Identification and validation of IRF6 related to ovarian cancer and biological function and prognostic value

Abstract Background Ovarian cancer (OC) is a severe gynecological malignancy with significant diagnostic and therapeutic challenges. The discovery of reliable cancer biomarkers can be used to adjust diagnosis and improve patient care. However, serous OC lacks effective biomarkers. We aimed to identi...

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Main Authors: Shihao Hong, Ni Fu, Shanliang Sang, Xudong Ma, Fangying Sun, Xiao Zhang
Format: Article
Language:English
Published: BMC 2024-03-01
Series:Journal of Ovarian Research
Subjects:
Online Access:https://doi.org/10.1186/s13048-024-01386-4
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author Shihao Hong
Ni Fu
Shanliang Sang
Xudong Ma
Fangying Sun
Xiao Zhang
author_facet Shihao Hong
Ni Fu
Shanliang Sang
Xudong Ma
Fangying Sun
Xiao Zhang
author_sort Shihao Hong
collection DOAJ
description Abstract Background Ovarian cancer (OC) is a severe gynecological malignancy with significant diagnostic and therapeutic challenges. The discovery of reliable cancer biomarkers can be used to adjust diagnosis and improve patient care. However, serous OC lacks effective biomarkers. We aimed to identify novel biomarkers for OC and their pathogenic causes. Methods The present study used the differentially expressed genes (DEGs) obtained from the “Limma” package and WGCNA modules for intersection analysis to obtain DEGs in OC. Three hub genes were identified—claudin 3 (CLDN3), interferon regulatory factor 6 (IRF6), and prostasin (PRSS8)—by searching for hub genes through the PPI network and verifying them in GSE14407, GSE18520, GSE66957, and TCGA + GTEx databases. The correlation between IRF6 and the prognosis of OC patients was further confirmed in Kaplan-Miller Plotter. RT-qPCR and IHC confirmed the RNA and protein levels of IRF6 in the OC samples. The effect of IRF6 on OC was explored using transwell invasion and scratch wound assays. Finally, we constructed a ceRNA network of hub genes and used bioinformatics tools to predict drug sensitivity. Results The joint analysis results of TCGA, GTEx, and GEO databases indicated that IRF6 RNA and protein levels were significantly upregulated in serous OC and were associated with OS and PFS. Cell function experiments revealed that IRF6 knockdown inhibited SKOV3 cell proliferation, migration and invasion. Conclusion IRF6 is closely correlated with OC development and progression and could be considered a novel biomarker and therapeutic target for OC patients.
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spelling doaj.art-02a91a46c21a410690ee16ce5c7fdf832024-03-17T12:35:03ZengBMCJournal of Ovarian Research1757-22152024-03-0117111410.1186/s13048-024-01386-4Identification and validation of IRF6 related to ovarian cancer and biological function and prognostic valueShihao Hong0Ni Fu1Shanliang Sang2Xudong Ma3Fangying Sun4Xiao Zhang5Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityDepartment of Obstetrics and Gynecology, Huangyan Hospital of Chinese MedicineDepartment of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityDepartment of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityDepartment of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityDepartment of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityAbstract Background Ovarian cancer (OC) is a severe gynecological malignancy with significant diagnostic and therapeutic challenges. The discovery of reliable cancer biomarkers can be used to adjust diagnosis and improve patient care. However, serous OC lacks effective biomarkers. We aimed to identify novel biomarkers for OC and their pathogenic causes. Methods The present study used the differentially expressed genes (DEGs) obtained from the “Limma” package and WGCNA modules for intersection analysis to obtain DEGs in OC. Three hub genes were identified—claudin 3 (CLDN3), interferon regulatory factor 6 (IRF6), and prostasin (PRSS8)—by searching for hub genes through the PPI network and verifying them in GSE14407, GSE18520, GSE66957, and TCGA + GTEx databases. The correlation between IRF6 and the prognosis of OC patients was further confirmed in Kaplan-Miller Plotter. RT-qPCR and IHC confirmed the RNA and protein levels of IRF6 in the OC samples. The effect of IRF6 on OC was explored using transwell invasion and scratch wound assays. Finally, we constructed a ceRNA network of hub genes and used bioinformatics tools to predict drug sensitivity. Results The joint analysis results of TCGA, GTEx, and GEO databases indicated that IRF6 RNA and protein levels were significantly upregulated in serous OC and were associated with OS and PFS. Cell function experiments revealed that IRF6 knockdown inhibited SKOV3 cell proliferation, migration and invasion. Conclusion IRF6 is closely correlated with OC development and progression and could be considered a novel biomarker and therapeutic target for OC patients.https://doi.org/10.1186/s13048-024-01386-4Ovarian cancerIRF6Prognosis markerWCGNABioinformatics
spellingShingle Shihao Hong
Ni Fu
Shanliang Sang
Xudong Ma
Fangying Sun
Xiao Zhang
Identification and validation of IRF6 related to ovarian cancer and biological function and prognostic value
Journal of Ovarian Research
Ovarian cancer
IRF6
Prognosis marker
WCGNA
Bioinformatics
title Identification and validation of IRF6 related to ovarian cancer and biological function and prognostic value
title_full Identification and validation of IRF6 related to ovarian cancer and biological function and prognostic value
title_fullStr Identification and validation of IRF6 related to ovarian cancer and biological function and prognostic value
title_full_unstemmed Identification and validation of IRF6 related to ovarian cancer and biological function and prognostic value
title_short Identification and validation of IRF6 related to ovarian cancer and biological function and prognostic value
title_sort identification and validation of irf6 related to ovarian cancer and biological function and prognostic value
topic Ovarian cancer
IRF6
Prognosis marker
WCGNA
Bioinformatics
url https://doi.org/10.1186/s13048-024-01386-4
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