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• An OA predictive model based on 4 m7G hub genes (SNUPN, METTL1, EIF4E2 and CYFIP1) was constructed. • Two m7G methylation patterns in OA were found to show distinct biological characteristics, and an m7G score were generated. • M7G cluster A and a higher m7G score were found to be related to an inflamed phenotype. Accumulating evidence has shown that aberrant N7-methylguanosine (m7G) RNA methylation played an important role in the occurrence and development of cancer. However, knowledge of m7G modifications in inflammatory diseases is limited. Osteoarthritis (OA) is the most common arthritic disease with poor prognosis. Our research aimed to identify m7G-related hub biomarkers and investigate m7G regulator expression pattern in immune landscape of OA patients. Gene expression profiles and their clinical information were obtained from the Gene Expression Omnibus (GEO) database, and differential analysis of 14 m7G-related regulators between elective OA and normal samples was performed. M7G-related hub genes for OA were mined based on single-sample gene set enrichment analysis (ssGSEA) and the random forest (RF) algorithm, and qRT-PCR was performed to confirm the abnormal expression of hub genes. Enrichment, protein–protein interaction (PPI), transcription factor (TF)-gene interaction and microRNA (miRNA)-gene coregulatory analysis based on m7G hub genes were performed. Then we predicted several candidate drugs related to m7G hub genes using DSigDB database. Moreover, we comprehensively evaluated m7G methylation patterns in OA samples and systematically correlated these modification patterns with the characteristics of immune cell infiltration. The m7G score was generated to quantify m7G methylation patterns for individual OA patients by the application of principal component analysis (PCA) algorithm. We constructed an OA predictive model based on 4 m7G hub genes (SNUPN, METTL1, EIF4E2 and CYFIP1). Two m7G methylation patterns in OA were discovered to show distinct biological characteristics, and an m7G score were generated. M7G cluster A and a higher m7G score were found to be related to an inflamed phenotype. Our study was the first to comprehensively investigate the m7G methylation dysregulations in immune landscape during the progression of OA. These 4 m7G gene-related signatures can be used as novel OA biomarkers to predict the occurrence of OA. Evaluating the m7G methylation patterns of OA individuals will contribute to enhancing our cognition of immune infiltration characterization and guiding more effective immunotherapy strategies. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) development and progression is significantly associated with tumour immune escape. T cell immunoreceptor with Ig and ITIM domains (TIGIT) inhibits T-cell responses and is associated with human cancers and T cell exhaustion phenotypes, but its role in cancers remains unclear. TIGIT and programmed cell death protein (PD)-1 levels were detected in 441 human GC specimens using histochemistry. We used flow cytometry to evaluate percentage of TIGIT+ constituting CD8+ T cells of 23 patients with GC who underwent D2 gastrectomy and the S-1 plus oxaliplatin (SOX) regimen. We investigated the influence of SOX regimen and TIGIT functional antibody on CD8 tumour-infiltrating lymphocytes (TILs). Results showed that PD-1 and TIGIT were significantly over expressed in GC and predicted poorer outcome, agreeing with bioinformatics analysis. Significantly reduced percentages of CD8+ TIGIT+ cells were observed in patients after D2 gastrectomy (pre- vs post-surgery, 38 ± 8.7% vs. 26.7% ± 5.2%, p < 0.0001). TIGIT expression on CD8+T cells was modulated by chemotherapeutics (pre- and post-chemotherapy, 31.3 ± 9% vs. 25.1 ± 4.5%, respectively, p = 0.0047) and higher TIGIT expression in post-chemotherapy group was associated with relapsed GC (p = 0.036). In vitro experiments revealed increased CD8+ TIL proliferation and interferon (IFN)-γ production following SOX regimen and TIGIT functional antibody treatments. In conclusion, TIGIT contributes to CD8+ TILs immune dysfunction in patients with GC. Combination of anti-TIGIT therapy and chemotherapy could be considered a therapy for GC. [ABSTRACT FROM AUTHOR]