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Identification of cancer/testis antigen 2 gene as a potential hepatocellular carcinoma therapeutic target by hub gene screening with topological analysis.

ABSTRACT: The 5-year survival rate of hepatocellular carcinoma (HCC) is <20%; thus, identifying new potential therapeutic targets or novel biomarkers for prognosis prediction is crucial. The present study aimed to screen hub genes by constructing protein-protein interaction (PPI) subnetworks using topological analysis methods, as well as reveal their clinical significance through big data analytics and their association with the clinicopathological features. Firstly, the PPI subnetworks were constructed using four topological analysis methods, including the MCC, DMNC, MNC and degree methods, to obtain 6 hub genes. Subsequently, the hub gene cancer/testis antigen 2 (CTAG2), which affects the prognosis of HCC (overall survival, P=0.035), was acquired by analysing clinical data in The Cancer Genome Atlas database. Meanwhile, CTAG2 expression was significantly associated with the age at diagnosis (P=0.003), T stage (P=0.028), TNM stage (P=0.028) and ?-fetoprotein (AFP) expression (P=0.045). Further immunohistochemical analysis of samples collected in our hospital revealed that the expression level of CTAG2 in 46 HCC tissues was significantly higher in comparison with that in paired adjacent tissues. The clinical data indicated that the expression of CTAG2 was significantly correlated with the hepatitis B virus status (P=0.010) and AFP expression (P=0.004). These results were then found to be consistent with the results of big data analytics. Furthermore, Gene Set Enrichment Analysis demonstrated that the function of CTAG2 in HCC may be associated with the cell cycle. Taken together, these findings suggest that CTAG2 may serve as a new potential therapeutic target for HCC patients.

SUBMITTER: Liu J

PROVIDER: S-EPMC6781590 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Identification of cancer/testis antigen 2 gene as a potential hepatocellular carcinoma therapeutic target by hub gene screening with topological analysis.

Liu Jinwei J Yu Zhaojin Z Sun Mingli M Liu Qianqian Q Wei Minjie M Gao Hua H

Oncology letters 20190905 5

The 5-year survival rate of hepatocellular carcinoma (HCC) is <20%; thus, identifying new potential therapeutic targets or novel biomarkers for prognosis prediction is crucial. The present study aimed to screen hub genes by constructing protein-protein interaction (PPI) subnetworks using topological analysis methods, as well as reveal their clinical significance through big data analytics and their association with the clinicopathological features. Firstly, the PPI subnetworks were constructed u ...[more]

PMID: 31611988

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Project description:BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies with poor prognosis. Cancer-testis genes (CTGs) have been vigorously pursued as targets for cancer immunotherapy, but the expressive patterns and functional roles of CTGs remain unclear in ESCC.MethodsA systematic screening strategy was adopted to screen CTGs in ESCC by integrating multiple public databases and RNA expression microarray data from 119 ESCC subjects. For the newly identified ESCC prognosis-associated CTGs, an independent cohort of 118 patients with ESCC was recruited to validate the relationship via immunohistochemistry. Furthermore, functional assays were performed to determine the underlying mechanisms.Findings21 genes were recognized as CTGs, in particular, CDCA5 was aberrantly upregulated in ESCC tissues and significantly associated with poor prognosis (HR = 1.85, 95%CI: 1.14-3.01, P = .013). Immunohistochemical staining confirmed that positive CDCA5 expression was associated with advanced TNM staging and a shorter overall survival rate (45.59% vs 28.00% for CDCA5-/+ subjects, P = 1.86 × 10-3). H3K27 acetylation in CDCA5 promoter might lead to the activation of CDCA5 during ESCC tumorigenesis. Functionally, in vitro assay of gain- and loss-of-function of CDCA5 suggested that CDCA5 could promote ESCC cells proliferation, invasion, migration, apoptosis resistance and reduce chemosensitivity to cisplatin. Moreover, in vivo assay showed that silenced CDCA5 could inhibit tumor growth. Mechanistically, CDCA5 knockdown led to an arrest in G2/M phase and changes in the expression of factors that played fundamental roles in the cell cycle pathway.InterpretationCDCA5 contributed to ESCC progression and might serve as an attractive target for ESCC immunotherapy. FUND: This work was supported by the Natural Science Foundation of Jiangsu Province (No. BK20181083 and BK20181496), Jiangsu Top Expert Program in Six Professions (No. WSW-003 and WSW-007), Major Program of Science and Technology Foundation of Jiangsu Province (No. BE2016790 and BE2018746), Jiangsu Medical Young Talent Project (No. QNRC2016566), the Program of Jiangsu Medical Innovation Team (No. CXTDA2017006), Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX18_1487) and Jiangsu Province 333 Talents Project (No. BRA2017545).

Dataset Information

Identification of cancer/testis antigen 2 gene as a potential hepatocellular carcinoma therapeutic target by hub gene screening with topological analysis.

Publications

Identification of cancer/testis antigen 2 gene as a potential hepatocellular carcinoma therapeutic target by hub gene screening with topological analysis.

Similar Datasets

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