Comprehensive Analysis of RELL2 as a Potential Biomarker Associated with Tumor Immune Infiltrating Cells in a Pan-Cancer Analysis

Abstract

Background. Receptor expressed in lymphoid tissues-like 2 (RELL2), which is a member of RELT family, is closely associated with the plasma membrane and acts as a modulator for RELT signaling. Overexpression of RELL2 induces the activation of MAPK14/p38 cascade and apoptosis. However, whether RELL2 contributes to cancers remains unclear. Here, we examined its role in cancer patient prognosis and various tumors. Methods. We used several bioinformatics methods, specifically gene set enrichment analysis (GSEA), ScanNeo, and ESTIMATE, to analyze the CCLE dataset, GTEx dataset, and TCGA dataset. We investigated the possible association of RELL2 with the microsatellite instability (MSI) of various tumors, tumor mutational burden (TMB), immune checkpoint, immune neoantigens, immune microenvironment, and patient prognosis. Result. RELL2 is highly expressed in cancer compared with normal tissues. RELL2 expression is linked with worse progression-free interval and overall survival in numerous cancers. In most cancers, high RELL2 expression was related to a poor prognosis. RELL2 expression was significantly associated with the tumor microenvironment, MSI, and TMB. RELL2 expression is strongly associated with phenotypes that are of major clinical significance, particularly those associated with immune neoantigens and the expression profiles of immune checkpoint genes in pan-cancer. RELL2 expression strongly linked with the expressions of methyltransferases and DNA repair genes. It also significantly correlated with multiple signaling pathways through gene set enrichment analysis. Conclusion. RELL2 may be a prognostic biomarker in pan-cancer and may have an important function in tumorigenesis and progression.

Comprehensive analysis of TLX2 in pan cancer as a prognostic and immunologic biomarker and validation in ovarian cancer

“…In recent years, the use of immunotherapy as a modern cancer treatment has been expanding in clinical applications 11 . Anticancer immunotherapy has encountered its own opportunities, with several reports identifying biomarkers for immune checkpoint inhibitors (ICIs), such as immune checkpoint gene expression and tumor mutation burden (TMB) 12 . Immunotherapy has rapidly become a cornerstone of many cancer therapies, but the response to immunotherapy has not been very promising, with only some patients showing a durable response to immunotherapy 13 .…”

Comprehensive Analysis of DMRT3 as a Potential Biomarker Associated with the Immune Infiltration in a Pan-Cancer Analysis and Validation in Lung Adenocarcinoma

“…The MSI occurs when some cells perform one or two alleles and a varying number of repeats and has been identified to correlate with clinicopathological features of cancer patients [ 31 ]. The TMB is the number of non-synonymous mutations per coding region of the tumor genome, including the somatic variants per megabase (MB) of the genome, identified by the reported algorithm for the whole exome sequencing [ 32 ]. As shown in Figure 4 , the DMRT3 expression was negatively correlated with the MSI status of DLBC ( p = 0.026), ESCA ( p = 0.023), and READ ( p = 0.013).…”

The RELT Family of Proteins: An Increasing Awareness of Their Importance for Cancer, the Immune System, and Development

“…Bioinformatic analysis indicates RELL2 expression is a good prognostic indicator for PDAC. Bioinformatic analysis by a separate group confirmed that higher RELL2 expression was correlated with increased survival and better patient outcomes for pancreatic adenocarcinoma (PAAD) [83]. It is important to note that two separate groups report that post-transcriptional modifications of RELL2 nascent RNA modulate the anti-tumorigenic functions of RELL2 in pancreatic [72] and ESCC [67].…”

“…It is interesting to speculate whether a negative charge introduced by the phosphorylation of RELL1 results in a similar conformation as produced by the N255D mutation, resulting in a pro-tumorigenic form of the protein. In contrast to the upregulation of RELL1 in glioblastoma, bioinformatic analysis indicates that RELL2 is expressed at lower levels in glioblastoma multiforme (GBM) and low-grade gliomas (LGG) versus normal non-malignant tissues [83].…”

“…Curiously, although experimental evidence demonstrates RELL2 possesses antitumorigenic activities in ESCC, PDAC, and breast cancer cell lines, bioinformatic analysis indicates that RELL2 expression is associated with poor outcomes in several cancers [83]. RELL2 was expressed at higher levels in 16 out of the 20 cancers analyzed, with the highest expression levels in rectum adenocarcinoma and HNSC.…”