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RUNX2 和 LAMC2:通过对胰腺腺癌组织的综合数据挖掘鉴定出有前途的胰腺癌生物标志物。

RUNX2 and LAMC2: promising pancreatic cancer biomarkers identified by an integrative data mining of pancreatic adenocarcinoma tissues.

机构信息

Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.

出版信息

Aging (Albany NY). 2021 Oct 4;13(19):22963-22984. doi: 10.18632/aging.203589.

DOI:10.18632/aging.203589
PMID:34606473
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8544338/
Abstract

Pancreatic carcinoma (PC) is a severe disease associated with high mortality. Although strategies for cancer therapy have made great progress, outcomes of pancreatic carcinoma patients remain extremely poor. Therefore, it is urgent to find novel biomarkers and therapeutic targets. To identify biomarkers for early diagnosis and therapy, three mRNA microarray datasets and two miRNA datasets were selected, and combinative analysis was performed by GEO2R. Functional and pathway enrichment analysis were performed using DAVID database. MiRTarBase, miRWalk and Diana Tools were used to get key genes. TCGA, HPA and western blotting were used to verify diagnostic and prognostic value of key genes. By integrating mRNA and miRNA expression profiles, we identified 114 differentially expressed genes and 114 differentially expressed miRNAs, respectively. Then, three overlapping key genes, RUNX2, LAMC2 and FBXO32, were found. Their protein levels in pancreatic tissue from PC patients and normal people were analyzed by immunohistochemical staining and western blotting. RUNX2 showed a potential property to identify PC. Aberrant over-expression of LAMC2 was associated with poor prognosis of PC patients, tumor status and subtypes. In summary, our current study identified that RUNX2 and LAMC2 may be promising targets for early diagnosis and therapy of PC patients.

摘要

胰腺癌(PC)是一种死亡率很高的严重疾病。尽管癌症治疗策略已经取得了很大进展,但胰腺癌患者的预后仍然非常差。因此,迫切需要寻找新的生物标志物和治疗靶点。为了鉴定用于早期诊断和治疗的生物标志物,选择了三个 mRNA 微阵列数据集和两个 miRNA 数据集,并通过 GEO2R 进行了组合分析。使用 DAVID 数据库进行了功能和通路富集分析。使用 MiRTarBase、miRWalk 和 Diana Tools 获得了关键基因。使用 TCGA、HPA 和 Western blotting 验证了关键基因的诊断和预后价值。通过整合 mRNA 和 miRNA 表达谱,我们分别鉴定出 114 个差异表达基因和 114 个差异表达 miRNA。然后,发现了三个重叠的关键基因,RUNX2、LAMC2 和 FBXO32。通过免疫组织化学染色和 Western blotting 分析了来自 PC 患者和正常人胰腺组织中的这些蛋白的水平。RUNX2 显示出了一种潜在的识别 PC 的特性。LAMC2 的异常过表达与 PC 患者的不良预后、肿瘤状态和亚型有关。总之,我们的研究表明,RUNX2 和 LAMC2 可能是 PC 患者早期诊断和治疗的有前途的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3efa/8544338/603b94549429/aging-13-203589-g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3efa/8544338/a5ea264124e2/aging-13-203589-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3efa/8544338/603b94549429/aging-13-203589-g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3efa/8544338/032f0a363566/aging-13-203589-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3efa/8544338/8f3e6fa0a670/aging-13-203589-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3efa/8544338/f922e963315a/aging-13-203589-g007.jpg
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