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KRT6A、KRT6B、PKP1和PKP3作为食管癌中的关键枢纽基因:一项生物信息学与实验相结合的研究

KRT6A, KRT6B, PKP1, and PKP3 as key hub genes in esophageal cancer: A combined bioinformatics and experimental study.

作者信息

Marhamati Shayan, Hamrahjoo Morvarid, Seyedkhan Zeinab, Bahmani Mahdi, Ziamajidi Nasrin, Khodadadi Iraj, Pouryani Mohadese, Abbasalipourkabir Roghayeh

机构信息

Department of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran.

出版信息

Biochem Biophys Rep. 2025 Jun 22;43:102095. doi: 10.1016/j.bbrep.2025.102095. eCollection 2025 Sep.

DOI:10.1016/j.bbrep.2025.102095
PMID:40612005
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12226072/
Abstract

Esophageal cancer (EC) is the eighth most common cancer in the world. Due to poor survival rates and severe side effects of current therapies, there is a need for a better understanding of the mechanisms and signaling pathways involved in EC. In this study, we downloaded the microarray datasets GSE157808 and GSE92396 from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified using R software and validated through the GEPIA and TIMER databases. CytoHubba was used to extract hub genes from the overlapping DEGs. The TIMER database was employed to assess correlations between gene expression and immune infiltration. Additionally, hub gene expression was analyzed in 20 pairs of EC tissue samples through RT-qPCR and Western blot. We evaluated clinicopathological correlations and diagnostic potential. We identified 83 overlapping DEGs across the datasets. Subsequently, based on the highest number of degrees in the hub gene network, the , and genes were selected for further experimental analysis. EC samples showed upregulated expression of these genes, consistent with our bioinformatic analysis and the GEPIA and TIMER databases. However, KRT6B protein levels were not significantly elevated. expression was associated with lymph node metastasis, while showed an inverse relationship with necrosis. Gene expression levels correlated with components of immune infiltration. ROC analysis indicated possible diagnostic value, while Kaplan-Meier plots showed no significant association with survival outcomes. Elevated expression of , , , and is associated with EC, indicating their potential as candidates for further investigation.

摘要

食管癌(EC)是全球第八大常见癌症。由于目前治疗方法的生存率低且副作用严重,因此需要更好地了解食管癌相关的机制和信号通路。在本研究中,我们从基因表达综合数据库(GEO)下载了微阵列数据集GSE157808和GSE92396。使用R软件鉴定差异表达基因(DEG),并通过GEPIA和TIMER数据库进行验证。使用CytoHubba从重叠的DEG中提取枢纽基因。利用TIMER数据库评估基因表达与免疫浸润之间的相关性。此外,通过RT-qPCR和蛋白质印迹分析了20对EC组织样本中的枢纽基因表达。我们评估了临床病理相关性和诊断潜力。我们在数据集中鉴定出83个重叠的DEG。随后,根据枢纽基因网络中的最高度数,选择了 、 和 基因进行进一步的实验分析。EC样本显示这些基因的表达上调,这与我们的生物信息学分析以及GEPIA和TIMER数据库一致。然而,KRT6B蛋白水平没有显著升高。 表达与淋巴结转移相关,而 与坏死呈负相关。基因表达水平与免疫浸润成分相关。ROC分析表明其具有潜在的诊断价值,而Kaplan-Meier曲线显示与生存结果无显著关联。 、 、 和 的表达升高与EC相关,表明它们作为进一步研究候选物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf24/12226072/880ec12960cb/gr12.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf24/12226072/366da961c206/gr3.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf24/12226072/6cd3912cd9f0/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf24/12226072/7db77a7679ee/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf24/12226072/aa62e88f13c2/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf24/12226072/10ed5a382121/gr10.jpg
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本文引用的文献

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