A Novel Gene Pair CSTF2/DPE2A Impacts Prognosis and Cell Cycle of Hepatocellular Carcinoma

Abstract

Background

Hepatocellular carcinoma (HCC), one of the commonest cancers at present, possesses elevated mortality. This study explored the predictive value of CSTF2/PDE2A for HCC prognosis.

Methods

In this study, clinical information and RNA sequencing expression profiles of HCC patients were acquired from common databases. Kaplan–Meier curve compound with time-dependent ROC curve, nomogram model, and univariate/multivariate Cox analysis were carried out to access the prediction capacity of CSTF2/PDE2A. The immune status, tumor microenvironment, drug sensitivity, biological function and pathway between HCC and adjacent non-tumorous tissue were analyzed and compared. Finally, RT-qPCR, Western blot, and apoptosis assays were performed to verify the effect on HCC cells of CSTF2/PDE2A.

Results

The optimal cut-off value of CSTF2, PDE2A and CSTF2/PDE2A was 6.95, 0.95 and 3.63, respectively. In TCGA and ICGC cohorts, the high group of CSTF2/PDE2A presented higher OS compared to low group. The area under the curve (AUC) for OS at 1-, 2-, and 3-years predicted by CSTF2/PDE2A were 0.731/0.695, 0.713/0.732 and 0.689/0.755, higher than the counterparts of the single gene CSTF2 and PDE2A. Multivariate Cox analysis revealed that CSTF2/PDE2A (HR = 1.860/3.236, 95% CI = 1.265–2.733/1.575–6.645) was an independent prognostic factor for HCC. The OS nomogram model created according to five independent factors including CSTF2/PDE2A showed excellent capacity for HCC prognosis. Furthermore, the immune status of the CSTF2/PDE2A high group was deleted, cell cycle-related genes and chemotherapy resistance were increased. Finally, cell experiments revealed distinct differences in the proliferation, apoptosis, protein and mRNA expression of HCC cells after si-CSTF2 transfection compared with the negative control.

Conclusion

Taken together, the gene pair CSTF2/PDE2A is able to forecast the prognosis of HCC and regulates cell cycle, which is promising as a novel prognostic predictor of HCC.