Suppressor of TCR signaling 2 (Sts-2) as a potential immunotherapy target and prognostic biomarker in cervical cancer.

Abstract

Objective: More efficient immune targets are needed for the treatment of cervical cancer. This study aimed to identify potential targets for immunotherapy and prediction in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) by conducting bioinformatics analysis and verifying the results with clinical tissue samples.

Methods: A retrospective analysis of RNA sequencing data from 304 patients sourced from The Cancer Genome Atlas (TCGA) and another 300 patients from the Gene Expression Omnibus (GEO) was performed to investigate the correlation between suppressor of TCR signaling 2 (Sts-2) expression and clinical parameters in cervical cancer. To authenticate our findings, we utilized a combination of immunohistochemistry, quantitative polymerase chain reaction, and western blotting techniques in a separate cohort consisting of 6 cervical cancer tissue samples.

Results: The Sts-2 gene was discovered to be substantially co-expressed with a multitude of immune checkpoint molecules, including programmed cell death protein 1 (r=0.8, p<0.001), TIGIT (r=0.87, p<0.001), LAG3 (r=0.71, p<0.001), and CTLA4 (r=0.74, p<0.001), in CESC patients. Both the TCGA and GEO datasets have independently validated that Sts-2 expression levels significantly correlate with overall survival rates, thus demonstrating its prognostic importance. A single-gene Gene Set Enrichment Analysis indicated that Sts-2 was highly enriched in T cell-related immune pathways. Moreover, using the Tumor Immune Dysfunction and Exclusion algorithm, it was suggested that high Sts-2 expression might predict a more favorable response to immunotherapy.

Conclusion: The heightened expression of Sts-2 serves as a dual indicator of elevated T cell content and a favorable prognosis in cervical cancer.