Prognostic value of aberrantly expressed methylation genes in human hepatocellular carcinoma

Zhen, Limin; Ning, Gang; Wu, Lina; Zheng, Yongyuan; Yang, Fan; Chen, Tongtong; Xu, Wenxiong; Liu, Ying; Xie, Chan; Peng, Liang

doi:10.1042/bsr20192593

Cited by 8 publications

(3 citation statements)

References 58 publications

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“…Surgical resection and liver transplantation remain the primary therapy for HCC [19,20]. However, only 15 to 25 percent of patients bene t from procedures, and 70 percent recur after resection [21]. The current 5-year survival rate is below than 20% [22].…”

Section: Discussionmentioning

confidence: 99%

HBx promotes tumorigenicity through RRM2-mediated autophagy in hepatocellular carcinoma

wang,

yaqun,

Wang

et al. 2023

Preprint

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HBV infection can exacerbate liver disease progression through multiple mechanisms, eventually leading to hepatocellular carcinoma (HCC). HBV-encoded oncogene X protein (HBx), a key regulatory protein of HBV infection, serves as a positive regulator of hepatocarcinogenesis. Ribonucleotide-diphosphate reductase M2 subunit (RRM2), which is indispensable for DNA replication and repair, has been shown overexpressed in a range of malignancies. Our previous studies clarified that RRM2 expression is highly elevated in HCC, particularly in HBV-related HCC. Given the robust RRM2 expression is strongly associated with poor survival rate of the patients with HCC, while the specific functions and underlying mechanisms of RRM2 in HBV-related HCC remain elusive; the present study was performed to elucidate whether HBx increases RRM2 expression, and whether RRM2 engages in interaction with HBx in vivo and in vitro. Autophagy is a crucial step in the oncogenic process of HBx, while autophagy inhibition attenuates HBx-initiated proliferation response. We further demonstrated that RRM2 interference lowered HBx-induced autophagy, inhibited the production of autophagic vesicles and lysosomes, and caused G1/S blockage, thereby inhibiting HBx-stimulated hepatocellular carcinogenesis. Our findings indicate that RRM2 may play a tumor-promoting role in HBV-associated HCC by modulating autophagy, suggesting that RRM2 may be a potential therapeutic target for HCC.

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Section: Discussionmentioning

confidence: 99%

HBx promotes tumorigenicity through RRM2-mediated autophagy in hepatocellular carcinoma

wang,

yaqun,

Wang

et al. 2023

Preprint

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“…Potential marker gene CDC5L codes a DNA-binding protein involved in cell cycle regulation, and complexing with PRP19 participates in response to DNA damage [ 35 ]. It has been implicated in bladder cancer, prostate cancer, and hepatocellular carcinoma tumorigenesis [ 36 , 37 , 38 ]. According to the Mouse Genomics database, Cdc5l −/− mice led to preweaning lethality or embryonic lethality.…”

Section: Discussionmentioning

confidence: 99%

Integrated Bioinformatics Analysis Reveals Marker Genes and Potential Therapeutic Targets for Pulmonary Arterial Hypertension

Zhang

et al. 2021

Genes

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Pulmonary arterial hypertension (PAH) is a rare cardiovascular disease with very high mortality rate. The currently available therapeutic strategies, which improve symptoms, cannot fundamentally reverse the condition. Thus, new therapeutic strategies need to be established. Our research analyzed three microarray datasets of lung tissues from human PAH samples retrieved from the Gene Expression Omnibus (GEO) database. We combined two datasets for subsequent analyses, with the batch effects removed. In the merged dataset, 542 DEGs were identified and the key module relevant to PAH was selected using WGCNA. GO and KEGG analyses of DEGs and the key module indicated that the pre-ribosome, ribosome biogenesis, centriole, ATPase activity, helicase activity, hypertrophic cardiomyopathy, melanoma, and dilated cardiomyopathy pathways are involved in PAH. With the filtering standard (|MM| > 0.95 and |GS| > 0.90), 70 hub genes were identified. Subsequently, five candidate marker genes (CDC5L, AP3B1, ZFYVE16, DDX46, and PHAX) in the key module were found through overlapping with the top thirty genes calculated by two different methods in CytoHubb. Two of them (CDC5L and DDX46) were found to be significantly upregulated both in the merged dataset and the validating dataset in PAH patients. Meanwhile, expression of the selected genes in lung from PAH chicken measured by qRT-PCR and the ROC curve analyses further verified the potential marker genes’ predictive value for PAH. In conclusion, CDC5L and DDX46 may be marker genes and potential therapeutic targets for PAH.

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“…Altering the methylation status of these genes might be therapeutic targets for hepatocellular carcinoma. 34 In order to elucidate the underlying mechanism of PLAUR in BLCA, we examined the relationship between PLAUR expression, the promoter methylation level and clinicopathological features of BLCA patients by using cBioPortal and UALCAN databases. The results indicated that the expression of PLAUR was negatively correlated with its promoter methylation level, which was significantly decreased in BLCA.…”

Section: Discussionmentioning

confidence: 99%

PLAUR as a Potential Biomarker Associated with Immune Infiltration in Bladder Urothelial Carcinoma

Liu¹,

Chen²,

Zhang³

et al. 2021

JIR

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Background Bladder urothelial carcinoma (BLCA) is one of the most lethal and aggressive malignancies of genitourinary system that affects human health. The urokinase plasminogen activator receptor (PLAUR) plays essential roles in tumorigenesis and immune modulation, and its aberrant expression is closely correlated with cancer progression. However, whether PLAUR has the potential to be one promising biomarker or immunotherapy target for BLCA is unknown. Methodology Various online databases were applied to assess the expression profile and prognostic value of PLAUR, as well as its correlation with immune infiltration in BLCA, including Oncomine, PrognoScan, TCGA, cBioPortal, TIMER, TISIDB, UALCAN, and MethSurv. The expression of PLAUR in BLCA was confirmed with ELISA assay for serum samples and immunohistochemistry for tissue samples. Results The results showed that the expression of PLAUR was elevated in BLCA, which was further confirmed by ELISA and immunohistochemistry. Patients with higher PLAUR level were predicted to have lower overall survival and disease specific survival rates, which were not impacted by the genetic alterations of PLAUR. In addition, the expression of PLAUR was positively associated with immune infiltration, and also the expression levels of gene markers of various immune cells. The negative correlation between PLAUR expression and PLAUR methylation level was observed, among which PLAUR expression was positively correlated with the abundance of 28 kinds of tumor-infiltrating lymphocytes, while PLAUR methylation level was negatively correlated with the abundance of 11 types of tumor-infiltrating lymphocytes. Moreover, the methylation level of PLAUR was closely correlated with patients’ clinicopathological features, and hypomethylation of PLAUR was associated with better outcomes of BLCA patients. Conclusion These findings suggested that PLAUR had the potential to serve as a valuable detection and prognostic biomarker or immunotherapeutic target for BLCA.

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Prognostic value of aberrantly expressed methylation genes in human hepatocellular carcinoma

Cited by 8 publications

References 58 publications

HBx promotes tumorigenicity through RRM2-mediated autophagy in hepatocellular carcinoma

HBx promotes tumorigenicity through RRM2-mediated autophagy in hepatocellular carcinoma

Integrated Bioinformatics Analysis Reveals Marker Genes and Potential Therapeutic Targets for Pulmonary Arterial Hypertension

PLAUR as a Potential Biomarker Associated with Immune Infiltration in Bladder Urothelial Carcinoma

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