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| 1 | Hypoxic microenvironment induced spatial transcriptome changes in pancreatic cancer显示文摘Objective: Hypoxia is a significant feature of solid tumors, including pancreatic ductal adenocarcinoma(PDAC). It is associated with tumor invasion, metastasis, and drug resistance. However, the spatial distribution of hypoxia-related heterogeneity in PDAC remains unclear.Methods: Spatial transcriptomics(STs), a new technique, was used to investigate the ST features of engrafted human PDAC in the ischemic hind limbs of nude mice. Transcriptomes from ST spots in the hypoxic tumor and the control were clustered using differentially-expressed genes. These data were compared to determine the spatial organization of hypoxia-induced heterogeneity in PDAC. Clinical relevance was validated using the Tumor Cancer Genome Atlas and KM-plotter databases. The CMAP website was used to identify molecules that may serve as therapeutic targets for PDAC.Results: ST showed that the tumor cell subgroups decreased to 7 subgroups in the hypoxia group, compared to 9 subgroups in the control group. Different subgroups showed positional characteristics and different gene signatures. Subgroup 6 located at the invasive front showed a higher proliferative ability under hypoxia. Subgroup 6 had active functions including cell proliferation, invasion, and response to stress. Expressions of hypoxia-related genes, LDHA, TPI1, and ENO1, induced changes. CMAP analysis indicated that ADZ-6482, a PI3 K inhibitor, was targeted by the invasive subgroup in hypoxic tumors.Conclusions: This study is the first to describe hypoxic microenvironment-induced spatial transcriptome changes in PDAC, and to identify potential treatment targets for PDAC. These data will provide the basis for further investigations of the prognoses and treatments of hypoxic tumors. | Huizhi Sun Danfang Zhang Chongbiao Huang Yuhong Guo Zhao Yang Nan Yao Xueyi Dong Runfen Cheng Nan Zhao Jie Meng Baocun Sun Jihui Hao | 2021 | Cancer Biology & Medicine2021，18，2： | 2 |
| 2 | Identification of hub genes and their novel diagnostic and prognostic significance in pancreatic adenocarcinoma显示文摘Objective:The main reasons for the poor prognoses of pancreatic adenocarcinoma(PA)patients are rapid early-stage progression,advanced stage metastasis,and chemotherapy resistance.Identification of novel diagnostic and prognostic biomarkers of PA is therefore urgently needed.Methods:Three mRNA microarray datasets were obtained from the Gene Expression Omnibus database to select differentially expressed genes(DEGs).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses for hub genes were performed using DAVID.Correlations between expression levels of hub genes and cancer-infiltrating immune cells were investigated by TIMER.Cox proportional hazard regression analyses were also performed.Serum hub genes were screened using the HPA platform and verified for diagnostic value using ELISAs.Results:We identified 59 hub genes among 752 DEGs.GO analysis indicated that these 59 hub genes were mainly involved in the defense response to viruses and the type I interferon signaling pathway.We also discovered that RSAD2 and SMC4 were associated with immune cell infiltration in the PA microenvironment.Additionally,DLGAP5 mRNA might be used as an independent risk factor for the prognoses of PA patients.Furthermore,the protein encoded by ISG15,which exists in peripheral blood,was validated as a potential diagnostic biomarker that distinguished PA patients from healthy controls(area under the curve:0.902,95%confidence interval:0.819–0.961).Conclusions:Our study suggested that RSAD2 and SMC4 were associated with immune cell infiltration in the PA microenvironment,while DLGAP5 mRNA expression might be an independent risk factor for the survival prognoses of PA patients.Moreover,ELISAs indicated that serum ISG15 could be a potential novel diagnostic biomarker for PA. | Duo Zuo Yongzi Chen Xinwei Zhang Zhuozhi Wang Wenna Jiang Fan Tang Runfen Cheng Yi Sun Lu Sun Li Ren Rui Liu | 2022 | Cancer Biology & Medicine2022，19，7： | 1 |
