WGCNA identification of TLR7 as a novel diagnostic biomarker, progression and prognostic indicator, and immunotherapeutic target for stomach adenocarcinoma.

Abstract

Stomach adenocarcinoma (STAD) is a malignant tumor with high histological heterogeneity. However, the potential mechanism of STAD tumorigenesis remains to be elucidated. The purpose of our research was to identify candidate genes associated with the diagnosis, progression, prognosis, and immunotherapeutic targets of STAD. Based on tumor samples from the GSE28541 dataset, weighted gene co‐expression network analysis revealed 16 modules related to STAD stage and grade. The salmon module emerged as the most relevant module (cor = 0.34), and functional enrichment analysis showed that the genes in the salmon were primarily related to major histocompatibility complex, immune response, and cell differentiation. Toll‐like receptor 7 (TLR7) was recognized as the real hub gene in the salmon module. Compared to normal stomach tissues, the transcriptional and translational levels of TLR7 were significantly elevated in STAD. Receiver operating characteristic curves verified that TLR7 displayed remarkable sensitivity and specificity for the diagnosis of STAD. The functions of TLR7 were primarily enriched in the regulation of Toll‐like receptor signaling pathway, pattern recognition receptor signaling pathway, and innate immune response. Overexpression of TLR7 tended to indicate more advanced STAD, higher degree of STAD, and poorer prognosis of STAD. In addition, TLR7 expression was positively correlated with immune cell infiltration and immune checkpoint expression. Somatic copy number alteration of TLR7 was also significantly related to immune cell infiltration. In conclusion, this study revealed the crucial role of TLR7 in STAD and provided new perspectives for the selection of biomarkers, progression and prognosis indicators, and immunotherapeutic targets for STAD.