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Identifying and validating MMP family members(MMP2,MMP9,MMP12,and MMP16)as therapeutic targets and biomarkers in kidney renal clear cell carcinoma(kirc)

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Oncology Research 2024年第4期32卷 737-752页

作者： KUNLUN LI DANDAN LI BARBOD HAFEZ MOUNIR M.SALEM BEKHIT YOUSEF A.BIN JARDAN FARS KAED ALANAZI EHAB I.TAHA SAYED H.AUDA FAIQAH RAMZAN MUHAMMAD JAMIL The Second Affiliated Hospital of Harbin Medical University Harbin Medical UniversityHarbinChina Department of Pharmaceutical Engineering Jiangsu Ocean UniversityLianyungangChina Department of Biological Engineering University of SalfordSalfordUK Department of Pharmaceutics College of PharmacyKing Saud UniversityRiyadhSaudi Arabia Department of Animal and Poultry Production Faculty of Veterinary and Animal SciencesGomal UniversityDera Ismail KhanPakistan Department of Arid Zone Research PARC instituteDera Ismail KhanPakistan

Kidney Renal Clear Cell Carcinoma(kirc)is a malignant tumor that carries a substantial risk of morbidity and *** MMP family assumes a crucial role in tumor invasion and *** study aimed to uncover the mechanistic relevance of the MMP gene family as a therapeutic target and diagnostic biomarker in Kidney Renal Clear Cell Carcinoma(kirc)through a comprehensive approach encompassing both computational and molecular ***,Cytoscape,UALCAN,GEPIA,OncoDB,HPA,cBioPortal,GSEA,TIMER,ENCORI,DrugBank,targeted bisulfite sequencing(bisulfite-seq),conventional PCR,Sanger sequencing,and RT-qPCR based analyses were used in the present study to analyze MMP gene family members to accurately determine a few hub genes that can be utilized as both therapeutic targets and diagnostic biomarkers for *** performing STRING and Cytohubba analyses of the 24 MMP gene family members,MMP2(matrix metallopeptidase 2),MMP9(matrix metallopeptidase 9),MMP12(matrix metallopeptidase 12),and MMP16(matrix metallopeptidase 16)genes were denoted as hub genes having highest degree *** analyzing MMP2,MMP9,MMP12,and MMP16 via various TCGA databases and RT-qPCR technique across clinical samples and kirc cell lines,interestingly,all these hub genes were found significantly overexpressed at mRNA and protein levels in kirc samples relative to *** notable effect of the up-regulated MMP2,MMP9,MMP12,and MMP16 was also documented on the overall survival(OS)of the kirc ***,targeted bisulfite-sequencing(bisulfite-seq)analysis revealed that promoter hypomethylation pattern was associated with up-regulation of hub genes(MMP2,MMP9,MMP12,and MMP16).In addition to this,hub genes were involved in various diverse oncogenic *** MMP gene family members(MMP2,MMP9,MMP12,and MMP16)may serve as therapeutic targets and prognostic biomarkers in kirc.

关键词： kirc MMP gene family Chemotherapy Overall survival

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Deciphering key genes involved in cisplatin resistance in kidney renal clear cell carcinoma through a combined in silico and in vitro approach

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肿瘤学研究(英文) 2023年第6期31卷 899-916页

作者： MUNEEBA MALIK MAMOONA MAQBOOL TOOBA NISAR TAZEEM AKHTER JAVED AHMED UJAN ALANOOD SALGARNI FAKHRIA AAL JOUFI SULTAN SHAFI KALANAZI MOHAMMAD HADI ALMOTARED MOUNIR MSALEM BEKHIT MUHAMMAD JAMIL Services Hospital LahorePakistan Sabzazar Medical Center LahorePakistan BHU Pourmiana AttockPakistan Public Health Department University of Health SciencesLahorePakistan Department of Zoology Shah Abdul Latif UniversityKhairpurPakistan Department of Animal Sciences University of FloridaGainesvilleUSA Pharmacology and Toxicology Department College of Pharmacy Umm Al-Qura UniversityMakkahSaudi Arabia Department of Pharmacology College of PharmacyJouf UniversityAljoufSaudi Arabia Regional Laboratory and Blood Bank(Total Laboratory Automation) RiyadhSaudi Arabia Health Affairs in Najran New Najran General HospitalNajranSaudi Arabia Department of Pharmaceutics College of PharmacyKing Saud UniversityRiyadhSaudi Arabia PARC Arid Zone Research Center Dera Ismail KhanPakistan

