Pan-Cancer Analysis Reveals Ribonuclease K (RNASEK) as a Potential Prognostic Biomarker in Pancreatic Cancer and a Diagnostic Indicator Across Multiple Human Cancers.

Background: Cancer is marked by rapid abnormal cell growth, leading to high mortality. The human Ribonuclease K (RNASEK) gene is involved in various cellular processes, such as viral infection, immune response, and maintaining cellular homeostasis. RNASEK, found in metazoans, contributes to tumor development, but the lack of systemic pan-cancer investigation into the diagnostic and prognostic function of RNASEK, epigenetic regulation, and interaction with the immune cell infiltration remains unclear. This study investigated RNASEK as a potential pan-cancer biomarker.

Methodology: Public databases such as Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), and University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) assessed RNASEK expression patterns. Gene Expression Omnibus (GEO) datasets validated these expressions. UALCAN examined RNASEK's expression differences, DNA methylation, and clinical features. TIMER analyzed SNHG8 expression about immune cell infiltration, while prognosis was evaluated through GEPIA, UALCAN, and Kaplan-Meier (KM) Plotter. cBioPortal reviewed the genetic alterations of RNASEK.

Results: Our study revealed a significant upregulation of RNASEK (< 0.05) in six cancers: bladder (BLCA), cholangiocarcinoma (CHOL), esophageal (ESCA), head/neck squamous cell (HNSC), liver (LIHC), and thyroid (THCA). This was accompanied by notable hypomethylation in BLCA, HNSC, LIHC, and Uterine Corpus Endometrial Carcinoma (UCEC), associated with increased RNASEK expression. Significant differences (< 0.05) were noted between stage 1 and stage 3 in ESCA, HNSC, and THCAas well as significant differences (< 0.05) in HNSC between African-American and Asian populations. Additionally, age-related expression differences were significant (< 0.05) in HNSC across young (21-40 years), middle-aged (41-60 years), and older (61-80 years) groups. A weak positive correlation (< 0.05) existed between RNASEK expression and various immune cell infiltrations such as B cells, CD8+ T-cells, CD4+ T-cells, macrophages, neutrophils, and dendritic cells in patients with BLCA, ESCA, HNSC, and LIHC, while THCA presented moderate negative correlations with CD4+ T-cells and neutrophils. Moreover, High RNASEK expression indicated a good prognosis in pancreatic adenocarcinoma (PAAD) (hazard ratio (HR) 0.49, = 0.0007). RNASEK was altered in less than 1% (95 samples out of 10,967 samples) across various tumor types. The highest alteration rates were identified as significant deletions in miscellaneous neuroepithelial tumors, one case out of 31 cases (3.23%), amplifications in sarcoma, four cases out of 255 cases (1.96%), and mutations in endometrial cancer, which is two cases out of 586 (0.34%).

Conclusions:  In conclusion, this study's pan-cancer analysis revealed that RNASEK could be a potential diagnostic biomarker in six cancer types, including BLCA, CHOL, ESCA, HNSC, LIHC, and THCA, and as a prognostic biomarker in PAAD.