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Identification of hub genes and their novel diagnostic and prognostic significance in pancreatic adenocarcinoma

Cancer Biology & Medicine 2022年第7期19卷 1029-1046页

作者： Duo Zuo Yongzi Chen Xinwei Zhang Zhuozhi Wang Wenna Jiang Fan Tang runfen cheng Yi Sun Lu Sun Li Ren Rui Liu Department of Clinical Laboratory Department of Tumor Cell Biology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China School of Biomedical Engineering Tianjin Medical UniversityTianjin 300070China Department of Pathology Tianjin Huanhu HospitalTianjin 300350China Department of Pathology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China School of Pharmacy Tianjin Medical UniversityTianjin 300070China Department of Gastrointestinal Medical Oncology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China

Objective:The main reasons for the poor prognoses of pancreatic adenocarcinoma(PA)patients are rapid early-stage progression,advanced stage metastasis,and chemotherapy *** of novel diagnostic and prognostic biomarkers of PA is therefore urgently ***: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 *** between expression levels of hub genes and cancer-infiltrating immune cells were investigated by *** proportional hazard regression analyses were also *** hub genes were screened using the HPA platform and verified for diagnostic value using ***:We identified 59 hub genes among 752 *** analysis indicated that these 59 hub genes were mainly involved in the defense response to viruses and the type I interferon signaling *** also discovered that RSAD2 and SMC4 were associated with immune cell infiltration in the PA ***,DLGAP5 mRNA might be used as an independent risk factor for the prognoses of PA ***,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 ***,ELISAs indicated that serum ISG15 could be a potential novel diagnostic biomarker for PA.

关键词： RSAD2 SMC4 DLGAP5 ISG15 pancreatic adenocarcinoma

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ENO1 expression and Erk phosphorylation in PDAC and their effects on tumor cell apoptosis in a hypoxic microenvironment

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Cancer Biology & Medicine 2022年第11期19卷 1598-1616页

作者： 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 Tianjin Medical University Cancer Institute&Hospital National Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin's Clinical Research Center for CancerTianjin 300060China Department of Pathology Tianjin Medical UniversityTianjin300070China

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 ***: 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 ***: 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 ***: 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.

关键词： Pancreatic cancer hypoxia ENOl apoptosis Erk phosphorylation

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Research Progress of Prostate Stem Cell Antigen in Bladder Cancer Treatment

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Proceedings of Anticancer Research 2022年第5期6卷 51-57页

作者： Jinmei Li runfen cheng Bingjuan Zhou Zhiqiang Zhang Qiongli Zhai Jinku Zhang Department of Pathology Baoding First Central HospitalBaoding 071000Hebei ProvinceChina The Key Laboratory of Molecular Pathology and Early Diagnosis of Tumor in Hebei Province Baoding 071000Hebei ProvinceChina Department of Pathology Cancer Hospital of Tianjin Medical UniversityNational Clinical Medical Research Center of CancerTianjin Key Laboratory of Cancer Prevention and TreatmentTianjin Clinical Medical Research Center of Malignant CancerTianjin 300060China Department of Thoracic Surgery Baoding First Central HospitalBaoding 071000Hebei ProvinceChina

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 *** paper presents a feasible method of using luminescent nanomaterials(anti-UCNPs)as biological probes.

关键词： Bladder cancer Prostate stem cells Nanoprobes

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Hypoxic microenvironment induced spatial transcriptome changes in pancreatic cancer

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Cancer Biology & Medicine 2021年第2期18卷 616-630页

作者： Huizhi Sun Danfang Zhang Chongbiao Huang Yuhong Guo Zhao Yang Nan Yao Xueyi Dong runfen cheng Nan Zhao Jie Meng Baocun Sun Jihui Hao Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Department of Pathology School of Basic Medical ScienceTianjin Medical UniversityTianjin 300070China

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 ***: 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 ***: 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 ***: 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.

