The Prognostic Value of DNA Methylation, Post-Translational Modifications and Correlated with Immune Infiltrates in Gynecologic Cancers

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This study identified CIRBP and INPP5K DNA methylation, alternative splicing, and polyadenylation events as prognostic indicators in gynecologic cancers, linked to T cell infiltration and survival.

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This study analyzed methylation and RNA-seq data with clinical information from gynecologic cancer cohorts to assess whether DNA methylation, alternative splicing (AS), and alternative polyadenylation (APA) events have prognostic value and how they relate to immune infiltrates. It found that mRNA levels of CIRBP and INPP5K were significantly decreased in gynecologic cancers and were negatively associated with overall survival, with qRT-PCR used for verification, and that CIRBP/INPP5K DNA methylation, AS, and APA features were prognostic indicators; it further reported that T-cell activation signaling might be involved and that CIRBP/INPP5K expression correlated with immune infiltration and worse survival, particularly in uterine corpus endometrial carcinoma (UCEC). The paper’s major caveat is that conclusions are derived from bioinformatics analyses of available datasets, with experimental validation limited to qRT-PCR measurement of mRNA levels. Relevance to endometriosis: it does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match related to gynecologic cancers and immune/molecular prognostic biomarkers.

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Abstract

Chunliang Shang,1 Yuan Li,1 Zhangxin Wu,1 Qin Han,1 Yuan Zhu,2 Tianhui He,1 Hongyan Guo1,3 1Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, People’s Republic of China; 2Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 3National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing 100191, People’s Republic of ChinaCorrespondence: Hongyan GuoDepartment of Obstetrics and Gynecology, Peking University Third Hospital, No. 49 Huayuan North Road, Haidian District, Beijing 100191, People’s Republic of ChinaTel +86-17301281996Fax +86 1082267842Email [email protected]: To depict the prognostic landscape of gynecological cancers from the perspective of DNA methylation, alternative splicing (AS) and polyadenylation (APA) events and investigate their correlation with immune infiltrates.Methods: Methylation and RNA-seq data and corresponding clinical information regarding gynecologic cancers were used to explore the relationships between changes in DNA methylation, AS and APA events and gynecologic cancer prognosis. QRT-PCR and multiple bioinformatics tools were employed to construct a gene interaction network and explore immune infiltrates.Results: Only the mRNA levels of CIRBP and INPP5K were simultaneously significantly decreased in gynecologic cancers and negatively associated with overall survival, which verified by qrt-PCR. We also identified that CIRBP or INPP5K DNA methylation, AS and APA events are prognostic indicators of gynecologic cancers. The activation of T cells might be the main signaling pathway by which these genes modulate cancer progression. CIRBP/INPP5K expression is positively associated with immune infiltration and is a major risk factor of survival, especially among uterine corpus endometrial carcinoma (UCEC) patients.Conclusion: According to these findings, the DNA methylation, AS and APA events of CIRBP and INPP5K may serve as important prognostic biomarkers and targets in gynecological cancers by modulating T cell infiltration.Keywords: DNA methylation, alternative splicing, alternative polyadenylation, activation of T cells, immune infiltration
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Pharmacogenomics and Personalized Medicine (Jan 2021) The Prognostic Value of DNA Methylation, Post-Translational Modifications and Correlated with Immune Infiltrates in Gynecologic Cancers Abstract Chunliang Shang,1 Yuan Li,1 Zhangxin Wu,1 Qin Han,1 Yuan Zhu,2 Tianhui He,1 Hongyan Guo1,3 1Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, People’s Republic of China; 2Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 3National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing 100191, People’s Republic of ChinaCorrespondence: Hongyan GuoDepartment of Obstetrics and Gynecology, Peking University Third Hospital, No. 49 Huayuan North Road, Haidian District, Beijing 100191, People’s Republic of ChinaTel +86-17301281996Fax +86 1082267842Email [email protected]: To depict the prognostic landscape of gynecological cancers from the perspective of DNA methylation, alternative splicing (AS) and polyadenylation (APA) events and investigate their correlation with immune infiltrates.Methods: Methylation and RNA-seq data and corresponding clinical information regarding gynecologic cancers were used to explore the relationships between changes in DNA methylation, AS and APA events and gynecologic cancer prognosis. QRT-PCR and multiple bioinformatics tools were employed to construct a gene interaction network and explore immune infiltrates.Results: Only the mRNA levels of CIRBP and INPP5K were simultaneously significantly decreased in gynecologic cancers and negatively associated with overall survival, which verified by qrt-PCR. We also identified that CIRBP or INPP5K DNA methylation, AS and APA events are prognostic indicators of gynecologic cancers. The activation of T cells might be the main signaling pathway by which these genes modulate cancer progression. CIRBP/INPP5K expression is positively associated with immune infiltration and is a major risk factor of survival, especially among uterine corpus endometrial carcinoma (UCEC) patients.Conclusion: According to these findings, the DNA methylation, AS and APA events of CIRBP and INPP5K may serve as important prognostic biomarkers and targets in gynecological cancers by modulating T cell infiltration.Keywords: DNA methylation, alternative splicing, alternative polyadenylation, activation of T cells, immune infiltration

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