| 3 | ENO1 expression and Erk phosphorylation in PDAC and their effects on tumor cell apoptosis in a hypoxic microenvironment显示文摘Objective: Hypoxia is an important feature of pancreatic ductal adenocarcinoma(PDAC). Previously, we found that hypoxia promotes ENO1 expression and PDAC invasion. However, the underlying molecular mechanism was remains unclear.Methods: The relationship between ENO1 expression and clinicopathological characteristics was analyzed in 84 patients with PADC. The effects of CoCl2-induced hypoxia and ENO1 downregulation on the apoptosis, invasion, and proliferation of PDAC cells were evaluated in vitro and in vivo. Hypoxia-and ENO1-induced gene expression was analyzed by transcriptomic sequencing.Results: The prognosis of PDAC with high ENO1 expression was poor(P < 0.05). High ENO1 expression was closely associated with histological differentiation and tumor invasion in 84 PDAC cases(P < 0.05). Hypoxia increased ENO1 expression in PDAC and promoted its migration and invasion. Apoptotic cells and the apoptosis marker caspase-3 in the CoCl_(2)-treated ENO1-sh group were significantly elevated(P < 0.05). Transcriptomic sequencing indicated that CoCl_(2)-induced PDAC cells initiated MAPK signaling. Under hypoxic conditions, PDAC cells upregulated ENO1 expression, thereby accelerating ERK phosphorylation and inhibiting apoptosis(P < 0.05). Consistent results were also observed in a PDAC-bearing mouse hindlimb ischemia model.Conclusions: Hypoxia-induced ENO1 expression promotes ERK phosphorylation and inhibits apoptosis, thus leading to PDAC survival and invasion. These results suggest that ENO1 is a potential therapeutic target for PDAC. | Huizhi Sun Jing Mo Runfen Cheng Fan Li Yue Li Yuhong Guo Yanlei Li Yanhui Zhang Xiaoyu Bai Yalei Wang Xueyi Dong Danfang Zhang Jihui Hao | 2022 | Cancer Biology & Medicine2022，19，11： | 0 |
| 4 | Therapeutic Effect of Bone Marrow Mesenchymal Stem Cells on Rat Bladder Cancer显示文摘Objective:To analyze the effect of bone marrow mesenchymal stem cell therapy on rats with bladder cancer and provide a feasible direction for the treatment of human bladder cancer.Methods:An animal model was constructed,and Model 1 was used as an example.Two groups of rats were injected with anti-upconversion nanoparticles(UCNPs)(experimental group)and 0.9%normal saline(control group),respectively.In vivo imaging was performed to determine the accuracy of the anti-UCNPs method.Results:There were 15 rats in the experimental group with obvious bladder swelling.Among them,11 rats had cauliflower-like and partially brown bladder tumors,whereas the other four rats had hard,nodular-like protrusions,with indistinct borders and adhesions to the anterior wall of the rectum.Small papillary masses were observed in two rats,local mucosal thickening without tumor formation was observed in two rats,and bladder stones were observed in six rats.The bladder specimens of 15 rats in the control group were pink and shiny,without any tumors.Fourteen rats in the experimental group and 12 rats in the control group had bladder cancer lesions,accounting for 93.33%and 80%,respectively.The detection accuracy of the experimental group was significantly better than that of the control group.Conclusion:Multimodal nanoprobes targeting bladder cancer stem cells in vivo were used to image the orthotopic tumor and lymph node metastasis models of animals by anti-UCNPs imaging to observe the distribution,migration,and differentiation process of bladder cancer stem cells in model mice.It is clear that rare earth upconversion luminescent nanomaterials,modified by BCMab1 and CD44 monoclonal antibodies,can be used as probes for the detection of bladder cancer,the tracking of lymph node metastasis in bladder cancer,and the comprehensive evaluation of the overall efficacy of nanoprobe-targeted therapy for bladder cancer stem cells. | Jinmei Li Runfen Cheng Bingjuan Zhou Zhiqiang Zhang Qiongli Zhai Jinku Zhang | 2022 | Proceedings of Anticancer Research2022，6，6： | 0 |
| 5 | Research Progress of Prostate Stem Cell Antigen in Bladder Cancer Treatment显示文摘In order to study the application effect of prostate stem cell antigen in the treatment of bladder cancer,several literatures have been reviewed in this paper,including the predisposition factors of bladder cancer,clinical treatment methods,progress of prostate stem cell antigen,and nanomaterial probe.This paper presents a feasible method of using luminescent nanomaterials(anti-UCNPs)as biological probes. | Jinmei Li Runfen Cheng Bingjuan Zhou Zhiqiang Zhang Qiongli Zhai Jinku Zhang | 2022 | Proceedings of Anticancer Research2022，6，5： | 0 |
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