关键词： Pancreatic cancer hypoxia spatial transcriptomic

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Therapeutic Effect of Bone Marrow Mesenchymal Stem Cells on Rat Bladder Cancer

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Proceedings of Anticancer Research 2022年第6期6卷 15-20页

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 ***:An animal model was constructed,and Model 1 was used as an *** groups of rats were injected with anti-upconversion nanoparticles(UCNPs)(experimental group)and 0.9%normal saline(control group),*** vivo imaging was performed to determine the accuracy of the anti-UCNPs ***:There were 15 rats in the experimental group with obvious bladder *** 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 *** 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 *** bladder specimens of 15 rats in the control group were pink and shiny,without any *** rats in the experimental group and 12 rats in the control group had bladder cancer lesions,accounting for 93.33%and 80%,*** detection accuracy of the experimental group was significantly better than that of the control ***: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 *** 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.

关键词： Bone marrow Stem cells Bladder cancer

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卵巢癌中MPC2的表达及其生物学功能

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中国肿瘤临床 2018年第15期45卷 774-779页

作者：程润芬孙保存杨海翠杨烨天津医科大学肿瘤医院病理科国家肿瘤临床医学研究中心天津市肿瘤防治重点实验室天津市恶性肿瘤临床医学研究中心天津市300060

目的:检测线粒体丙酮酸载体蛋白2(mitochondrial pyruvate carrier 2,MPC2)在卵巢癌组织中的表达,并分析MPC2在卵巢癌进展过程中可能的生物学功能。方法:利用http://***/analysis/数据库分析卵巢癌组织中MPC2 mRNA表达水平与患者生存预... 详细信息

目的:检测线粒体丙酮酸载体蛋白2(mitochondrial pyruvate carrier 2,MPC2)在卵巢癌组织中的表达,并分析MPC2在卵巢癌进展过程中可能的生物学功能。方法:利用http://***/analysis/数据库分析卵巢癌组织中MPC2 mRNA表达水平与患者生存预后的关系,收集天津医科大学肿瘤医院2009年至2011年137例卵巢癌组织,采用免疫组织化学方法测定MPC2在卵巢癌组织中的蛋白表达水平,采用SPSS 16.0软件统计分析MPC2蛋白表达水平与卵巢癌患者年龄、临床分期、病理分级、腹水、有无远处转移等临床病理指标之间的关系,分析MPC2蛋白表达水平与患者生存预后的关系。构建MPC2过表达细胞,观察MPC2对细胞生物学功能的影响作用。结果:MPC2 mRNA与卵巢癌患者的总生存期(ovall survival,OS)和无进展生存期(progression free survival,PFS)均存在显著的相关性,MPC2 mRNA低表达的患者预后较差。在卵巢癌组织中MPC2的蛋白表达水平与临床分期、腹水和远处转移有关(P<0.05),MPC2低表达的患者临床分期较高、有腹水产生、出现远处转移,MPC2表达与患者生存预后显著相关,MPC2低表达的患者预后较差(P<0.01)。MPC2过表达可以显著抑制细胞的增殖和迁移能力。结论:MPC2与卵巢癌的恶性进展密切相关,MPC2低表达的卵巢癌患者预后较差,且MPC2可显著抑制卵巢癌细胞的增殖能力,提示MPC2有望成为卵巢癌治疗的潜在靶点。

关键词：线粒体丙酮酸载体蛋白2 卵巢癌临床病理预后

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PD-L1在混合型肝癌中的表达及临床意义

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中华肝胆外科杂志 2023年第11期29卷 820-825页

作者：孙博巩文辰韩智强齐丽莎程润芬贺钰超董秋萍朱康伟韩濡郁耿长宇宋天强陈璐天津医科大学肿瘤医院、国家恶性肿瘤临床医学研究中心、天津市恶性肿瘤临床医学研究中心、天津市肿瘤防治重点实验室天津300060

目的检测混合型肝癌组织中程序性死亡蛋白配体1(PD-L1)的表达水平,探讨PD-L1表达水平与混合型肝癌患者临床特征和预后的关系。方法回顾性分析2011年1月至2019年12月天津医科大学肿瘤医院收治并行手术治疗的75例混合型肝癌患者的临床资料... 详细信息

