Clinical significance of long non-coding RNA DUXAP8 and its protein coding genes in hepatocellular carcinoma

Backgrounds: Hepatocellular carcinoma (HCC) is a lethal malignancy worldwide that is difficult to diagnose during the early stages and its tumors are recurrent. Long non-coding RNAs (lncRNAs) have increasingly been associated with tumor biomarkers for diagnosis and prognosis. This study attempts to explore the potential clinical significance of lncRNA DUXAP8 and its co-expression related protein coding genes (PCGs) for HCC. Method: Data from a total of 370 HCC patients from The Cancer Genome Atlas were utilized for the analysis. DUXAP8 and its top 10 PCGs were explored for their diagnostic and prognostic implications for HCC. A risk score model and nomogram were constructed for prognosis prediction using prognosis-related genes and DUXAP8. Molecular mechanisms of DUXAP8 and its PCGs involved in HCC initiation and progression were investigated. Then, potential target drugs were identified using genome-wide DUXAP8-related differentially expressed genes in a Connectivity Map database. Results: The top 10 PCGs were identified as: RNF2, MAGEA1, GABRA3, MKRN3, FAM133A, MAGEA3, CNTNAP4, MAGEA6, MALRD1, and DGKI. Diagnostic analysis indicated that DUXAP8, MEGEA1, MKRN3, and DGKI show diagnostic implications (all area under curves ≥0.7, p≤0.05). Prognostic analysis indicated that DUXAP8 and RNF2 had prognostic implications for HCC (adjusted p=0.014 and 0.008, respectively). The risk score model and nomogram showed an advantage for prognosis prediction. A total of 3 target drugs were determined: cinchonine, bumetanide and amiprilose and they may serve as potential therapeutic targets for HCC. Conclusion: Functioning as an oncogene, DUXAP8 is overexpressed in tumor tissue and may serve as both a diagnostic and prognosis biomarker for HCC. MEGEA1, MKRN3, and DGKI maybe potential diagnostic biomarkers and DGKI may also be potentially prognostic biomarkers for HCC.

DUXAP8; hepatocellular carcinoma; long non-coding RNA; molecular mechanism; protein-coding gene.