Key wound healing genes as diagnostic biomarkers and therapeutic targets in uterine corpus endometrial carcinoma: an integrated in silico and in vitro study
Abstract Background Uterine Corpus Endometrial Carcinoma (UCEC) is a prevalent gynecologic malignancy with complex molecular underpinnings. This study identifies key woundhealing genes involved in UCEC and elucidates their roles through a comprehensive analysis. Methods In silico and in vitro experi...
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BMC
2025-01-01
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| Series: | Hereditas |
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| Online Access: | https://doi.org/10.1186/s41065-025-00369-9 |
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| author | Fuchuan Jiang Sajjad Ahmad Sadia kanwal Yasir Hameed Qian Tang |
| author_facet | Fuchuan Jiang Sajjad Ahmad Sadia kanwal Yasir Hameed Qian Tang |
| author_sort | Fuchuan Jiang |
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| description | Abstract Background Uterine Corpus Endometrial Carcinoma (UCEC) is a prevalent gynecologic malignancy with complex molecular underpinnings. This study identifies key woundhealing genes involved in UCEC and elucidates their roles through a comprehensive analysis. Methods In silico and in vitro experiments. Results Seventy wound healing-associated genes were extracted from the Gene Ontology (GO) database, and a protein-protein interaction (PPI) network was constructed using the STRING database. CytoHubba analysis in Cytoscape identified six pivotal hub genes: CD44, FGF2, FGF10, KDM6A, FN1, and MMP2. These genes exhibited significantly lower expression in UCEC cell lines compared to normal controls, as confirmed by RT-qPCR. Receiver Operating Characteristic (ROC) analysis demonstrated their potential as diagnostic biomarkers, with Area Under the Curve (AUC) values ranging from 0.94 to 1.00. Validation using TCGA datasets revealed consistent downregulation of these genes in UCEC samples, corroborated by immunohistochemical staining. Promoter methylation analysis showed significantly higher methylation levels in UCEC, correlating with decreased mRNA expression and poor survival outcomes. Genetic alteration analysis indicated frequent mutations in FN1 and KDM6A, although these did not significantly affect survival. Functional analysis using the CancerSEA database highlighted the involvement of these genes in critical cancer-related processes, including angiogenesis, apoptosis, and metastasis. Immune correlation studies revealed significant associations with immune inhibitor genes and distinct expression patterns across immune subtypes. Overexpression studies in UCEC cell lines demonstrated that CD44 and MMP2 reduce proliferative ability while enhancing migration and wound healing. Conclusion Collectively, these findings underscore the crucial roles of CD44, FGF2, FGF10, KDM6A, FN1, and MMP2 in UCEC pathogenesis, highlighting their potential as biomarkers and therapeutic targets in this malignancy. |
| format | Article |
| id | doaj-art-c270641d114a419fbfb10ed72366f5c5 |
| institution | Kabale University |
| issn | 1601-5223 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Hereditas |
| spelling | doaj-art-c270641d114a419fbfb10ed72366f5c52025-01-26T12:36:40ZengBMCHereditas1601-52232025-01-01162112010.1186/s41065-025-00369-9Key wound healing genes as diagnostic biomarkers and therapeutic targets in uterine corpus endometrial carcinoma: an integrated in silico and in vitro studyFuchuan Jiang0Sajjad Ahmad1Sadia kanwal2Yasir Hameed3Qian Tang4Department of Gynaecology and Obstetrics, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaGomal Medical CollegeAl Nafees Medical College and Hospital IslamabadDepartment of Biochemistry, The Islamia University of BahawalpurDepartment of Gynaecology and Obstetrics, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaAbstract Background Uterine Corpus Endometrial Carcinoma (UCEC) is a prevalent gynecologic malignancy with complex molecular underpinnings. This study identifies key woundhealing genes involved in UCEC and elucidates their roles through a comprehensive analysis. Methods In silico and in vitro experiments. Results Seventy wound healing-associated genes were extracted from the Gene Ontology (GO) database, and a protein-protein interaction (PPI) network was constructed using the STRING database. CytoHubba analysis in Cytoscape identified six pivotal hub genes: CD44, FGF2, FGF10, KDM6A, FN1, and MMP2. These genes exhibited significantly lower expression in UCEC cell lines compared to normal controls, as confirmed by RT-qPCR. Receiver Operating Characteristic (ROC) analysis demonstrated their potential as diagnostic biomarkers, with Area Under the Curve (AUC) values ranging from 0.94 to 1.00. Validation using TCGA datasets revealed consistent downregulation of these genes in UCEC samples, corroborated by immunohistochemical staining. Promoter methylation analysis showed significantly higher methylation levels in UCEC, correlating with decreased mRNA expression and poor survival outcomes. Genetic alteration analysis indicated frequent mutations in FN1 and KDM6A, although these did not significantly affect survival. Functional analysis using the CancerSEA database highlighted the involvement of these genes in critical cancer-related processes, including angiogenesis, apoptosis, and metastasis. Immune correlation studies revealed significant associations with immune inhibitor genes and distinct expression patterns across immune subtypes. Overexpression studies in UCEC cell lines demonstrated that CD44 and MMP2 reduce proliferative ability while enhancing migration and wound healing. Conclusion Collectively, these findings underscore the crucial roles of CD44, FGF2, FGF10, KDM6A, FN1, and MMP2 in UCEC pathogenesis, highlighting their potential as biomarkers and therapeutic targets in this malignancy.https://doi.org/10.1186/s41065-025-00369-9CancerUCECTumor progressionDiagnosisTreatment |
| spellingShingle | Fuchuan Jiang Sajjad Ahmad Sadia kanwal Yasir Hameed Qian Tang Key wound healing genes as diagnostic biomarkers and therapeutic targets in uterine corpus endometrial carcinoma: an integrated in silico and in vitro study Hereditas Cancer UCEC Tumor progression Diagnosis Treatment |
| title | Key wound healing genes as diagnostic biomarkers and therapeutic targets in uterine corpus endometrial carcinoma: an integrated in silico and in vitro study |
| title_full | Key wound healing genes as diagnostic biomarkers and therapeutic targets in uterine corpus endometrial carcinoma: an integrated in silico and in vitro study |
| title_fullStr | Key wound healing genes as diagnostic biomarkers and therapeutic targets in uterine corpus endometrial carcinoma: an integrated in silico and in vitro study |
| title_full_unstemmed | Key wound healing genes as diagnostic biomarkers and therapeutic targets in uterine corpus endometrial carcinoma: an integrated in silico and in vitro study |
| title_short | Key wound healing genes as diagnostic biomarkers and therapeutic targets in uterine corpus endometrial carcinoma: an integrated in silico and in vitro study |
| title_sort | key wound healing genes as diagnostic biomarkers and therapeutic targets in uterine corpus endometrial carcinoma an integrated in silico and in vitro study |
| topic | Cancer UCEC Tumor progression Diagnosis Treatment |
| url | https://doi.org/10.1186/s41065-025-00369-9 |
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