Pan-Cancer Analysis of PIMREG as a Biomarker for the Prognostic and Immunological Role

Abstract

Phosphatidylinositol binding clathrin assembly protein interacting mitotic regulator (PIMREG) localizes to the nucleus and can significantly elevate the nuclear localization of clathrin assembly lymphomedullary leukocythemia gene. Although there is some evidence to support an important action for PIMREG in the occurrence and development of certain cancers, currently no pan-cancer analysis of PIMREG is available. Therefore, we intended to estimate the prognostic predictive value of PIMREG and to explore its potential immune function in 33 cancer types. By using a series of bioinformatics approaches, we extracted and analyzed datasets from Oncomine, The Cancer Genome Atlas, Cancer Cell Lineage Encyclopedia (CCLE) and the Human Protein Atlas (HPA), to explore the underlying carcinogenesis of PIMREG, including relevance of PIMREG to prognosis, microsatellite instability (MSI), tumor mutation burden (TMB), tumor microenvironment (TME) and infiltration of immune cells in various types of cancer. Our findings indicate that PIMREG is highly expressed in at least 24 types of cancer, and is negatively correlated with prognosis in major cancer types. In addition, PIMREG expression was correlated with TMB in 24 cancers and with MSI in 10 cancers. We revealed that PIMREG is co-expressed with genes encoding major histocompatibility complex, immune activation, immune suppression, chemokine and chemokine receptors. We also found that the different roles of PIMREG in the infiltration of different immune cell types in different tumors. PIMREG can potentially influence the etiology or pathogenesis of cancer by acting on immune-related pathways, chemokine signaling pathway, regulation of autophagy, RIG-I like receptor signaling pathway, antigen processing and presentation, FC epsilon RI pathway, complement and coagulation cascades, T cell receptor pathway, NK cell mediated cytotoxicity and other immune-related pathways. Our study suggests that PIMREG can be applied as a prognostic marker in a variety of malignancies because of its role in tumorigenesis and immune infiltration.

The Hypoxia-Related Gene COL5A1 Is a Prognostic and Immunological Biomarker for Multiple Human Tumors

“…Immunotherapy or targeted therapy is now more and more used for a variety of tumor patients, particularly ICB therapy for patients with unsatisfactory radiotherapy and chemotherapy [ 20 ]. Therefore, it is necessary to preliminarily reveal the value of COL5A1 in predicting drug sensitivity and immunotherapy sensitivity of tumor cells through biological methods.…”

“…Oncomine ( https://www.oncomine.org/ ), an online cancer microarray database [ 19 ], was employed to analyze the COL5A1 expression in 33 human tumors as we used to do [ 20 ]. We downloaded mRNA expression data and clinical information from the UCSC Xena website ( https://xena.ucsc.edu/ ).…”

“…The correlation of COL5A1 with TMB or MSI was analyzed as previously described [ 6 , 20 ]. We also applied cBioPortal to investigate the correlation between COL5A1 mutations and prognosis.…”

“…We employed the ESTIMATE algorithm and the R packages “estimate” and “limma” to evaluate immune and stromal scores [ 21 ] as we used to [ 6 , 20 , 22 ]. For more reliable immune score evaluation, we then employed the “immuneeconv” R package that integrated the six algorithms, including TIMER, xCell, MCP-counter, CIBERSORT, EPIC, and quanTIseq.…”

“…Gene Ontology (GO) and Kyoto Encyclopedia of Genes analyses and Genomes (KEGG) and the coexpression of COL5A1 with immune checkpoint genes and immune-related genes were conducted as we described previously [ 6 , 20 ].…”