Comprehensive Analysis of the Expression and Prognosis for MCM4 in Uterine Corpus Endometrial Carcinoma
Background: Mini chromosome maintenance protein 4 (MCM4) belongs to the family of mini chromosome maintenance proteins (MCMs) that plays a crucial role in DNA replication and cell cycle regulation. Given that MCM4 has been reported to be aberrantly expressed in a variety of tumor tissues, and is str...
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Frontiers Media S.A.
2022-06-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.890591/full |
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author | