Identification and Validation of Hub Genes with Poor Prognosis in Hepatocellular Carcinoma by Integrated Bioinformatical Analysis

Abstract

Background: Hepatocellular carcinoma (HCC) is the reason for the world's second largest cancer-related death. It is clinically valuable to study the molecular mechanisms of HCC occurrence and development for formulating more effective diagnosis and treatment strategies. Methods: The five microarray data sets GSE45267, GSE101685, GSE84402, GSE62232 and GSE45267 were downloaded from Gene Expression Omnibus (GEO) database, including 165 HCC tissues and 73 normal tissues. Differential expressed genes (DEGs) between HCC tissues and normal tissues were determined by GEO2R. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and the protein-protein interaction network (PPI) network analysis were employed to identify DEGs and to evaluate the clinical significance in prognosis of HCC. Results: A total of 152 genes differentially expressed in HCC tissues and normal tissues were identified. GO and KEGG functional enrichment analysis revealed that 39 up-regulated genes were mainly enriched in mitosis, cell cycle and oocyte meiosis, while those down-regulated genes (113) were concentrated in exogenous drug catabolism and the metabolism of cytochrome P450 on exogenous drugs. Totally, 19 hub genes were chosen by PPI network and module analysis and verified by The Cancer Genome Atlas (TCGA) database. Finally, 8 hub genes were selected, including CDK1, CYP2C8, CCNB1, AURKA, CYP2C9, BUB1B, MAD2L1 and TTK, which were associated with the overall survival rate of HCC patients. Conclusion: This study presented eight target genes connected to the prognosis of HCC patients. Those mainly exists in cell cycle and drug catabolism, which may be latent targets for clinical treatment.

Comprehensive pan-cancer analysis and the regulatory mechanism of AURKA, a gene associated with prognosis of ferroptosis of adrenal cortical carcinoma in the tumor micro-environment

“…Related studies have also shown high levels of AURKA as an indicator of poor prognosis in bladder cancer. It is also associated with the development and prognosis of rectal cancer, hepatocellular carcinoma, and head and neck cancer ( Lu et al, 2021 ; Tsepenko et al, 2021 ; Guo et al, 2022 ; Huang et al, 2022 ). This research discovered that high AURKA was related to a bad prognosis in various malignancies by creating a deep forest graph and feeding back the association between AURKA, overall survival, and disease-specific survival.…”

The role of Aurora kinase A in hepatocellular carcinoma: Unveiling the intriguing functions of a key but still underexplored factor in liver cancer

“…Numerous studies have investigated AURKA expression across publicly available gene expression datasets, all highlighting the higher expression of AURKA in tumours compared to non-cancerous tissues (Table 1). [66][67][68][69][70][71][72][73][74][75][76][77][78] AURKA showed a marked increase in Hepatitis B virus + (HBV + ) HCC samples compared to the paired HBV + non-tumoural liver tissues in GSE14520 [128.00 (78.79-219.79) 68 By using integrated bioinformatics analyses, most of these studies have identified AURKA as one of the central hub genes with crucial functions in HCC. [68][69][70][71][72][73][75][76][77] Other studies have independently supported this evidence, such as the research conducted by Jeng and colleagues.…”

“…[66][67][68][69][70][71][72][73][74][75][76][77][78] AURKA showed a marked increase in Hepatitis B virus + (HBV + ) HCC samples compared to the paired HBV + non-tumoural liver tissues in GSE14520 [128.00 (78.79-219.79) 68 By using integrated bioinformatics analyses, most of these studies have identified AURKA as one of the central hub genes with crucial functions in HCC. [68][69][70][71][72][73][75][76][77] Other studies have independently supported this evidence, such as the research conducted by Jeng and colleagues. They observed AURKA overexpression in tumours compared to the distal portion of the liver collected from 137 HCC patients at the local hospital (Table 2).…”

“…The role of AURKA as a prognostic biomarker in HCC Jeng and colleagues observed that AURKA overexpression in HCC patients was associated with high-grade disease (grades II-IV) and portal vein tumour invasion (stages IIIB-IV),79 representing one of the first studies to suggest a possible role for AURKA as a prognostic biomarker for HCC patients. By querying the TCGA database, other studies showed that patients with higher AURKA expression had shorter OS [Hazard ratio (HR) = 1.9, p < 0.001]66,67,78,146,147 and DFS (HR = 1.6, p = 0.001)66,70,78,147 compared to low-AURKA group (n = 181 vs. n = 181) using the median AURKA expression as the cutoff value (Table3). A slight improvement in HR was obtained when the best-performing cut-off value was selected to divide the population into two groups.…”

Construction and validation of a prognosis signature based on the immune microenvironment in gastric cancer

“…nlm.nih.gov/geo/ and https://portal.gdc.cancer.gov/. The "limma" package was applied to perform deduplication and log2(x + 1) normalization processing on gene expression data (8).…”