Stress granule regulator-associated genes predict drug sensitivity, immune infiltration, and prognosis in patients with gastric cancer: Insights from bioinformatic and experimental approaches.

[OBJECTIVE] Stress granule (SG) regulators affect tumor progression in patients with gastric cancer (GC). This study aimed to explore the effects of SG-related genes on the prognosis, immune characteristics, and drug sensitivity of patients with GC.

[METHODS] Key SG-related genes in GC were identified from public databases. Univariate and multivariate Cox regression analyses were adopted to highlight prognostic genes and construct a prognostic model, whose efficacy was assessed using Kaplan-Meier and receiver operating characteristic curves. SG-related subtypes in GC were identified through consensus clustering. Differences in the distribution of risk-stratified samples, molecular functions, expression profiles, drug sensitivity, and immune infiltration levels were compared. Prognostic gene expression was validated using real-time quantitative polymerase chain reaction and western blotting. In sh-CRYAB-transfected cells, the effects of CRYAB on cell viability, invasion, and colocalization with the GC scaffold protein G3BP1 were assessed using a cell counting kit-8 assay, a Transwell assay, and immunofluorescence, respectively.

[RESULTS] Among 86 SG-related genes identified in GC, four prognostic genes (FHL1, TMPO, SERPINE1, and CRYAB) were recognized as potential diagnostic markers. These genes enabled the construction of a prognostic model capable of predicting clinical outcomes in GC. Two distinct SG-related molecular subtypes were also identified, with subtype 1 associated with a more favorable prognosis. These subtypes differed significantly in the expression patterns and biological functions of prognostic genes. Furthermore, the four prognostic genes were significantly associated with drug sensitivity and immune cell infiltration. These genes were overexpressed at both the mRNA and protein levels, except FHL1, which was downregulated in GC cells. CRYAB deficiency significantly inhibited cell proliferation, invasion, and cytoplasmic colocalization with G3BP1 in GC cells.

[CONCLUSION] FHL1, TMPO, SERPINE1, and CRYAB are potential prognostic markers in GC. CRYAB may facilitate GC progression by regulating G3BP1-mediated SG assembly.