TMPRSS4 facilitates epithelial-mesenchymal transition of hepatocellular carcinoma and is a predictive marker for poor prognosis of patients after curative resection

Wang, Cheng-Hao; Guo, Zhongyi; Chen, Zeting; Zhi, Xu; Li, Dengke; Dong, Zhao‐Ru; Chen, Zhiqiang; Hu, Sanyuan; Li, Tao

doi:10.1038/srep12366

Cited by 35 publications

(38 citation statements)

References 36 publications

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“…Expression of the serine protease TMPRSS4 is highly increased in a variety of solid tumors and is associated with poor prognosis in some cancer types such as breast, colon, cervix, thyroid and liver [8, 11]. Our present study shows for the first time that TMPRSS4 is an independent prognostic indicator of reduced survival in patients with squamous NSCLC at early stages, thus validating our previous findings by mRNA analysis [7].…”

Section: Discussionsupporting

confidence: 89%

Epigenetic alterations leading to TMPRSS4 promoter hypomethylation and protein overexpression predict poor prognosis in squamous lung cancer patients

et al. 2016

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Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, which highlights the need of innovative therapeutic options. Although targeted therapies can be successfully used in a subset of patients with lung adenocarcinomas (ADC), they are not appropriate for patients with squamous cell carcinomas (SCC). In addition, there is an unmet need for the identification of prognostic biomarkers that can select patients at risk of relapse in early stages. Here, we have used several cohorts of NSCLC patients to analyze the prognostic value of both protein expression and DNA promoter methylation status of the prometastatic serine protease TMPRSS4. Moreover, expression and promoter methylation was evaluated in a panel of 46 lung cancer cell lines. We have demonstrated that a high TMPRSS4 expression is an independent prognostic factor in SCC. Similarly, aberrant hypomethylation in tumors, which correlates with high TMPRSS4 expression, is an independent prognostic predictor in SCC. The inverse correlation between expression and methylation status was also observed in cell lines. In vitro studies showed that treatment of cells lacking TMPRSS4 expression with a demethylating agent significantly increased TMPRSS4 levels. In conclusion, TMPRSS4 is a novel independent prognostic biomarker regulated by epigenetic changes in SCC and a potential therapeutic target in this tumor type, where targeted therapy is still underdeveloped.

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Section: Discussionsupporting

confidence: 89%

Epigenetic alterations leading to TMPRSS4 promoter hypomethylation and protein overexpression predict poor prognosis in squamous lung cancer patients

et al. 2016

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“…Curative resection was defined as complete resection of all tumor nodules and the cut surface being free of cancer by histologic examination; having no cancerous thrombus in the portal vein, hepatic veins, or bile duct; and having no extrahepatic metastasis4647. All pathologic specimens were reviewed by 2 pathologists to confirm the diagnosis of HCC.…”

Section: Discussionmentioning

confidence: 99%

Cholecystectomy is associated with higher risk of early recurrence and poorer survival after curative resection for early stage hepatocellular carcinoma

Wang

Zhi

et al. 2016

Sci Rep

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Although cholecystectomy has been reported to be associated with increased risk of developing hepatocellular carcinoma (HCC), the association between cholecystectomy and prognosis of HCC patients underwent curative resection has never been examined. Through retrospective analysis of the data of 3933 patients underwent curative resection for HCC, we found that cholecystectomy was an independent prognostic factor for recurrence-free survival (RFS) of patients at early stage (BCLC stage 0/A) (p = 0.020, HR: 1.29, 95% CI: 1.04–1.59), and the 1-, 3-, 5-year RFS rates for patients at early stage were significantly worse in cholecystectomy group than in non-cholecystectomy group (80.5%, 61.8%, 52.0% vs 88.2%, 68.8%, 56.8%, p = 0.033). The early recurrence rate of cholecystectomy group was significantly higher than that of non-cholecystectomy group for patients at early stage (59/47 vs 236/333, p = 0.007), but not for patients at advanced stage (BCLC stage C) (p = 0.194). Multivariate analyses showed that cholecystectomy was an independent risk factor for early recurrence (p = 0.005, HR: 1.52, 95% CI: 1.13–2.03) of early stage HCC, but not for late recurrence (p = 0.959). In conclusion, cholecystectomy is an independent predictor for early recurrence and is associated with poorer RFS of early stage HCC. Removal of normal gallbladder during HCC resection may be avoided for early stage patients.

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“…The inclusion and exclusion criteria of the patient cohorts included (a) having a distinctive pathologic diagnosis of HCC, (b) having no anticancer treatment before liver resection, (c) having curative liver resection, (d) having suitable formalin-fixed, paraffin-embedded tissues and (e) having complete clinicopathologic and follow-up data. All patients were followed regularly in the outpatient clinic and were monitored prospectively for recurrence according to a standard protocol as previously described [13][14][15].…”

Section: Patients and Tissue Samplesmentioning

confidence: 99%

“…Tissue microarray (TMA) was constructed as described in our previous studies [13][14][15]. Immunohistochemical staining for TRIM4 was performed on formalin-fixed sample sections from the TMA.…”

Section: Construction Of Tissue Microarrays and Immunohistochemistrymentioning

confidence: 99%

Role of the E3 Ubiquitin Ligase TRIM4 in Predicting the Prognosis of Hepatocellular Carcinoma

Dong¹,

Zhou²,

Sun³

et al. 2020

J. Cancer

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The E3 ubiquitin ligase TRIM4 has been reported to regulate the assembly of the antiviral signalling complex, induce mitochondrial aggregation and sensitize cells to H 2 O 2 -induced death. However, the relationship between TRIM4 and human malignancies, including hepatocellular carcinoma (HCC), is unclear. In this study, we detected the expression of TRIM4 in 134 pairs of HCC tissues and peritumoural tissues and investigated the association of TRIM4 expression with the prognosis of HCC. We found that the TRIM4 expression was much lower in HCC tissues than in peritumoural tissues and was significantly associated with vascular invasion, tumour capsule and Hong Kong Liver Cancer (HKLC) stage. Univariate and multivariate analyses revealed that the TRIM4 expression was an independent prognostic factor for overall survival (OS) and recurrence-free survival (RFS) in our HCC cohort. Patients with higher TRIM4 expression had a lower incidence of intrahepatic recurrence and a higher OS rate (p<0.001 and p<0.01, respectively). These results were further validated in another independent cohort of 200 HCC patients. In conclusion, the TRIM4 level in HCC tissues is an independent prognostic factor for HCC patients. Close clinical monitoring is recommended for patients with low TRIM4 expression.

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TMPRSS4 facilitates epithelial-mesenchymal transition of hepatocellular carcinoma and is a predictive marker for poor prognosis of patients after curative resection

Cited by 35 publications

References 36 publications

Epigenetic alterations leading to TMPRSS4 promoter hypomethylation and protein overexpression predict poor prognosis in squamous lung cancer patients

Epigenetic alterations leading to TMPRSS4 promoter hypomethylation and protein overexpression predict poor prognosis in squamous lung cancer patients

Cholecystectomy is associated with higher risk of early recurrence and poorer survival after curative resection for early stage hepatocellular carcinoma

Role of the E3 Ubiquitin Ligase TRIM4 in Predicting the Prognosis of Hepatocellular Carcinoma

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