Plexin domain-containing 1 may be a biomarker of poor prognosis in hepatocellular carcinoma patients,may mediate immune evasion

BACKGROUND For the first time,we investigated the oncological role of plexin domain-containing 1(PLXDC1),also known as tumor endothelial marker 7(TEM7),in hepatocellular carcinoma(HCC).AIM To investigate the oncological profile of PLXDC1 in HCC.METHODS Based on The Cancer Genome Atlas database,we analyzed the expression of PLXDC1 in HCC.Using immunohistochemistry,quantitative real-time polymerase chain reaction(qRT-PCR),and Western blotting,we validated our results.The prognostic value of PLXDC1 in HCC was analyzed by assessing its correlation with clinicopathological features,such as patient survival,methylation level,tumor immune microenvironment features,and immune cell surface checkpoint expression.Finally,to assess the immune evasion potential of PLXDC1 in HCC,we used the tumor immune dysfunction and exclusion(TIDE)website and immunohistochemical staining assays.RESULTS Based on immunohistochemistry,qRT-PCR,and Western blot assays,overexpression of PLXDC1 in HCC was associated with poor prognosis.Univariate and multivariate Cox analyses indicated that PLXDC1 might be an independent prognostic factor.In HCC patients with high methylation levels,the prognosis was worse than in patients with low methylation levels.Pathway enrichment analysis of HCC tissues indicated that genes upregulated in the high-PLXDC1 subgroup were enriched in mesenchymal and immune activation signaling,and TIDE assessment showed that the risk of immune evasion was significantly higher in the high-PLXDC1 subgroup compared to the low-PLXDC1 subgroup.The high-risk group had a significantly lower immune evasion rate as well as a poor prognosis,and PLXDC1-related risk scores were also associated with a poor prognosis.CONCLUSION As a result of this study analyzing PLXDC1 from multiple biological perspectives,it was revealed that it is a biomarker of poor prognosis for HCC patients,and that it plays a role in determining immune evasion status.

Influence of hydrogen sulfide on zymogen activation of homocysteineinduced matix metalloproteinase-2 in H9C2 cardiocytes

Objective: To observe the influence of different concentrations of homocysteine(Hcy) and hydrogen sulfide(H2S) on the secretion and activation of matix metalloproteinase-2(MMP-2) in cardiocytes so as to search for new ways to fight against myocardial tissue fibrosis. Methods: Cardiocytes H9C2 was cultured in vitro and different concentrations of Hcy and H2 S were added for 6-h and 24-h cultivation. MTT cell proliferation assay was applied to test the activation change of cardiocytes H9C2 after affecting by different concentrations of Hcy and H2 S. ELISA and MTT were employed to detect the expression and enzymatic activity of MMP-2. Results: The H9C2 cell inhibition of activity was more significant with 1 000 μmol/L of Hcy as compared with other concentrations(P<0.001). With 2.5-100.0 μmol/L Hcy and 0.1, 1.0 and 10.0 mmol/L H2 S, the activity of H9C2 did not change significantly(P>0.05). Hcy with concentrations of 10, 50 and 100 μmol/L could increase the quantity of MMP-2 secreted by cardiocytes H9C2, and the interaction strength was concentration-dependent(P<0.05). After interacting with 100 μmol/L of Hcy for 6 h, the zymogen activation effect of MMP-2 was stronger than that of the 2.5-25 μmol/L group(P<0.05). After interacting with Hcy and H2S(1.0 mmol/L) for 6 h and 24 h, the activation effect of MMP-2 was stronger than those interacted with 10, 25, 50 and 100 μmol/L of Hcy(P<0.05). Conclusions: Hcy can increase the production of MMP-2 secreted by H9C2 cell and improve its zymogen activation. Besides, the interaction strength is concentration-dependent; while H2 S can up-regulate the activation of MMP-2 and co-promote the activation of MMP-2 with Hcy as well.