目的检测混合型肝癌组织中程序性死亡蛋白配体1(PD-L1)的表达水平,探讨PD-L1表达水平与混合型肝癌患者临床特征和预后的关系。方法回顾性分析2011年1月至2019年12月天津医科大学肿瘤医院收治并行手术治疗的75例混合型肝癌患者的临床资料,其中男性61例,女性14例,年龄范围36~77岁,中位年龄55岁。应用免疫组化法检测75例癌组织中PD-L1表达水平,并分为PD-L1阴性组(n=66)和阳性组(n=9),并分析其与患者临床病理学特征及预后的关系。结果在低分化混合型肝癌的癌组织中PD-L1表达阳性比例为21.1%(8/38),高于中高分化癌组织的2.7%(1/37),差异有统计学意义(χ^(2)=4.366,P=0.037)。PD-L1阳性患者的中位无复发生存期(DFS)、总生存期(OS)分别为12.3个月和15.1个月,低于PD-L1阴性患者的中位DFS 14.4个月和OS 23.3个月,但仅DFS差异具有统计学意义(χ^(2)=4.052,P=0.044)。在多因素分析中,仅有大血管侵犯(DFS:HR=1.965,95%CI:1.119~3.450,P=0.019;OS:HR=1.781,95%CI:1.022~3.105,P=0.042)和淋巴结转移(DFS:HR=2.451,95%CI:1.1033~5.814,P=0.042;OS:HR=2.652,95%CI:1.120~6.279,P=0.027)是影响患者DFS、OS的独立预后因素。结论PD-L1在低分化混合型肝癌中的阳性比例较中高分化癌高;大血管侵犯和淋巴结转移是影响混合性肝癌患者预后的独立因素。

关键词：肝肿瘤混合型肝癌程序性死亡蛋白配体1 临床病理学特征预后

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肺外炎性肌纤维母细胞瘤的影像学表现及病理对照分析

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中国肿瘤临床 2019年第21期46卷 1091-1096页

作者：曲方园程润芬刘颖黄金超叶兆祥天津医科大学肿瘤医院放射科国家肿瘤临床医学研究中心天津市肿瘤防治重点实验室天津市恶性肿瘤临床医学研究中心天津市300060 天津医科大学肿瘤医院病理科国家肿瘤临床医学研究中心天津市肿瘤防治重点实验室天津市恶性肿瘤临床医学研究中心天津市300060 天津医科大学肿瘤医院预防医学中心国家肿瘤临床医学研究中心天津市肿瘤防治重点实验室天津市恶性肿瘤临床医学研究中心天津市300060

目的:探讨肺外炎性肌纤维母细胞瘤(extrapulmonary inflammatory myofibroblastic tumor,EPIMT)的CT与MRI表现。方法:回顾性分析2011年1月至2019年8月天津医科大学肿瘤医院经手术或穿刺病理及免疫组织化学证实的30例EPIMT患者影像学资料... 详细信息

目的:探讨肺外炎性肌纤维母细胞瘤(extrapulmonary inflammatory myofibroblastic tumor,EPIMT)的CT与MRI表现。方法:回顾性分析2011年1月至2019年8月天津医科大学肿瘤医院经手术或穿刺病理及免疫组织化学证实的30例EPIMT患者影像学资料,总结病灶部位、大小、形态、边界、密度/信号、强化方式等影像表现特征。结果:30例EPIMT中,28例为单发病灶、2例为双发病灶。30例患者的32个肿瘤中,20个形态不规则、11个呈圆形或椭圆形、1个呈多结节融合状;病灶多边界不清,侵犯周围组织或与之黏连;8个其内可见囊变坏死,钙化及出血少见;多数病例CT增强检查后呈明显或中度强化,以渐进性持续强化为主,少数呈"慢进慢出"的强化方式;9例MRI增强检查后均表现为中度或明显延迟强化。免疫组织化学法结果显示,Ki-67增殖指数平均值<5%的例数约占50.0%,Vimentin、SMA及ALK阳性率分别为93.3%、86.7%及31.8%,S-100阴性率81.8%。结论:EPIMT的影像学表现为单发、边界不清伴絮状渗出、平扫呈均匀密度/信号,强化方式"渐进性持续强化"或"慢进慢出",瘤周出现淋巴结。对照分析病理总结病变的影像特征,旨在提高影像诊断准确性,并对分型有提示作用。

