Abstract
Since angiogenesis has an indispensable effect in the development and progression of tumors, in this study we aimed to identify angiogenic genes closely associated with prognosis of HCC to establish diagnostic, prognostic, and recurrence models. We analyzed 132 angiogenic genes and HCC-related RNA sequence data from the TCGA and ICGC databases by Cox and least absolute shrinkage and selection operator (LASSO) regression, and identified four angiogenic genes (ENFA3, EGF, MMP3 and AURKB) to establish prognosis, recurrence and diagnostic models and corresponding nomograms. The prognostic and recurrence models were determined to be independent predictors of prognosis and recurrence (P < 0.05). And compared with the low-risk group, patients in the high-risk group had worse overall survival (OS) rates in training cohort (P < 0.001) and validation cohort (P < 0.001), and higher recurrence rates in training cohort (P<0.001) and validation cohort (P=0.01). The diagnostic models have been validated to correctly distinguish HCC from normal samples and proliferative nodule samples. Through pharmacological analysis we identified piperlongumine as a drug for targeting angiogenesis, and it was validated to inhibit HCC cell proliferation and angiogenesis via the EGF/EGFR axis.
Highlights
Liver cancer is estimated to be the sixth most common cancer in the world (841,000 cases/year) and the fourth leading cause of cancer (782,000 cases/year), and it poses a serious health threat and economic burden to the world [1]
We identified 132 angiogenic genes from several studies on angiogenesis, and we matched these genes to HCCrelated mRNA sequence data in TCGA and ICGC databases; we compared differentially expressed genes (DEGs) in the mRNA expression profiles between Hepatocellular carcinoma (HCC) tissues and adjacent noncancerous tissues
To identify angiogenic genes that were significantly associated with HCC survival, we performed least absolute shrinkage and selection operator (LASSO) regression and Cox regression analysis
Summary
Liver cancer is estimated to be the sixth most common cancer in the world (841,000 cases/year) and the fourth leading cause of cancer (782,000 cases/year), and it poses a serious health threat and economic burden to the world [1]. 85%) of primary liver cancer, and its increasing worldwide incidence and mortality has generated major clinical interest. There are various treatment strategies for different characteristics of HCC. Transplantation, ablation, and trans-arterial chemoembolization have been shown to produce survival benefits [2, 3], but due to the high recurrence rate after surgery, the prognosis of HCC patients is still www.aging-us.com unsatisfactory, and OS and RFS are still very poor [4, 5]. Accurate prognosis assessment is a key step in the effective management and treatment of patients with HCC. To develop more effective treatment management strategies for improving the survival status and clinical outcomes of HCC patients, it is urgent that new, efficient molecular prognostic markers be explored
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