Abstract
BACKGROUND: Cervical cancer (CC), which has been increasing in incidence in recent years, is the fourth most common gynecological cancer in the world. Therapy targeting T cell immunoglobulin mucin-3 (Tim-3), known as the immune checkpoint, has been rapidly developing as oncotherapy for various carcinomas. However, few studies focus on Tim-3 in CC in terms of patient prognosis. This study demonstrates that higher Tim-3 mRNA levels in CC are associated with a favorable prognosis, which may due to active immune responses in CC. METHODS: First, the clinical and RNA-sequencing (RNA-seq) data of 287 CC patients were downloaded from The Cancer Genome Atlas (TCGA) database and was subsequently analyzed. Then, based on the Tim-3 mRNA levels, the patients were divided into groups categorized by high and low expression, and the overall survival (OS) among the patients was determined. Next, the correlation between the expression of Tim-3 and clinicopathological variables was investigated. Finally, the Tim-3 function was carried out using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and a gene set enrichment analysis (GSEA) was performed. RESULTS: In CC, the median OS of patients with high Tim-3 expression and low Tim-3 expression were 634 and 491 days (P=0.01), respectively. We found that the high expression of Tim-3 was closely associated with smoking history (P=0.012), total number of pregnancies (P=0.002), histological type (P<0.0001), M stage (P=0.036), TNM stage (P<0.0001), papillomavirus (P=0.001), hysterectomy type (P<0.0001) and survival status (P<0.0001). Univariate and multivariate logistic regression tests suggested that the level of Tim-3 was an independent prognostic factor for CC patients. In addition, GSEA further showed that Tim-3 expression was associated with macrophage differentiation, regulation of monocyte chemotaxis, positive regulation of substrate adhesion dependent cell spreading, negative regulation of interleukin 2 production, regulation of NF kappa-B signaling, STAT cascade, erk1 and erk2 cascade and regulation of vascular endothelial growth factor receptor signaling pathway. CONCLUSIONS: A higher expression of Tim-3 was associated with a favorable prognosis, which may due to the activation of immune responses in tumor tissues.