FAM83D associates with high tumor recurrence after liver transplantation involving expansion of CD44+ carcinoma stem cells

Lin, Bin-Yi; Chen, Tianchi; Zhang, Qi‐Jun; Lu, Xiaoxiao; Zheng, Zhiyun; Ding, Jun; Liu, Jinfeng; Yang, Zhe; Geng, Lei; Wu, Liming; Zhou, Lin; Zheng, Shusen

doi:10.18632/oncotarget.12715

Cited by 18 publications

(19 citation statements)

References 41 publications

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“…Therefore, these two genes might have better predictive ability to identify HCV-HCC at early stage on the background of HCV-cirrhosis. Consistent with our nding, CDKN3 and FAM83D were important regulators of cell cycle, and studies had also shown that they were highly expressed in tumor tissues compared to normal tissues, and overexpression of CDKN3 and FAM83D was correlated with the poor outcome in HCC patients [24,[29][30][31][32][33]. However, studies focusing on the role of these two genes in HCV-HCC occurrence and progression on the background of HCV-cirrhosis are limited.…”

Section: Disscusionsupporting

confidence: 86%

Identification of Key Genes in HCV-induced HCC at Early Stage on the Background of HCV-cirrhosis

nie

et al. 2020

Preprint

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Background: Hepatocellular carcinoma (HCC) is one of the most common and deadly malignant tumors worldwide. Hepatitis C virus (HCV)-induced cirrhosis (HCV-cirrhosis) is one of the leading causes of HCC occurrence. Due to the lack of effective biomarkers, most patients with HCV-induced HCC (HCV-HCC) are at advanced stages when they are first diagnosed. Our study aims to employ transcriptomic profiling dataset to identify potential biomarkers that can predict HCV-HCC at early stage on the background of HCV-cirrhosis. Methods: The dataset incorporating HCV-cirrhosis and HCV-HCC subjects at different stages from Gene Expression Omnibus was analyzed to identify gene signature-related to HCV-HCC on the background of HCV-cirrhosis. Multiple-genes based risk score-related prediction model was established to predict HCV-HCC samples at different stages, and receiver-operating characteristic (ROC) curve analysis was used to select the best cutoff value of risk scores for prediction and to evaluate the prediction model. Samples with risk scores higher than cutoff value were defined as high score group.Results: Highly clustered 20 genes were identified and were all gradually increased as HCV-HCC progressed from HCV-cirrhosis to very advanced HCC. Compared with HCV-cirrhosis, the prevalence of HCV-HCC at any of the stages in high score group was 100%. The risk score-related prediction model based on the 20 genes-biomarker got the accuracy of over 95.2 % with area under ROC (AUC) over 0.94. To implement the biomarker easily in real life and make it economical, we tried to limit the gene numbers. Interestingly, CDKN3 and FAM83D were significantly decreased in HCV-cirrhosis tissues as compared to normal tissues and then increased as HCV-HCC progressed. The results were attractive that the prediction model based on this 2 genes-biomarker indicated that prevalence of HCV-HCC in high score group was still 100% and got the predictive accuracy of over 95.2 % with AUC over 0.96, revealing even a better performance.Conclusion: Our study indicated a 2-genes-based biomarker that could identify HCV-HCC at earlier stages on the background of HCV-cirrhosis, which might be a promising biomarker for early diagnosis of HCV-HCC and potential novel treatment target.

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Section: Disscusionsupporting

confidence: 86%

Identification of Key Genes in HCV-induced HCC at Early Stage on the Background of HCV-cirrhosis

nie

et al. 2020

Preprint

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“…ALDH1 activation and high CD44 expression have also been reported as markers to identify cell populations enriched for CSCs in breast cancer, gastric cancer and lung cancer . In general, only a minority of cells (<5%) in the total tumour cell population are believed to be stem cells, but the flow cytometric analysis of several studies revealed that the percentage of cells expressing CD133, CD44 or ALDH1 differed between several HCC cell lines (from <1% to more than 90%) . In our study, the results shown in Figure indicate that more cells with high CPA4 expression expressed stem cell markers; more Bel7402 cells expressed stem cell markers than HepG2 cells.…”

