Prognostic Role of TIGIT Expression in Patients with Solid Tumors: A Meta-Analysis

Abstract

Background. T cell immunoglobulin and ITIM domain (TIGIT) is a recently identified immunosuppressive receptor. The expression levels of TIGIT affect the prognosis of patients with solid tumors. To fully comprehend the role of TIGIT on the prognosis of patients with solid tumors, we conducted a meta-analysis. Methods. We performed an online search of PubMed, Embase, Web of Science (WOS), and MEDLINE databases for literature published till March 31, 2021. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the literature, and Stata 16.0 and Engauge Digitizer 4.1 software were used for data analysis. Results. Our literature search identified eight papers comprising 1426 patients with solid tumors. Increased expression of TIGIT was associated with poor prognosis. High expression of TIGIT was a risk factor for overall survival (OS) { hazard ratio HR = 1.66 , 95% confidence interval (CI) [1.26, 2.20], P < 0.001 } and progression-free survival (PFS) ( HR = 1.44 , 95% CI [1.15, 1.81], P = 0.01 ). We performed subgroup analysis to explore the source of heterogeneity, colorectal cancer ( HR = 2.07 , 95% CI [0.23, 18.82], P = 0.518 ), lung cancer ( HR = 1.29 , 95% CI [0.96, 1.72], P = 0.094 ), esophageal cancer ( HR = 1.70 , 95% CI [1.20, 2.40], P = 0.003 ), and other cancers ( HR = 1.83 , 95% CI [1.25, 2.68], P = 0.002 ). In addition to cancer type, expression location, sample size, and different statistical analysis methods are also considered the possible causes of heterogeneity between studies. Funnel plots suggested no publication bias for OS ( P = 0.902 ), and Egger’s test supported this conclusion ( P = 0.537 ). Conclusion. TIGIT expression was associated with OS and PFS in patients with solid tumors. Patients with elevated TIGIT expression have a shorter OS and PFS, and TIGIT expression could be a novel biomarker for prognosis prediction and a valuable therapeutic target for solid tumors.

Prognostic value of TIGIT in East Asian patients with solid cancers: A systematic review, meta-analysis and pancancer analysis

“…The results of the meta-analysis showed that high expression of TIGIT was associated with poorer OS, PFS, RFS and DFS in East Asian patients with solid cancers. In contrast to the study reported by Kunmin Xiao et al ( 42 ), we also discussed the relationship between TIGIT and DFS and RFS. DFS and RFS are important clinical outcomes for cancers with relatively good clinical prognosis.…”

TIGIT Expression on Intratumoral Lymphocytes Correlates with Improved Prognosis in Oral Squamous Cell Carcinoma

“…Extensive analysis of gene databases also revealed a beneficial role of TIGIT in head and neck or breast cancer, while in renal clear cell carcinoma, tumors expressing TIGIT demonstrated poorer patient outcomes [ 38 ]. On the other hand, a meta-analysis from 2021 found TIGIT expression in different solid tumors to be negatively associated with survival [ 39 ]. These findings demonstrate the controversial role of TIGIT in the clinical setting, which makes it difficult to define TIGIT as a predictive biomarker in clinical practice.…”

What Inhibits Natural Killers’ Performance in Tumour

“…T cell immunoglobulin and ITIM domain (TIGIT), also known as WUCAM, Vstm3, and VSIG9, is a recently discovered co-inhibitory receptor classified as a member of the poliovirus receptor (PVR)/nectin family. TIGIT is primarily expressed in T cells and NK cells [56]. In addition, it has been suggested as a marker of natural thymus-derived regulatory T cells (tTregs) with strong suppressive activity and lineage stability [57].…”

“…TIGIT knockout leads to hyperproliferative T cell responses, increases levels of proinflammatory cytokines, and hinders IL-10 production [58]. TIGIT expression on tumour infiltrating lymphocytes (TILs) was reported in a variety of malignancies [56,59] and negatively correlated with patient survival [56]. PVR known as CD155 (Necl5 or Tage4) was identified as a high-affinity receptor for TIGIT, while PVRL3 and CD112 (also known as PVRL2/nectin 2) bound TIGIT with lower affinity [60].…”