Construction and validation of a signature for T cell-positive regulators related to tumor microenvironment and heterogeneity of gastric cancer

Abstract

BackgroundPositive regulators of T cell function play a vital role in the proliferation and differentiation of T cells. However, their functions in gastric cancer have not been explored so far.MethodsThe TCGA-STAD dataset was utilized to perform consensus clustering in order to identify subtypes related to T cell-positive regulators. The prognostic differentially expressed genes of these subtypes were identified using the least absolute shrinkage and selection operator (LASSO) regression analysis. To validate the robustness of the identified signature, verification analyses were conducted across the TCGA-train, TCGA-test, and GEO datasets. Additionally, a nomogram was constructed to enhance the clinical efficacy of this predictive tool. Transwell migration, colony formation, and T cell co-culture assays were used to confirm the function of the signature gene in gastric cancer and its influence on T cell activation.ResultsTwo distinct clusters of gastric cancer, related to T cell-positive regulation, were discovered through the analysis of gene expression. These clusters exhibited notable disparities in terms of survival rates (P = 0.028), immune cell infiltration (P< 0.05), and response to immunotherapy (P< 0.05). Furthermore, a 14-gene signature was developed to classify gastric cancer into low- and high-risk groups, revealing significant differences in survival rates, tumor microenvironment, tumor mutation burden, and drug sensitivity (P< 0.05). Lastly, a comprehensive nomogram model was constructed, incorporating risk factors and various clinical characteristics, to provide an optimal predictive tool. Additionally, an assessment was conducted on the purported molecular functionalities of low- and high-risk gastric cancers. Suppression of DNAAF3 has been observed to diminish the migratory and proliferative capabilities of gastric cancer, as well as attenuate the activation of T cells induced by gastric cancer within the tumor microenvironment.ConclusionWe identified an ideal prognostic signature based on the positive regulators of T cell function in this study.

Predictive Factors of Immunotherapy in Gastric Cancer: A 2024 Update

“…Gene expression analysis revealed two unique GC clusters associated with positive T-cell regulation. It has been demonstrated that suppressing Dynein Axonemal Assembly Factor 3 (DNAAF3) reduces GCs’ capacity for migration and proliferation as well as their ability to activate T lymphocytes inside the TME [ 26 ].…”

“…age and the GARGs were found to be separate risk factors for GC [23] the E2F score is a useful predictor of survival and responsiveness to treatment [24] the low-risk group of GC patients (with genes involved in the DNA repair pathway) are likely to benefit more from immunotherapy [25] suppressing DNAAF3 reduces GCs' capacity for migration and proliferation as well as their ability to activate T lymphocytes inside the TME [26] Table 2. Cont.…”

Oncolytic Virus Senecavirus A Inhibits Hepatocellular Carcinoma Proliferation and Growth by Inducing Cell Cycle Arrest and Apoptosis

“…The cells were then fixed with 4% paraformaldehyde (Solarbio, China) for 30 m, stained with 0.1% crystal violet (Solarbio, China) for 15 m at room temperature, and imaged. 22 Colonies were quantified using ImageJ software.…”