Section: Discussionsupporting

confidence: 60%

“…28 In general, only a minority of cells (<5%) in the total tumour cell population are believed to be stem cells, but the flow cytometric analysis of several studies revealed that the percentage of cells expressing CD133, CD44 or ALDH1 differed between several HCC cell lines (from <1% to more than 90%). [29][30][31] In our study, the results shown in Figure 3 indicate that more cells with high CPA4 expression expressed stem cell markers; more Bel7402 cells expressed stem cell markers than HepG2 cells. Transfection with CPA4 plasmids increased stem cell marker expression, indicating that CPA4 may induce the proportion of stem cell marker-expressing cells.…”

Section: Discussionsupporting

confidence: 53%

Carboxypeptidase A4 promotes proliferation and stem cell characteristics of hepatocellular carcinoma

Zhang

Wang

Shang

et al. 2019

Int J Experimental Path

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Summary Carboxypeptidase A4 (CPA4), a member of the metallo‐carboxypeptidase family, is overexpressed in liver cancer and is associated with cancer progression. The role of CPA4 in hepatocellular carcinoma (HCC) remains unclear. In this study, we aimed to evaluate the relevance of CPA4 to the proliferation and expression of stem cell characteristics of hepatocellular carcinoma cells. Western blot analysis showed high CPA4 expression in the liver cancer cell line Bel7402 and low expression in HepG2 cells. Knock‐down of CPA4 decreased cancer cell proliferation as detected by MTT and clone formation assays. The serum‐free culture system revealed that downregulated CPA4 suppressed the sphere formation capacities of tumour cells. However, upregulated CPA4 increased the proliferation and sphere formation capacity. In addition, the protein expression of CD133, ALDH1 and CD44 also increased in cells with upregulated CPA4. In vivo, the overexpression of CPA4 in tumour cells that were subcutaneously injected into nude mice markedly increased the growth of the tumours. These data suggest that CPA4 expression leads to poor prognoses by regulating tumour proliferation and the expression of stem cell characteristics and may therefore serve as a potential therapeutic target of HCC.

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“…CD44/CD24 has been reported to drive CSC progression in different cancer types [26] , [27] , [28] . We detected the influence of BPTF on their expression level in HCC cells.…”

Section: Resultsmentioning

confidence: 99%

BPTF promotes hepatocellular carcinoma growth by modulating hTERT signaling and cancer stem cell traits

Zhao

Zheng

et al. 2019

Redox Biology

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Bromodomain PHD finger transcription factor (BPTF), a core subunit of nucleosome-remodeling factor (NURF) complex, plays an important role in chromatin remodeling. However, its precise function and molecular mechanism involved in hepatocellular carcinoma (HCC) growth are still poorly defined. Here, we demonstrated the tumor-promoting role of BPTF in HCC progression. BPTF was highly expressed in HCC cells and tumor tissues of HCC patients compared with normal liver cells and tissues. Knockdown of BPTF inhibited cell proliferation, colony formation and stem cell-like traits in HCC cells. In addition, BPTF knockdown effectively sensitized the anti-tumor effect of chemotherapeutic drugs and induced more apoptosis in HCC cells. Consistently, knockdown of BPTF in a xenograft mouse model also suppressed tumor growth and metastasis accompanied by the suppression of cancer stem cells (CSC)-related protein markers. Moreover, the mechanism study showed that the tumor-promoting role of BPTF in HCC was realized by transcriptionally regulating the expression of human telomerase reverse transcriptase (hTERT). Furthermore, we found that HCC patients with high BPTF expression displayed high hTERT expression, and high BPTF or hTERT expression level was positively correlated with advanced malignancy and poor prognosis in HCC patients. Collectively, our results demonstrate that BPTF promotes HCC growth by targeting hTERT and suggest that the BPTF-hTERT axis maybe a novel and potential therapeutic target in HCC.

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FAM83D associates with high tumor recurrence after liver transplantation involving expansion of CD44+ carcinoma stem cells

Cited by 18 publications

References 41 publications

Identification of Key Genes in HCV-induced HCC at Early Stage on the Background of HCV-cirrhosis

Identification of Key Genes in HCV-induced HCC at Early Stage on the Background of HCV-cirrhosis

Carboxypeptidase A4 promotes proliferation and stem cell characteristics of hepatocellular carcinoma

BPTF promotes hepatocellular carcinoma growth by modulating hTERT signaling and cancer stem cell traits

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