关键词：肺外炎性肌纤维母细胞瘤体层摄影术 X线计算机磁共振成像

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Dickkopf-1对结肠癌组织血管生成拟态形成的抑制作用及相关机制研究

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中国肿瘤临床 2015年第20期42卷 1007-1011页

作者：齐丽莎刘志勇宋汪昭程润芬孙保存天津医科大学肿瘤医院病理科国家肿瘤临床医学研究中心天津市肿瘤防治重点实验室天津市300060 天津医科大学病理教研室

目的:探讨结肠癌组织中Dickkopf-1(Dkk1)表达对血管生成拟态(vasculogenic mimicry,VM)的抑制作用及相关机制。方法:收集2002年1月至2004年12月间天津医科大学肿瘤医院收治的217例结肠癌患者资料,利用CD34-PAS对结肠癌组织进行双重染色... 详细信息

目的:探讨结肠癌组织中Dickkopf-1(Dkk1)表达对血管生成拟态(vasculogenic mimicry,VM)的抑制作用及相关机制。方法:收集2002年1月至2004年12月间天津医科大学肿瘤医院收治的217例结肠癌患者资料,利用CD34-PAS对结肠癌组织进行双重染色及免疫组化方法检测并分析VM与Dkk1表达的关系;利用体外三维培养(three dimensional culture,3D culture)观察Dkk1对人结肠癌HCT116细胞管状结构形成能力及血管内皮钙黏蛋白(VE-cadherin)表达的影响;建立裸鼠皮下移植瘤模型进一步明确Dkk1对肿瘤组织内VM形成的抑制作用。结果:存在VM的结肠癌组织中Dkk1表达较低(P<0.05);Dkk1过表达的HCT116细胞形成管状结构能力明显减弱,且VE-cadherin表达降低;Dkk1可抑制裸鼠移植瘤组织中HCT116细胞形成VM。结论:Dkk1过表达可抑制结肠癌中VM形成。

关键词： Dickkopf-1 血管生成拟态结肠癌三维培养

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消化系统神经内分泌肿瘤的临床病理特征与生存分析

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中国肿瘤临床 2018年第6期45卷 277-285页

作者：张靖宜王超孙琳程润芬赵帅孙保存孙燕天津医科大学肿瘤医院病理科国家肿瘤临床医学研究中心天津市肿瘤防治重点实验室天津市恶性肿瘤临床医学研究中心天津市300060

目的:探讨消化系统不同部位神经内分泌肿瘤(neuroendocrine neoplasms,NENs)的临床病理特征及预后因素。方法:收集天津医科大学肿瘤医院2011年3月至2015年12月收治的284例消化系统NENs,分析比较不同部位NENs临床病理特征的异同,并进行... 详细信息

目的:探讨消化系统不同部位神经内分泌肿瘤(neuroendocrine neoplasms,NENs)的临床病理特征及预后因素。方法:收集天津医科大学肿瘤医院2011年3月至2015年12月收治的284例消化系统NENs,分析比较不同部位NENs临床病理特征的异同,并进行生存分析。结果:本研究中,消化系统NENs以胰腺部位最多见,其次为结直肠、胃。在胰腺NENs中,以G1(51.8%)和G2(35.8%)型为主,WHO分类与淋巴结转移、周围器官侵犯、神经侵犯有关(均P40岁的患者更多;神经内分泌癌和混合性腺神经内分泌癌比例更高、淋巴结转移和远处转移的比例更高;进展期的患者更多(均P<0.05)。WHO分类和有无淋巴结转移与胃NENs的总生存期有关(均P<0.05)。结论:消化系统NENs是一组异质性肿瘤,不同部位的肿瘤具有不同的临床病理特征,并与欧美国家存在差异。仍需要大样本多中心研究来了解不同部位消化系统NENs的生物学行为及预后因素。

关键词：神经内分泌肿瘤胃肠胰预后

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