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Investigation of the clinical significance and prospective molecular mechanisms of cystatin genes in patients with hepatitis B virus?related hepatocellular carcinoma.

ABSTRACT: The present study aimed to investigate the clinical significance and prospective molecular mechanism of cystatin (CST) genes in patients with hepatitis B virus (HBV)?related hepatocellular carcinoma (HCC). The role of CST genes in the molecular mechanism of HCC was revealed through bioinformatics analysis. The clinical significance of CST genes was investigated using GSE14520?derived data from patients with HBV?related HCC. Gene set enrichment analysis (GSEA) was used to identify pathways in which the CST genes were enriched, as well as the association between these pathways and HCC. The expression levels of CST1, CST2, CST5, CSTA and CSTB genes were higher in HCC tissue compared with in normal tissue; conversely, CST3 and CST7 were reduced in HCC tissue. Subsequent receiver operating characteristic analysis of the CST genes demonstrated that CST7 and CSTB genes may function as potential diagnostic markers for HCC. Furthermore, the expression levels of CST6 and CST7 were strongly associated with recurrence?free survival and overall survival of patients with HBV?related HCC. GSEA of the CST genes revealed that CST7 was significantly enriched in tumor evasion and tolerogenicity, cancer progenitors, liver cancer late recurrence, liver cancer progression and several liver cancer subclasses. In addition, CST genes demonstrated homology in terms of protein structure and were revealed to be strongly co?expressed. The present findings suggested that CST7 and CSTB genes may serve as potential prognostic and diagnostic biomarkers for HCC.

SUBMITTER: Zhou X

PROVIDER: S-EPMC6549101 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Investigation of the clinical significance and prospective molecular mechanisms of cystatin genes in patients with hepatitis B virus‑related hepatocellular carcinoma.

Zhou Xin X Wang Xiangkun X Huang Ketuan K Liao Xiwen X Yang Chengkun C Yu Tingdong T Liu Junqi J Han Chuangye C Zhu Guangzhi G Su Hao H Qin Wei W Han Quanfa Q Liu Zhengqian Z Huang Jianlv J Gong Yizhen Y Ye Xinping X Peng Tao T

Oncology reports 20190509 1

The present study aimed to investigate the clinical significance and prospective molecular mechanism of cystatin (CST) genes in patients with hepatitis B virus (HBV)‑related hepatocellular carcinoma (HCC). The role of CST genes in the molecular mechanism of HCC was revealed through bioinformatics analysis. The clinical significance of CST genes was investigated using GSE14520‑derived data from patients with HBV‑related HCC. Gene set enrichment analysis (GSEA) was used to identify pathways in whi ...[more]

PMID: 31115549

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Project description:There is limited data on the molecular mechanisms whereby hepatitis D virus (HDV) promotes liver cancer. Therefore, serum and liver specimens obtained at the time of liver transplantation from well-characterized patients with HDV-HCC (n = 5) and with non-HCC HDV cirrhosis (n = 7) were studied using an integrated genomic approach. Transcriptomic profiling was performed using laser capture-microdissected (LCM) malignant and nonmalignant hepatocytes, tumorous and nontumorous liver tissue from patients with HDV-HCC, and liver tissue from patients with non-HCC HDV cirrhosis. HDV-HCC was also compared with hepatitis B virus (HBV) HBV-HCC alone, and hepatitis C virus (HCV) HCV-HCC. HDV malignant hepatocytes were characterized by an enrichment of upregulated transcripts associated with pathways involved in cell-cycle/DNA replication, damage, and repair (Sonic Hedgehog, GADD45, DNA-damage-induced 14-3-3σ, cyclins and cell-cycle regulation, cell cycle: G2-M DNA-damage checkpoint regulation, and hereditary breast cancer). Moreover, a large network of genes identified functionally relate to DNA repair, cell cycle, mitotic apparatus, and cell division, including 4 cancer testis antigen genes, attesting to the critical role of genetic instability in this tumor. Besides being overexpressed, these genes were also strongly coregulated. Gene coregulation was high not only when compared with nonmalignant hepatocytes, but also to malignant hepatocytes from HBV-HCC alone or HCV-HCC. Activation and coregulation of genes critically associated with DNA replication, damage, and repair point to genetic instability as an important mechanism of HDV hepatocarcinogenesis. This specific HDV-HCC trait emerged also from the comparison of the molecular pathways identified for each hepatitis virus-associated HCC. Despite the dependence of HDV on HBV, these findings suggest that HDV and HBV promote carcinogenesis by distinct molecular mechanisms.Implications: This study identifies a molecular signature of HDV-associated hepatocellular carcinoma and suggests the potential for new biomarkers for early diagnostics. Mol Cancer Res; 16(9); 1406-19. ©2018 AACR.

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Dataset Information

Investigation of the clinical significance and prospective molecular mechanisms of cystatin genes in patients with hepatitis B virus?related hepatocellular carcinoma.

Publications

Investigation of the clinical significance and prospective molecular mechanisms of cystatin genes in patients with hepatitis B virus‑related hepatocellular carcinoma.

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