Transcriptional expressions of Chromobox 1/2/3/6/8 as independent indicators for survivals in hepatocellular carcinoma patients

Ning, Gang; Huang, Yanlin; Zhen, Limin; Xu, Wenxiong; Jiao, Qian; Yang, Fan; Wu, Lina; Zheng, Yongyuan; Song, Jie; Wang, Yensheng; Xie, Chan; Peng, Liang

doi:10.18632/aging.101658

Cited by 49 publications

(70 citation statements)

References 54 publications

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“…Gene alterations such as mutations, amplifications and deep deletions have been reported to influence cancer patients outcomes (31,48). We found 9% alteration of VCAN in gastric cancer and this was associated with better outcome in terms of DFS for patients.…”

Section: Discussionmentioning

confidence: 51%

VCAN – A novel prognostic marker for gastric cancer

Binang

Wang

Tewara³

et al. 2019

Preprint

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Background Versican (VCAN) is a large aggregating extracellular matrix proteoglycan implicated in the pathogenesis of most human cancers but its role in gastric cancer is not yet elucidated. We designed the present study to investigate the expression, prognostic value, relationship between genetic alterations and patient’s outcome, disease associations, as well as genetic and protein interactions of VCAN in gastric cancer. Methods Expression of VCAN in tumor and normal tissues was studied with ONCOMINE, UALCAN, and GEPIA databases and the human protein atlas. UALCAN, GEPIA, OncoLnc and Kaplan-Meier plotter were used to assess the prognostic values of VCAN in gastric cancer. Subgroup analysis of the clinical significance of VCAN in gastric cancer was done using Kaplan-Meier plotter. Genetic alterations of VCAN and their associations with patient’s outcome were studied with cBioPortal. Open targets platform was used to study diseases associated with VCAN, GeneMANIA was used to obtain the neighbor genes interaction network of VCAN, and STRING was used to examine VCAN interaction with other proteins. Results VCAN was upregulated and associated with clinical cancer stages. High VCAN expression predicted unfavorable outcome for all patients; subgroup analysis showed worse outcomes for patients treated with surgery or other adjuvants (other than 5-FU based adjuvant) but better outcome for patients treated with 5-FU based adjuvant, associating VCAN expression with chemosensitivity to 5-FU based adjuvants, but chemoresistance to other adjuvants. Genetic alteration of VCAN correlated with a favorable outcome in terms of disease-free survival for patients. Also, open targets platform showed that VCAN is associated with gastric cancer and is a potential therapeutic target for the disease. Finally, interaction of VCAN with neighbor genes and proteins revealed that VCAN interacts with genes and proteins that drive tumorigenesis and cancer progression. Conclusion The results of this study show that VCAN is an oncogene in gastric cancer whose expression can be applied as a biomarker for prognostic prediction, selection of appropriate chemotherapy drugs/monitoring of treatment response, and is a potential therapeutic target for gastric cancer.

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Section: Discussionmentioning

confidence: 51%

VCAN – A novel prognostic marker for gastric cancer

Binang

Wang

Tewara³

et al. 2019

Preprint

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“…International Publisher sorafenib has become the first-line treatment and made the long-term survival of patients possible to some extent. Even so, with the problems of disease progression, drug-resistance, and adverse drug reaction as the therapy progresses, the urgent need for a more potent novel, targeted drug to replace sorafenib remains an increasingly prominent issue [11][12][13][14][15].…”

Section: Ivyspringmentioning

confidence: 99%

Effect of CELSR3 on the Cell Cycle and Apoptosis of Hepatocellular Carcinoma Cells

