A pan-cancer analysis revealing the role of TIGIT in tumor microenvironment

Abstract

T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT), an immune checkpoint, plays a pivotal role in immune suppression. However its role in tumor immunity and correlation with the genetic and epigenetic alterations remains unknown. Here, we comprehensively analyzed the expression patterns of the TIGIT and its value of prognostic prediction among 33 types of cancers based on the data collected from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression projects (GTEx). Furthermore, the correlations of TIGIT with pathological stages, tumor-infiltrating immune cells (TIICs), signatures of T cells subtypes, immune checkpoint genes, the degree of Estimation of STromal and Immune cells in MAlignant Tumor tissues using the Expression data (ESTIMATE), tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR) genes, and DNA methyltransferases (DNMTs) were also explored. Gene functional enrichment was conducted by Gene Set Enrichment Analysis (GSEA). Our results showed that the expression of TIGIT was upregulated in most of the cancer types. Cox regression model showed that high expression of TIGIT in tumor samples correlates with poor prognosis in KIRC, KIRP, LGG, UVM, and with favorable prognosis in BRCA, CECS, HNSC, SKCM. TIGIT expression positively correlated with advanced stages, TIICs, the signatures of effector T cells, exhausted T cells, effector Tregs and the degree of ESTIMATE in KIRC, KIRP and UVM. TIGIT expression also positively correlated with CTLA4, PDCD1 (PD-1), CD274 (PD-L1), ICOS in most of the cancer types. Furthermore, the expression of TIGIT was correlated with TMB, MSI, MMR genes and DNMTs in different types of cancers. GSEA analysis showed that the expression of TIGIT was related to cytokine-cytokine receptor interaction, allograft rejection, oxidative phosphorylation. These findings suggested that TIGIT could serve as a potential biomarker for prognosis and a novel target for immunotherapies in cancers.

Update in TIGIT Immune-Checkpoint Role in Cancer

“…TIGIT overexpression has been found in the cellular microenvironment of several tumors, including lung ( 111 ), kidney ( 112 ), liver ( 113 ), glioma ( 114 , 115 ), melanoma ( 116 ), colorectal carcinomas ( 117 ), gastric cancer ( 118 ), and neuroblastomas ( 119 ). TIGIT expression was found to be strongly associated with poor prognosis in colorectal cancer and positively correlated with pathological stages in renal clear cell carcinoma ( 120 ), kidney renal papillary cell carcinoma, and uveal melanoma ( 121 , 122 ).…”

Comprehensive analysis of epigenetics regulation, prognostic and the correlation with immune infiltrates of GPX7 in adult gliomas

“…Several studies have highlighted the suppressive impact of TIGIT on a wide range of immune functions and immune cells (e.g., T/NK cells) 163 – 165 . Besides, TIGIT + Treg cells selectively inhibit pro-inflammatory Th1 and Th17 cell responses, but not Th2 cell responses 166 .…”

Based on Molecular Subtypes, Immune Characteristics and Genomic Variation to Constructing and Verifying Multi-Gene Prognostic Characteristics of Colorectal Cancer

“…We extracted the DEGs of these two groups of COAD to screen the genes that perform an instrumental function in tumors. The results of pathway enrichment suggest that the pathways involved by these genes are concentrated in Cell adhesion molecules (CAMs) ( Bronikowska et al, 2021 ), cytokine receptor interaction ( Wen et al, 2021 ), focal adhesion ( Lu et al, 2021 ), NF kappa B signaling pathway ( Takakura et al, 2021 ), proteoglycans in cancer ( Jinmin Sun et al, 2021 ), PI3K Akt signaling pathway ( Xue et al, 2021 ), etc, which are strongly associated with to the onset and progression of tumors. Further cluster analysis showed that CryptLike, EMT, Collective and Proliferative were distributed in different modules respectively.…”