The low survival rate of Kidney renal clear cell carcinoma(kirc)patients is largely attributed to cisplatin *** than focusing solely on individual proteins,exploring protein-protein interactions could offer greater insight into drug *** this end,a series of in silico and in vitro experiments were conducted to identify hub genes in the intricate network of cisplatin resistance-related genes in kirc *** genes involved in cisplatin resistance across kirc were retrieved from the National Center for Biotechnology Information(NCBI)database using search terms as“Kidney renal clear cell carcinoma”and“Cisplatin resistance”.The genes retrieved were analyzed for hub gene identification using the STRING database and Cytoscape *** and promoter methylation profiling of the hub genes was done using UALCAN,GEPIA,OncoDB,and HPA ***,survival,functional enrichment,immune cell infiltration,and drug prediction analyses of the hub genes were performed using the cBioPortal,GEPIA,GSEA,TIMER,and DrugBank ***,expression and methylation levels of the hub genes were validated on two cisplatin-resistant RCC cell lines(786-O and A-498)and a normal renal tubular epithelial cell line(HK-2)using two high throughput techniques,including targeted bisulfite sequencing(bisulfite-seq)and RT-qPCR.A total of 124 genes were identified as being associated with cisplatin resistance in *** of these genes,MCL1,IGF1R,CCND1,and PTEN were identified as hub genes and were found to have significant(pkirc ***,an aberrant promoter methylation pattern was found to be associated with the dysregulation of the hub *** addition to this,hub genes were also linked with different cisplatin resistance-causing ***,hub genes can be targeted with Alvocidib,Estradiol,Tretinoin,Capsaicin,Dronabinol,Metribolone,Calcitriol

关键词： kirc Cisplatin resistance Chemotherapy Overall survival

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预测肾透明细胞癌预后的新型鞘磷脂信号通路相关风险评估模型的建立

预测肾透明细胞癌预后的新型鞘磷脂信号通路相关风险评估模型的建...

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作者：孙永浩大连医科大学

学位级别：硕士

本研究旨在探讨鞘脂相关基因在肾透明细胞癌(kirc)中发挥作用的潜在机制,并构建新的预后相关风险模型。我们使用了各种生物信息学方法和数据库来完成我们的探索。基于TCGA数据库,我们使用多个基于R的扩展包进行数据转换、处理和统计分... 详细信息

本研究旨在探讨鞘脂相关基因在肾透明细胞癌(kirc)中发挥作用的潜在机制,并构建新的预后相关风险模型。我们使用了各种生物信息学方法和数据库来完成我们的探索。基于TCGA数据库,我们使用多个基于R的扩展包进行数据转换、处理和统计分析。首先,通过分析不同类型癌症中29个鞘脂相关基因的CNV、SNV和m RNA表达,我们发现绝大多数在kirc中具有保护性。随后,我们使用鞘脂相关基因对kirc患者进行了聚类分析,并成功地将其分为以下三个具有显著预后差异的聚类:聚类1、聚类2和聚类3。我们对转录因子活性、药物敏感性、免疫细胞浸润和经典癌基因进行了差异分析,以阐明鞘磷脂相关基因在癌症尤其是kirc中的独特作用,并为临床治疗提供参考。在分析kirc中鞘脂相关基因的风险率后,我们使用LASSO回归分析成功地建立了由7个基因组成的风险模型,包括SPHK1、CERS5、PLPP1、SGMS1、SGMS 2、SERINC1和KDSR。先前的研究表明,这些基因在鞘脂代谢中起着重要的生物学作用。ROC曲线分析结果表明,风险模型提供了良好的预测精度。基于该风险模型,我们成功地将kirc患者分为具有显著预后差异的高风险组和低风险组。此外,我们结合临床病理数据进行了相关性分析,发现风险模型与患者的M、T、分期、等级和fustat之间存在显著相关性。最后,我们开发了一个诺模图,预测了kirc患者的5年、7年和10年生存率。我们构建的模型具有很强的预测能力。总之,我们认为这项研究为今后研究kirc中鞘脂相关基因提供了宝贵的数据和线索。

关键词： kirc 鞘脂基因预测模型

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MiR-144-3p调控E2F8对肾透明细胞癌增殖、凋亡的影响

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实用临床医学（江西） 2023年第3期24卷 18-25页

作者：田捷余黄琴周敏郭龙刘飞南昌大学第二附属医院泌尿外科南昌330006 九江市第一人民医院耳鼻喉科江西九江332000

目的研究miR-144-3p对肾透明细胞癌(kirc)增殖、凋亡的影响并探究其分子机制.方法检测肾小管上皮细胞HK2和kirc细胞系786-O、ACHN、OS-RC-2中miR-144-3p、E2F8 mRNA和E2F8蛋白的表达差异;检测kirc组织和癌旁组织中miR-144-3p和E2F8 mRN... 详细信息

