Increased expression of protease-activated receptors 2 indicates poor prognosis in HBV related hepatocellular carcinoma

Chen, Peng; Yang, Na; Liu, Xu; Zhao, Fang; Zhang, Min

doi:10.1186/s13027-019-0256-3

Cited by 4 publications

(4 citation statements)

References 33 publications

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“…This mechanism could be explained by the increased expression of PAR2 in HCC tissues were associated with advanced TNM stage and poor DFS and OS. These findings were consistently observed in the study by Chen, in which PAR2 expression was increased in HBV-related HCC and high PAR2 expression was correlated with both poor DFS and OS [34].…”

Section: Discussionsupporting

confidence: 85%

The Role of Protease-Activated Receptor 2 in Hepatocellular Carcinoma after Hepatectomy

et al. 2021

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Background and Objectives: Protease activated receptor-2 (PAR2) is elevated in a variety of cancers and has been promoted as a potential therapeutic target. However, the clinical and prognostic values of PAR2 in hepatocellular carcinoma (HCC) are poorly characterized. This study aimed to evaluate the expression of PAR2 in HCC tissues and examine the prognostic value of PAR2 after resection in HCC. Materials and Methods: Two hundred and eight resected specimens were collected from HCC patients at Kaohsiung Chang Gung Memorial Hospital. PAR2 protein expression was assessed by western blotting in HCC tissues and matched normal tissues. The correlation between PAR2 expression and clinicopathological parameters was analyzed. Disease-free survival (DFS) and overall survival (OS) were compared using the log-rank test. A Cox regression model was used to identify independent prognostic factors. Results: PAR2 was expressed at higher levels in HCC tissues than the paired adjacent nontumor tissues. High expression of PAR2 was associated with advanced tumor, node, metastasis (TNM )stage and histological grade. Kaplan-Meier analysis indicated high PAR2 expression was associated with poorer DFS and OS compared to low PAR2 expression. Multivariate analyses indicated high PAR2 expression [hazard ratio (HR), 1.779, p = 0.006), α-fetoprotein (AFP) (HR, 1.696, p = 0.003), liver cirrhosis (HR, 1.735, p = 0.002), and advanced TNM stage (HR, 2.061, p < 0.001) were prognostic factors for DFS, and advanced TNM stage (HR, 2.741, p < 0.001) and histological grade (HR, 2.675, p = 0.002) and high PAR2 expression (HR, 1.832, p = 0.012) were significant risk factors for OS. In subgroup analyses, the combination of PAR2 expression and serum AFP provided improved prognostic ability for OS and DFS. Conclusion: Combination PAR2 and AFP predict HCC outcomes after resection. PAR2 represents a potentially clinically relevant biomarker for HCC.

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Section: Discussionsupporting

confidence: 85%

The Role of Protease-Activated Receptor 2 in Hepatocellular Carcinoma after Hepatectomy

et al. 2021

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“…Trypsin is a serine protease that acts on the protease-activated receptor (PAR) family of plasma membrane receptors which initiates a signalling cascade downstream of phospholipase C activation, resulting in the production of IP3 and movement of Ca 2+ from intracellular stores via IP3 receptors [38]. Altered function of trypsin and PAR2 has been reported in different malignant tissues and cell lines including those of breast, colon, and liver cancers in which PAR expression is reported to be higher than in non-cancerous tissues or cell lines [39][40][41][42]. Trypsin, through interaction with PAR2, was reported to increase cancer cell proliferation and invasion [40,43].…”

Section: Discussionmentioning

confidence: 99%

Pharmacological characterisation of store‑operated calcium entry in medulloblastoma cell lines

Sedeeq¹,

Dutta²,

Maklad³

et al. 2023

Preprint

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Store-operated Ca2+ entry (SOCE) is the primary pathway of Ca2+ entry into mammalian cells. Re-modelling of the SOCE pathway has been suggested as the driving mechanism for many tumour phenotypes, such as cancer cell proliferation, migration, and metastasis. Although SOCE has been studied in many cancer types, calcium signalling, especially the SOCE pathway, is largely unexplored in medulloblastoma (MB). MB is the most common malignant paediatric brain tumour, and previously, we reported that some key SOCE components are upregulated in MB. The present study aimed to functionally characterise SOCE in MB cells. Using RT-PCR, the expression of different SOCE-regulating genes was examined cells of different MB subgroups. Our data indicate that specific subgroups of MB cells differentially express SOCE genes. For example, one key regulatory gene, ORAI1, showed a higher expression in the invasive MB subgroups 3. This difference was also reflected by a higher SOCE in these cells compared to cells from MB subgroups associated with lower invasive potential. Overall, the results highlight that distinct MB subgroups rely on differential gene expression that affects their SOCE activity. Future studies will require a functional characterisation to delineate if altered SOCE is causal for the invasiveness of MB, which will be a critical to understand the potential of SOCE as a therapeutic target for the treatment of MB.

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“… 27 More importantly, PAR2 is also shown to participate in HBV infection-related complications. 28 , 29 High expression of PAR2 in HCC patients means the relatively low survival rate. 28 PAR2 pepducin inhibitors administration can effectively repress liver fibrosis in a mouse model.…”

Section: Introductionmentioning

confidence: 99%

“… 28 , 29 High expression of PAR2 in HCC patients means the relatively low survival rate. 28 PAR2 pepducin inhibitors administration can effectively repress liver fibrosis in a mouse model. 29 However, studies on the interaction of PAR2 with HBx-induced liver injury are relatively rare.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Protease Activated Receptor 2 Attenuates HBx-Induced Inflammation and Mitochondria Oxidative Stress

B¹,

Y²,

S³

et al. 2022

IDR

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Background Hepatitis B virus (HBV) infection is one of the global public problems. Among the known infection cases, HBV X protein (HBx) is one of the key inducements of viral replication and host infection. This study was aimed to uncover the role of protease activated receptor 2 (PAR2) on HBx-induced liver injury. Methods A PAR2-KO mouse model expressing HBx was constructed using hydrodynamics-based in vivo gene transfection method. In addition, pcDNA3.1-HBx was used to over-express HBx in LO 2 cells. The effects of HBx overexpression on inflammation and mitochondria oxidative stress were evaluated. Results We found that PAR2 protein level was increased by HBx overexpression. The enforced HBx inhibited LO 2 cells apoptosis. Meanwhile, HBx induced inflammation reactions through promoting the secretion of pro-inflammatory cytokines such as TNF-α, IL-6, and CXCL-2. Overexpressed HBx also resulted in mitochondria oxidative stress by upregulation of ROS level and downregulation of MMP and ATP. However, in FSLLRY-NH 2 (PAR2 antagonist) treated LO 2 cells or PAR2-KO mice, PAR2 blockade reversed the above adverse effects of HBx on liver cells or tissues. Conclusion Inhibition of PAR2 may suppress inflammation and mitochondria oxidative stress caused by HBx, pointing out the potential application values of PAR2 antagonist on the treatment of HBV infection in clinic.

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Increased expression of protease-activated receptors 2 indicates poor prognosis in HBV related hepatocellular carcinoma

Cited by 4 publications

References 33 publications

The Role of Protease-Activated Receptor 2 in Hepatocellular Carcinoma after Hepatectomy

The Role of Protease-Activated Receptor 2 in Hepatocellular Carcinoma after Hepatectomy

Pharmacological characterisation of store‑operated calcium entry in medulloblastoma cell lines

Inhibition of Protease Activated Receptor 2 Attenuates HBx-Induced Inflammation and Mitochondria Oxidative Stress

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