Heterogeneity of Epigenetic and Epithelial Mesenchymal Transition Marks in Hepatocellular Carcinoma with Keratin 19 Proficiency

Yokomichi, Naosuke; Nishida, Naoshi; Umeda, Yuzo; Taniguchi, Fumitaka; Yasui, Kohichiroh; Toshima, Toshiaki; Mori, Yuichi; Nyuya, Akihiro; Tanaka, Takehiro; Yamada, Takeshi; Yagi, T.; Fujiwara, Toshiyoshi; Yamaguchi, Yoshiyuki; Goel, Ajay; Kudo, Masatoshi; Nagasaka, Takeshi

doi:10.1159/000490806

Cited by 15 publications

(14 citation statements)

References 34 publications

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“…By comparing the gene expression profiling between the two subtypes, we found that the aggressive Cluster2 tumors had significantly upregulated expression of stemness-related genes such as CA9, EpCAM, MMP9, KRT19, CD24, and PROM1 (CD133). These are well-known markers of stemness traits and are associated with poorer prognostic outcomes in HCC [18,[59][60][61][62]. Based on integrative analysis of genomic and epigenomic data in liver cancer, Woo et al also identified one aggressive cluster of the HCC subtype (iCl1) with the previously mentioned stemness-related genes being on top of the upregulated genes [17], which is similar to our finding.…”

Section: Discussionsupporting

confidence: 90%

Identification of a Subtype of Hepatocellular Carcinoma with Poor Prognosis Based on Expression of Genes within the Glucose Metabolic Pathway

Zhang

Ghoshal

et al. 2019

Cancers

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Hepatocellular carcinoma (HCC) is the most prevalent primary cancer and a highly aggressive liver malignancy. Liver cancer cells reprogram their metabolism to meet their needs for rapid proliferation and tumor growth. In the present study, we investigated the alterations in the expression of the genes involved in glucose metabolic pathways as well as their association with the clinical stage and survival of HCC patients. We found that the expressions of around 30% of genes involved in the glucose metabolic pathway are consistently dysregulated with a predominant down-regulation in HCC tumors. Moreover, the differentially expressed genes are associated with an advanced clinical stage and a poor prognosis. More importantly, unsupervised clustering analysis with the differentially expressed genes that were also associated with overall survival (OS) revealed a subgroup of patients with a worse prognosis including reduced OS, disease specific survival, and recurrence-free survival. This aggressive subtype had significantly increased expression of stemness-related genes and down-regulated metabolic genes, as well as increased immune infiltrates that contribute to a poor prognosis. Collectively, this integrative study indicates that expressions of the glucose metabolic genes could be used as potential prognostic markers and/or therapeutic targets, which might be helpful in developing precise treatment for patients with HCC.

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Section: Discussionsupporting

confidence: 90%

Identification of a Subtype of Hepatocellular Carcinoma with Poor Prognosis Based on Expression of Genes within the Glucose Metabolic Pathway

Zhang

Ghoshal

et al. 2019

Cancers

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“…Nevertheless, it is important to note that HCC can also express cholangiocellular markers, in particular HCC with atypical features such as fibrous stroma, more infiltrative growth and nodal metastasis. 25,59,60 EpCAM positivity is observed in >90% of cholangiocytic differentiation areas and in 10-20% of hepatocellular areas. 25 Finally, if IHC is discordant with the first H&E, it is advised to perform IHC on other slides and to take new tumour samples.…”

Section: Immunohistochemistry Featuresmentioning

confidence: 97%

Combined hepatocellular-cholangiocarcinoma: An update

Beaufrère

Caldéraro²,

Paradis

2021

Journal of Hepatology

111

131

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Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a tumour that exhibits both hepatocytic and biliary differentiation. Classical risk factors for hepatocellular carcinoma (HCC) seem to also predispose patients to the development of cHCC-CCA. The pathological definition of cHCC-CCA has significantly evolved over time. The last 2019 WHO classification highlighted that the diagnosis of cHCC-CCA should be primarily based on morphology using routine stainings, with additional immunostaining used to refine the identification of subtypes. Among them, "intermediate cell carcinoma" is recognised as a specific subtype, while "cholangiolocellular carcinoma" is now considered a subtype of iCCA. Increasing molecular evidence supports the clonal nature of cHCC-CCA and parallels its biphenotypic histological appearance, with genetic alterations that are classically observed in HCC and/or iCCA. That said, the morphological diagnosis of cHCC-CCA is still challenging for radiologists and pathologists, especially on biopsy specimens. Identification of cHCC-CCA's cell of origin remains an area of active research. Its prognosis is generally worse than that of HCC, and similar to that of iCCA. Resection with lymph node dissection is unfortunately the only curative option for patients with cHCC-CCA. Thus, there remains an urgent need to develop specific therapeutic strategies for this unique clinical entity.

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“…In addition to gene mutations that lead to the activation of proto-oncogenes or inactivation of tumor suppressor genes, abnormal alterations in epigenome modi cation also play a key role in the initiation and progression of a variety of cancers, including lung, breast and liver cancer, and CRC [31][32][33][34]. Several studies have indicated that endogenous and exogenous stimulation can reorganize the chromatin structure of cells, resulting in the expression or suppression of abnormal genes, allowing them to obtain the hallmarks of cancer [35,36].…”

Section: Discussionmentioning

confidence: 99%

Expression and prognostic significance of CBX2 in colorectal cancer: Database mining for CBX family members in malignancies

Zhou¹,

Xiong²,

Liu³

et al. 2021

Preprint

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Background: The Chromobox (CBX) domain protein family, a core component of polycomb repressive complexes 1, is involved in transcriptional repression, cell differentiation, and program development by binding to methylated histone tails. Each CBX family member plays a distinct role in various biological processes through their own specific chromatin domains, due to differences in conserved sequences of the CBX proteins. It has been demonstrated that colorectal cancer (CRC) is a multiple-step biological evolutionary process, whereas the roles of the CBX family in CRC remain largely unclear.Methods: In the present study, the expression and prognostic significance of the CBX family in CRC were systematically analyzed through a series of online databases, including Cancer Cell Line Encyclopedia (CCLE), Oncomine, Human Protein Atlas (HPA), and Gene Expression Profiling Interactive Analysis (GEPIA).Results: Most CBX proteins were found to be highly expressed in CRC, but only the elevated expression of CBX2 could be associated with poor prognosis in patients with CRC. Further examination of the role of CBX2 in CRC was performed through several in vitro experiments. CBX2 was overexpressed in CRC cell lines via the CCLE database and the results were verified by RT-qPCR. Moreover, the knockdown of CBX2 significantly suppressed CRC cell proliferation and invasion. Furthermore, the downregulation of CBX2 was found to promote CRC cell apoptosis. Conclusion: Based on these findings, CBX2 may function as an oncogene and potential prognostic biomarker. Thus, the association between the abnormal expression of CBX2 and the initiation of CRC deserves further exploration.

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Heterogeneity of Epigenetic and Epithelial Mesenchymal Transition Marks in Hepatocellular Carcinoma with Keratin 19 Proficiency

Cited by 15 publications

References 34 publications

Identification of a Subtype of Hepatocellular Carcinoma with Poor Prognosis Based on Expression of Genes within the Glucose Metabolic Pathway

Identification of a Subtype of Hepatocellular Carcinoma with Poor Prognosis Based on Expression of Genes within the Glucose Metabolic Pathway

Combined hepatocellular-cholangiocarcinoma: An update

Expression and prognostic significance of CBX2 in colorectal cancer: Database mining for CBX family members in malignancies

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