Xie

Dang

et al. 2020

J. Cancer

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Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) has been reported in cancers but its role and potential molecular mechanism in hepatocellular carcinoma (HCC) is unclear. Therefore, we aimed to investigate the clinical value and molecular mechanism of CELSR3 in HCC using an in vitro experiment, a meta-analysis and bioinformatics. The in vitro experiment determined the promoting effect of CELSR3 in the proliferation, invasion, and migration of HCC cells. CELSR3 knockout causes S-phage arrest in HCC cells. CELSR3 can also inhibit the apoptosis of HCC cells. The expression of the CELSR3 gene and protein was significantly elevated in HCC. Elevated CELSR3 was correlated to the bigger tumor size, higher pathological stage, and the worse overall survival of HCC. Methylation analysis revealed that the hypomethylation of CELSR3 regulated by DNMT1, DNMT3A, and DNMT3B may be the underlying mechanism of upregulated CELSR3. Biological enrichment analysis uncovered that the cell cycle, DNA replication, and PI3K-Akt signaling pathways were important pathways regulated by CELSR3 and its co-expressed genes in HCC. Taken together, upregulated CELSR3 is an important regulator in the progression and prognosis of HCC. The hypomethylation of CELSR3 and its regulation in the cell cycle may be the potential molecular mechanism in HCC.

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“…Differences in mRNA expression levels were compared using Student's t test. The screening conditions were set as follows [13]: data type: mRNA, p value: < 0.01, fold change: ≥ 1.5.…”

Section: Oncomine Databasementioning

confidence: 99%

“…cBioPortal is an online database for exploring and visualizing multidimensional tumor genomics data. The criteria of genomic pro les were set as follows [13]: mutations, mRNA expression z-scores (RNA-seq V2 RSEM), and putative copy-number alterations from GISTIC. Genetic mutations of CYPs, along with overall survival (OS) and disease-free survival (DFS) of patients with HCC, were obtained from this platform.…”

Section: Tcga Database and Cbioportalmentioning

confidence: 99%

Comprehensive Analysis of the Expression and Prognosis of 12 Cytochrome P450s in Human Hepatocellular Carcinoma from the Perspective of Network Pharmacology

Jiang

Wang

et al. 2020

Preprint

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Background: Cytochrome P450s (CYPs) are pivotal drug metabolic enzymes and play a crucial part in the development and prognosis of hepatocellular carcinoma (HCC). Among various CYPs, 12 (CYP1A2, 27A1, 2A6, 2A7, 2B6, 2C8, 2C9, 2E1, 2J2, 3A4, 3A5, and 4A11) are recognized as key therapeutic targets for HCC from the perspective of network pharmacology. However, the gene expression and prognosis of these 12 CYPs in HCC remain obscure.Methods: In the current study, the mRNA expression of these 12 CYPs and survival of patients with HCC were investigated by mining data from ONCOMINE, Kaplan–Meier plotter, UALCAN, Human Protein Atlas, cBioPortal, STRING, and DAVID databases. Network pharmacology analysis of sorafenib for HCC treatment was conducted using data from Therapeutic Target Database, Drugbank, Swiss Target Prediction, STITCH, OncoDB.HCC, Liverome, STRING, and DAVID databases.Results: Results showed that the mRNA expression levels of the 12 CYPs were markedly reduced in HCC and negatively correlated with tumor stages and grades (except for CYP3A5). The high expression level of nine CYPs, namely, CYP27A1, 2A6, 2A7, 2C8, 2C9, 2E1, 3A4, 3A5, and 4A11 was significantly correlated with favorable prognosis in patients with HCC, indicating that they may serve as candidate prognostic biomarkers for HCC. Additionally, overexpression of CYP27A1, CYP2A7, CYP2B6, CYP2C9, and CYP3A5 was markedly correlated with favorable overall survival in HCC patients who received sorafenib therapy. Network pharmacology analysis of the administration of sorafenib for HCC treatment suggested that this drug may exert its antihepatocarcinoma effects by regulating the FoxO and ErbB signaling pathways.Conclusion: Characterization of the expression and prognosis of 12 CYPs in HCC, as well as network pharmacology analysis of HCC treatment via sorafenib, may provide novel insights into the discovery of potential prognostic markers of and therapeutic targets in HCC.

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Transcriptional expressions of Chromobox 1/2/3/6/8 as independent indicators for survivals in hepatocellular carcinoma patients

Cited by 49 publications

References 54 publications

VCAN – A novel prognostic marker for gastric cancer

VCAN – A novel prognostic marker for gastric cancer

Effect of CELSR3 on the Cell Cycle and Apoptosis of Hepatocellular Carcinoma Cells

Comprehensive Analysis of the Expression and Prognosis of 12 Cytochrome P450s in Human Hepatocellular Carcinoma from the Perspective of Network Pharmacology

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