Biology subjects

Zhang, Z.-y.

Publications and source records attributed to Zhang, Z.-y..

3 recordsLinked to original sources

bioRxiv2024

Prognostic Significance of preoperative serum CA125, CA19-9, CA72-4, CEA, and AFP in Patients with Endometrial cancer

ObjectiveTo determine preoperative serum CA125, CA19-9, CA72-4, CEA, and AFP with prognostic value, and to establish a risk score based on CA125, CEA, AFP levels for predicting the overall survival (OS) and progression-free survival (PFS) of endometrial cancer (EC) patients. MethodsA retrospective cohort study with 2081 EC patients was conducted at Shengjing Hospital of China Medical University. Patient baseline information, tumor characteristics, and data on five serum biomarkers (CA125, CA19-9, CA72-4, CEA, and AFP) were collected. Hazard ratios (HRs) and 95% confidence intervals (CIs) were determined using univariate or multivariate Cox proportional hazard models. log-rank test and Kaplan-Meier analysis were used to compared survival, Data were randomly divided into a training cohort (50%, N = 1041) and an external validation cohort (50%, n = 1040). the least absolute shrinkage and selection operator (Lasso)-Cox regression model was used to screen the independent factors for establishing risk score. And develop nomograms for survival rate prediction. ResultsMultivariate analysis showed Elevated CA125 (P<0.0001) AFP (P <0.0001) and CEA(P=0.037) were identified as independent biomarkers for PFS. Increased CA125 (P = 0.003) AFP (P <0.0001) and CEA(P=0.014) were independent factors associated with OS. CA125, AFP and CEA were thus incorporated in an innovative Risk score (RS) by Lasso-Cox regression model, The RS was also an independent indicator for PFS (P<0.0001) and OS (P<0.0001). Furthermore, we developed and validated nomogram based on Cox regression models. The discriminative ability and calibration of the nomograms revealed good predictive ability, as indicated by the calibration plots. ConclusionThis study suggests that the risk score based on preoperative serum levels of CA125, CEA, and AFP was prognostic biomarkers for predicting progression-free survival and overall survival for EC patients. Nomograms based on the RS and clinicopathological features accurately predict Prognosis of EC patients.

cancer biology↗

bioRxiv2019

PTP-MEG2 regulates quantal size and fusion pore opening through two distinct structural bases and substrates

Tyrosine phosphorylation of secretion machinery proteins is a crucial regulatory mechanism for exocytosis. However, the participation of protein tyrosine phosphatases (PTPs) in different exocytosis stages has not been defined. Here we demonstrated that PTP-MEG2 controls multiple steps of catecholamine secretion. Biochemical and crystallographic analyses revealed key residues that the interactions between govern the PTP-MEG2 and NSF-pY83 site, specify PTP-MEG2 substrate selectivity and modulate the fusion of catecholamine-containing vesicles. Unexpectedly, delineation of PTP-MEG2 mutants along with the NSF binding interface revealed that PTP-MEG2 controls the fusion pore opening through non-NSF dependent mechanisms. Utilizing bioinformatics search and biochemical and electrochemical screening approaches, we discovered that PTP-MEG2 regulates the opening and extension of the fusion pore by dephosphorylating the DYNAMIN2-pY125 and MUNC18-1-pY145 site. Further structural and biochemical analysis confirmed the interaction of PTP-MEG2 with MUNC18-1-pY145 or DYNAMIN2-pY125 through a distinct structural basis compared with that of the NSF-pY83 site. Our studies extended mechanistic insights in complex exocytosis processes. HIGHLIGHTSPTP-MEG2 regulates multiple steps of exocytosis. A crystal structure of the PTP-MEG2/phosphor-NSF-pY83 segment was obtained. Functional delineation of the PTP-MEG2/NSF interface led to the discovery of new PTP-MEG2 substrates. PTP-MEG2 regulates fusion pore opening and extension through the DYNAMIN2-pY125 site and MUNC18-1 pY145 site. The distinct structural basis of the recognition of substrates by PTP-MEG2 allows selective inhibitor design.

cell biology↗

bioRxiv2018

Influence of miR-520e-mediated MAPK signaling pathway on HBV replication and regulation of hepatocellular carcinoma cells via targeting EphA2

This paper aims to determine the role of miR-520e in the replication of hepatitis B virus (HBV) and the growth of hepatocellular carcinoma (HCC) cells. MiR-520e and EphA2 in HBV-positive HCC tissues and cells were detected. HepG2.2.15 and Huh7 cells transfected with pHBV1.2 were divided into Mock, NC, miR-520e mimic, miR-520e inhibitor, si-EphA2, and miR-520e inhibitor + si-EphA2 groups. MiR-520e, HBV DNA content, HBsAg and HBeAg levels, cell proliferation, apoptosis and protein expression of EphA2 and MAPK pathways were evaluated. Furthermore, rAAV81.3HBV infected-mouse model was established to detect HBV-DNA levels. MiR-520e was up-regulated and EphA2 was down-regulated in HBV-positive HCC tissues and cells (HepG2.2.15 and HepAD38). MiR-520e was decreased in Huh7-X and HepG2-X cells in which HBx was stably expressed, but miR-520e was dose-dependently elevated in Huh7-X, HepG2-X, and HepG2.2.15 cells after interfering HBx. Additionally, miR-520e mimic and si-EphA2 groups were apparently reduced in HBV DNA content, HBsAg and HBeAg levels, cell proliferation, and were enhanced in the expressions of EphA2, MAPK pathways and cell apoptosis. Furthermore, si-EphA2 can reverse the promotion effect of miR-520e inhibitor on the HBV replication and tumor cell growth Up-regulating miR-520e in rAAV81.3HBV infected-mouse resulted in the reduced EphA2 in liver tissues and HBV DNA content in serum. MiR-520e was found to be decreased in HBV-positive HCC tissues and cells, while over-expression of miR-520e blocked MAPK pathways via inhibiting EphA2, ultimately reducing HBV replication and inhibiting tumor cell growth.

cancer biology↗