Aim:Scavenger receptor class B,type I(SR-BI)is an integral plasma membrane protein that has been reported to be overexpressed in various malignancies,such as renal cancer,breast cancer,and prostate cancer,and is an in...Aim:Scavenger receptor class B,type I(SR-BI)is an integral plasma membrane protein that has been reported to be overexpressed in various malignancies,such as renal cancer,breast cancer,and prostate cancer,and is an independent prognostic factor.However,the clinical value and expression of SR-BI in GC are unknown.Our research aimed to explore the role of SR-BI in combination with immune markers as a diagnostic and prognostic marker for gastric cancer(GC).Methods:GC tissues,paracancerous tissues,and clinicopathological data of 149 patients were collected.The expression level of SR-BI,Tumor-infiltrating lymphocytes(TILs),and PD-L1 were evaluated by immunohistochemistry(IHC).The associations of the SR-BI staining intensity with clinicopathological features and immune markers were determined by the chi-square test.Univariate and multivariate COX regression analyses were used to evaluate independent prognostic factors.Kaplan–Meier analyses were performed to plot the survival curve.Results:Our results indicated that SR-BI was expressed at higher levels in tumor tissues than in adjacent paracancerous tissues(p<0.001),and patients with high levels of SR-BI expression had a worse prognosis.Univariate and multivariate analyses revealed that high SR-BI expression was an independent factor for poor prognosis.The chi-square test determined that the expression of SR-BI was negatively correlated with CD4+T cells and CD8+T cells(CD4+T cells,p=0.013;CD8+T cells,p=0.021),and positively correlated with PD-L1(p=0.022).Finally,survival analysis revealed that CD4+T cells were associated with the prognosis of GC patients(p=0.019),and the combined survival analysis of SR-BI and CD4+T cells was also statistically significant(p=0.030).Conclusion:SR-BI is highly expressed in GC tissue and associated with poor prognosis.Moreover,SR-BI can also regulate the GC tumor immune microenvironment.展开更多
Zebrafish hematopoietic stem and progenitor cells（HSPCs） originate from the hemogenic endothelium of the ventral wall of the dorsal aorta（DA） through the endothelial-to-hematopoietic transition（EHT） from approxi...Zebrafish hematopoietic stem and progenitor cells（HSPCs） originate from the hemogenic endothelium of the ventral wall of the dorsal aorta（DA） through the endothelial-to-hematopoietic transition（EHT） from approximately 30 to 60 hours post fertilization（hpf）. However, whether other artery sites can generate HSPCs de novo remains unclear. In this study, using live imaging and lineage tracing, we found that the caudal dorsal artery（CDA） in the caudal hematopoietic tissue directly gave rise to HSPCs through EHT.This process initiated from approximately 60 hpf and terminated at approximately 156 hpf. Compared with that in the DA, fewer EHT events were observed in the CDA. The EHT events in the DA and CDA were similarly regulated by Runx1 but differentially influenced by blood flow（i.e., the EHT frequency in CDA was affected to a lesser extent when circulation was compromised in the tnnt2a～（-/-）mutant）. Therefore,the whole artery, including both DA and CDA, was endowed with the ability to produce HSPCs during a much longer time period. Coincidently, the lineage tracing results indicated that adult hematopoietic cells originated from the embryonic endothelium, and those produced later preferentially colonized the adult thymus. Collectively, our study revealed that the CDA serves as an additional source of hematopoiesis, and it shows similar but not identical properties with the DA.展开更多
基金supported by the Natural Science Foundation of Zhejiang Province(HDMY22H160008)the Medical Science and Technology Project of Zhejiang Province(2022KY114)the National Natural Science Foundation of China(82204828).
文摘Aim:Scavenger receptor class B,type I(SR-BI)is an integral plasma membrane protein that has been reported to be overexpressed in various malignancies,such as renal cancer,breast cancer,and prostate cancer,and is an independent prognostic factor.However,the clinical value and expression of SR-BI in GC are unknown.Our research aimed to explore the role of SR-BI in combination with immune markers as a diagnostic and prognostic marker for gastric cancer(GC).Methods:GC tissues,paracancerous tissues,and clinicopathological data of 149 patients were collected.The expression level of SR-BI,Tumor-infiltrating lymphocytes(TILs),and PD-L1 were evaluated by immunohistochemistry(IHC).The associations of the SR-BI staining intensity with clinicopathological features and immune markers were determined by the chi-square test.Univariate and multivariate COX regression analyses were used to evaluate independent prognostic factors.Kaplan–Meier analyses were performed to plot the survival curve.Results:Our results indicated that SR-BI was expressed at higher levels in tumor tissues than in adjacent paracancerous tissues(p<0.001),and patients with high levels of SR-BI expression had a worse prognosis.Univariate and multivariate analyses revealed that high SR-BI expression was an independent factor for poor prognosis.The chi-square test determined that the expression of SR-BI was negatively correlated with CD4+T cells and CD8+T cells(CD4+T cells,p=0.013;CD8+T cells,p=0.021),and positively correlated with PD-L1(p=0.022).Finally,survival analysis revealed that CD4+T cells were associated with the prognosis of GC patients(p=0.019),and the combined survival analysis of SR-BI and CD4+T cells was also statistically significant(p=0.030).Conclusion:SR-BI is highly expressed in GC tissue and associated with poor prognosis.Moreover,SR-BI can also regulate the GC tumor immune microenvironment.
基金supported by the National Natural Science Foundation of China (Nos.31571500,31771623 and 31771628)the National Key Basic Research Program of China (2015CB942802)+1 种基金the Fundamental Research Funds for the Central Universities (XDJK2017A015)the Guangdong Natural Science Fund for Distinguished Young Scholars (2017A030306024)
文摘Zebrafish hematopoietic stem and progenitor cells（HSPCs） originate from the hemogenic endothelium of the ventral wall of the dorsal aorta（DA） through the endothelial-to-hematopoietic transition（EHT） from approximately 30 to 60 hours post fertilization（hpf）. However, whether other artery sites can generate HSPCs de novo remains unclear. In this study, using live imaging and lineage tracing, we found that the caudal dorsal artery（CDA） in the caudal hematopoietic tissue directly gave rise to HSPCs through EHT.This process initiated from approximately 60 hpf and terminated at approximately 156 hpf. Compared with that in the DA, fewer EHT events were observed in the CDA. The EHT events in the DA and CDA were similarly regulated by Runx1 but differentially influenced by blood flow（i.e., the EHT frequency in CDA was affected to a lesser extent when circulation was compromised in the tnnt2a～（-/-）mutant）. Therefore,the whole artery, including both DA and CDA, was endowed with the ability to produce HSPCs during a much longer time period. Coincidently, the lineage tracing results indicated that adult hematopoietic cells originated from the embryonic endothelium, and those produced later preferentially colonized the adult thymus. Collectively, our study revealed that the CDA serves as an additional source of hematopoiesis, and it shows similar but not identical properties with the DA.
