in ACC and KICH; and <italic>PTBP3</italic> in ACC, LGG, and PAAD, with AUC &gt;0.7. <italic>PTBPs</italic> were differentially expressed in tumor immune subtypes and had a strong correlation with tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment (TME). In addition, <italic>PTBP</italic> expressions were related to ICP, TMB, and MSI, suggesting that these three PTBPs may be potential tumor immunotherapeutic targets and predict the efficacy of immunotherapy. Enrichment analysis of co-expressed genes of <italic>PTBPs</italic> showed that they may be involved in alternative splicing, cell cycle, cellular senescence, and protein modification.</p><p><bold>Conclusion:</bold> PTBPs are involved in the malignant progression of tumors. <italic>PTBP1</italic>, <italic>PTBP2</italic> and <italic>PTBP3</italic> may be potential biomarkers for prognosis and immunotherapy in pan-cancer and may be novel immunotherapeutic targets.</p>