STAT4, a potential predictor of prognosis, promotes CD8 T‑cell infiltration in ovarian serous carcinoma by inducing CCL5 secretion

Ovarian serous carcinoma (OC) is a common cause of mortality among gynecological malignancies. Although tumor-infiltrating CD8 T cells are associated with a favorable prognosis of OC, the underlying mechanisms are not clearly understood. The present study identified the key genes and potential molecular mechanisms associated with CD8 T-cell infiltration in OC. The score of CD8 T cells in The Cancer Genome Atlas dataset (376 samples from patients with OC) was estimated using the quanTIseq and MCP-counter algorithms. Thereafter, a protein-protein interaction network of differentially expressed genes was constructed and the hub genes were identified using cytoHubba in Cytoscape. The results revealed that signal transducer and activator of transcription 4 (STAT4) was strongly correlated with CD8 T-cell infiltration in OC. Furthermore, the prognostic value of STAT4 in OC was verified by Kaplan-Meier curve, and univariate and multivariate analyses. The biological functions of STAT4 were determined by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, which revealed that STAT4 is closely related to cytokines in OC. Moreover, Spearman correlation analysis suggested that STAT4 was most positively correlated with CC chemokine ligand 5 (CCL5). CCL5 was revealed to be critical for orchestrating T-cell infiltration in tumors. Moreover, immunohistochemistry and reverse transcription-quantitative PCR showed that STAT4, CCL5 and CD8A (a marker for CD8 T cells) were closely related in OC. Moreover, in vitro analysis revealed that STAT4 knockdown led to a decrease in CCL5 expression and CD8 T-cell migration. Taken together, the present study suggested that STAT4 may regulate CD8 T-cell infiltration in OC tissues by inducing CCL5 secretion. Furthermore, STAT4 may be considered a promising prognostic biomarker for OC.