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

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 GSE1...

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Main Authors: Shayan Marhamati, Morvarid Hamrahjoo, Zeinab Seyedkhan, Mahdi Bahmani, Nasrin Ziamajidi, Iraj Khodadadi, Mohadese Pouryani, Roghayeh Abbasalipourkabir
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Biochemistry and Biophysics Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405580825001827
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author Shayan Marhamati
Morvarid Hamrahjoo
Zeinab Seyedkhan
Mahdi Bahmani
Nasrin Ziamajidi
Iraj Khodadadi
Mohadese Pouryani
Roghayeh Abbasalipourkabir
author_facet Shayan Marhamati
Morvarid Hamrahjoo
Zeinab Seyedkhan
Mahdi Bahmani
Nasrin Ziamajidi
Iraj Khodadadi
Mohadese Pouryani
Roghayeh Abbasalipourkabir
author_sort Shayan Marhamati
collection DOAJ
description 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 KRT6A, KRT6B, PKP1, and PKP3 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. KRT6A expression was associated with lymph node metastasis, while KRT6B 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 KRT6A, KRT6B, PKP1, and PKP3 is associated with EC, indicating their potential as candidates for further investigation.
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spelling doaj-art-e8609436066b45a797b09d9c2dc40f482025-08-20T03:47:19ZengElsevierBiochemistry and Biophysics Reports2405-58082025-09-014310209510.1016/j.bbrep.2025.102095KRT6A, KRT6B, PKP1, and PKP3 as key hub genes in esophageal cancer: A combined bioinformatics and experimental studyShayan Marhamati0Morvarid Hamrahjoo1Zeinab Seyedkhan2Mahdi Bahmani3Nasrin Ziamajidi4Iraj Khodadadi5Mohadese Pouryani6Roghayeh Abbasalipourkabir7Department of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran; Student Research Committee, Hamadan University of Medical Sciences, Hamadan, IranDepartment of Virology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, IranDepartment of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran; Student Research Committee, Hamadan University of Medical Sciences, Hamadan, IranDepartment of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, IranDepartment of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran; Department of Molecular Medicine and Genetics, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, IranDepartment of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, IranDepartment of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, IranDepartment of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran; Corresponding author. Department of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, 6517619657, Hamadan, Iran.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 KRT6A, KRT6B, PKP1, and PKP3 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. KRT6A expression was associated with lymph node metastasis, while KRT6B 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 KRT6A, KRT6B, PKP1, and PKP3 is associated with EC, indicating their potential as candidates for further investigation.http://www.sciencedirect.com/science/article/pii/S2405580825001827Esophageal cancerKRT6AKRT6BPKP1PKP3Diagnosis
spellingShingle Shayan Marhamati
Morvarid Hamrahjoo
Zeinab Seyedkhan
Mahdi Bahmani
Nasrin Ziamajidi
Iraj Khodadadi
Mohadese Pouryani
Roghayeh Abbasalipourkabir
KRT6A, KRT6B, PKP1, and PKP3 as key hub genes in esophageal cancer: A combined bioinformatics and experimental study
Biochemistry and Biophysics Reports
Esophageal cancer
KRT6A
KRT6B
PKP1
PKP3
Diagnosis
title KRT6A, KRT6B, PKP1, and PKP3 as key hub genes in esophageal cancer: A combined bioinformatics and experimental study
title_full KRT6A, KRT6B, PKP1, and PKP3 as key hub genes in esophageal cancer: A combined bioinformatics and experimental study
title_fullStr KRT6A, KRT6B, PKP1, and PKP3 as key hub genes in esophageal cancer: A combined bioinformatics and experimental study
title_full_unstemmed KRT6A, KRT6B, PKP1, and PKP3 as key hub genes in esophageal cancer: A combined bioinformatics and experimental study
title_short KRT6A, KRT6B, PKP1, and PKP3 as key hub genes in esophageal cancer: A combined bioinformatics and experimental study
title_sort krt6a krt6b pkp1 and pkp3 as key hub genes in esophageal cancer a combined bioinformatics and experimental study
topic Esophageal cancer
KRT6A
KRT6B
PKP1
PKP3
Diagnosis
url http://www.sciencedirect.com/science/article/pii/S2405580825001827
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