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.
Highlights
T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT), an immune checkpoint, plays a pivotal role in immune suppression
The TIGIT expression was downregulated in Thyroid carcinoma (THCA) based on The Cancer Genome Atlas (TCGA) datasets
The results showed the prognostic impact of TIGIT across the different cancer types
Summary
T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT), an immune checkpoint, plays a pivotal role in immune suppression. 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. Under chronic exposure to tumor antigens, T cells become dysfunctional/exhausted and upregulate several IRs including programmed cell death receptor 1 (PD-1) and TIGIT12,13 Immunotherapies such as Immune checkpoint blockades (ICBs) have achieved great progress and show tremendous potentiality, especially for those patients with resistance to c hemoradiotherapy[14,15]. In this research, taking advantages of TCGA and GTEx datasets, we conducted a comprehensive analysis at pan-cancer level to illustrate the TIGIT expression profiles, prognostic values and its correlation with immune
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