目的研究miR-144-3p对肾透明细胞癌(kirc)增殖、凋亡的影响并探究其分子机制.方法检测肾小管上皮细胞HK2和kirc细胞系786-O、ACHN、OS-RC-2中miR-144-3p、E2F8 mRNA和E2F8蛋白的表达差异;检测kirc组织和癌旁组织中miR-144-3p和E2F8 mRNA的表达差异.采用荧光素酶报告实验验证E2F8 mRNA和miR-144-3p的互作关系.分别在786-O细胞中过表达miR-144-3p和沉默E2F8,采用WB检测增殖、凋亡相关蛋白的表达;同时在786-O细胞中过表达miR-144-3p和过表达E2F8,并检测增殖、凋亡相关蛋白的表达;分别采用CCK8法和流式细胞术检测上述转染细胞的增殖和凋亡.结果与HK2细胞相比,kirc细胞系786-O、ACHN、OS-RC-2中miR-144-3p表达水平较低(Pkirc组织中miR-144-3p表达水平较低(Pkirc肿瘤细胞786-O的增殖和促进其细胞凋亡.

关键词： miR-144-3p E2F8 kirc 增殖凋亡

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DLGAP5作为肾透明细胞癌的诊断标志物及其与CD8+T细胞的相关性

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医学信息 2023年第7期36卷 1-8页

作者：李坤韩娜凡志祥陈泓润靳爽张中冕郑州大学第二附属医院肿瘤科

目的探讨Discs大同源物关联蛋白5(DLGAP5)表达在肾透明细胞癌(kirc)中的作用。方法基于癌症基因组图谱(TCGA)分析kirc中DLGAP5的表达情况与临床参数之间的相关性。应用比例风险(Cox)回归模型和Kaplan-Meier(K-M)分析评估了DLGAP5在KIR... 详细信息

目的探讨Discs大同源物关联蛋白5(DLGAP5)表达在肾透明细胞癌(kirc)中的作用。方法基于癌症基因组图谱(TCGA)分析kirc中DLGAP5的表达情况与临床参数之间的相关性。应用比例风险(Cox)回归模型和Kaplan-Meier(K-M)分析评估了DLGAP5在kirc患者中的预后价值。CIBERSORT分析DLGAP5和CD8+T细胞之间的相关性，基因集富集分析(GSEA)方法筛选和DLGAP5表达相关的生物学途径。结果与正常肾脏组织比较，kirc中DLGAP5的表达呈显著上调。其高表达情况与肿瘤组织的分化程度、病理分期、复发和死亡均显著相关。K-M分析结果表明，DLGAP5高表达与kirc患者的不良总生存期(OS)和无进展生存期(PFS)相关，且DLGAP5是OS和PFS的独立预后因子。免疫微环境分析表明，DLGAP5的表达量与多种肿瘤免疫细胞相关，尤其是CD8+T细胞。DLGAP5表达在“细胞周期”“泛素介导的蛋白水解”“蛋白酶体通路”和“T细胞受体信号通路”上显著富集。药敏分析结果显示，高危组患者对阿昔替尼、舒尼替尼更敏感。结论 DLGAP5是kirc的一种潜在生物标志物，与kirc的诊断与预后显著相关，这将为临床的诊断与治疗提供新的研究方向。

关键词： DLGAP5 CD8+T细胞 kirc TCGA数据库预后

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A novel prognosis signature based on two cuprotosis-related genes for kidney renal clear cell carcinoma

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Medical Data Mining 2022年第4期5卷 62-73页

作者： Xing-Yun Liu Jing-Duo Zhao Ze-Rui Yang Guo-Tao Tang Yu-Sheng Zhou The Affiliated Nanhua Hospital Hengyang Medical SchoolUniversity of South ChinaHengyangChina Institute of Pharmacy and Pharmacology Hunan Province Cooperative Innovation Center for Molecular Target New Drug StudyUniversity of South ChinaHengyangChina Key Specialty of Clinical Pharmacy the First Affiliated Hospital of Guangdong Pharmaceutical UniversityGuangzhouChina

Background:Cuprotosis is a newly discovered Copper-dependence form of cell ***-related genes(CRGs)regulating mitochondrial metabolism and protein lipoylation suggest the critical roles cuprotosis for in ***,the prognostic value of CRGs in the highly immunogenic cancer type,kidney renal clear cell carcinoma(kirc)needs to be further ***,we aim to identify novel prognostic genes and construct a CRGs prognostic signature for ***:We downloaded the mRNA sequencing data from the Cancer Genome Atlas,differentially expressed CRGs were screened out and their bio-function was *** we used Cox regression analysis to establish a prediction model of ***,a prognostic scoring model based on the regression coefficients of the screened out CRGs and their corresponding mRNA expressions were constructed and ***:Seven differentially expressed CRGs were screened.A two-gene model was built to separate samples into high-risk and low-risk *** survival was lower in the high-risk group than in the low-risk group(pkirc ***,risk score has a very significant effect on the infiltration of immune cells and the expression of immune ***:To conclude,we constructed a novel prognostic signature based on *** cuprotosis may represent a promising approach for the treatment of kirc.

关键词： cuprotosis kirc prognostic signature cuprotosis-related genes

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