Abstract
Hepatocellular carcinoma (HCC) is an aggressive cancer type with poor prognosis; thus, there is especially necessary and urgent to screen potential prognostic biomarkers for early diagnosis and novel therapeutic targets. In this study, we downloaded target data sets from the GEO database, and obtained codifferentially expressed genes using the limma R package and identified key genes through the protein–protein interaction network and molecular modules, and performed GO and KEGG pathway analyses for key genes via the clusterProfiler package and further determined their correlations with clinicopathological features using the Oncomine database. Survival analysis was completed in the GEPIA and the Kaplan–Meier plotter database. Finally, correlations between key genes, cell types infiltrated in the tumor microenvironment (TME), and hypoxic signatures were explored based on the TIMER database. From the results, 11 key genes related to the cell cycle were determined, and high levels of these key genes' expression were focused on advanced and higher grade status HCC patients, as well as in samples of TP53 mutation and vascular invasion. Besides, the 11 key genes were significantly associated with poor prognosis of HCC and also were positively related to the infiltration level of MDSCs in the TME and the HIF1A and VEGFA of hypoxic signatures, but a negative correlation was found with endothelial cells (ECs) and hematopoietic stem cells. The result determined that 11 key genes (RRM2, NDC80, ECT2, CCNB1, ASPM, CDK1, PRC1, KIF20A, DTL, TOP2A, and PBK) could play a vital role in the pathogenesis of HCC, drive the communication between tumor cells and the TME, and act as probably promising diagnostic, therapeutic, and prognostic biomarkers in HCC patients.
Highlights
Hepatocellular carcinoma (HCC), an aggressive cancer type with poor prognosis, ranks fifth in cancer incidence worldwide and is the second most frequent cause of cancerrelated mortality [1, 2]
We found that the high expression of NDC80, CCNB1, CDK1, PRC1, KIF20A, DTL, and TOP2A was significantly associated with worse overall survival (OS) in advanced T-stage (T2–3) patients (Figure 10)
Our findings demonstrated that the key genes might promote liver cirrhosis and HCC progression and tended to indicate a poor prognosis, which might be largely due to the consequence of the key genes driving the communications between tumor cells and the tumor microenvironment (TME) and accelerating the formation of a hypoxic and immunosuppressive microenvironment
Summary
Hepatocellular carcinoma (HCC), an aggressive cancer type with poor prognosis, ranks fifth in cancer incidence worldwide and is the second most frequent cause of cancerrelated mortality [1, 2]. Long-term injury, and regeneration processes perpetuate liver fibrosis and result in distortion of lobular architecture, nodular formation, and cirrhosis; the dysplastic cirrhotic nodules continue to evolve and eventually develop into early-stage and advanced HCC [4, 5]. To reduce the risk of hepatocarcinogenesis, adequate monitoring of symptoms, follow-up and BioMed Research International evaluation of disease status, and improved early diagnosis and targeted therapies are important for patients with chronic liver disease who are at high risk of HCC. While surgical resections can cure patients at early-stage of HCC [8], the reality is, that most patients are not suitable for potentially curative therapy due to the high burden of liver disease, extra-hepatic spread, poor background liver function related to cirrhosis, or the advanced stage at the time of diagnosis [9, 10]. The identification of novel and effective markers for early warning for HCC and the exploration of new therapeutic targets for liver diseases are urgently needed
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