High Expression of Interferon Pathway Genes CXCL10 and STAT2 Is Associated with Activated T-Cell Signature and Better Outcome of Oral Cancer Patients

To improve the survival rate of cancer patients, biomarkers for both early diagnosis and patient stratification for appropriate therapeutics play crucial roles in precision oncology. Investigation of altered gene expression and the relevant molecular pathways in cancer cells are helpful for discovering such biomarkers. In this study, we explore the potential prognostic biomarkers for oral cancer patients through systematically analyzing five oral cancer transcriptomic data sets (TCGA, GSE23558, GSE30784, GSE37991, and GSE138206). Gene Set Enrichment Analysis (GSEA) was individually applied to each data set and the upregulated Hallmark molecular pathways of each data set were intersected to generate 13 common pathways including interferon-α/γ pathways. Among the 5 oral cancer data sets, 43 interferon pathway genes were commonly upregulated and 17 genes exhibited prognostic values in TCGA cohort. After validating in another oral cancer cohort (GSE65858), high expressions of C-X-C motif chemokine ligand 10 (CXCL10) and Signal transducer and activator of transcription 2 (STAT2) were confirmed to be good prognostic biomarkers. GSEA of oral cancers stratified by CXCL10/STAT2 expression showed that activation of T-cell pathways and increased tumor infiltration scores of Type 1 T helper (Th1) and CD8+ T cells were associated with high CXCL10/STAT2 expression. These results suggest that high CXCL10/STAT2 expression can predict a favorable outcome in oral cancer patients.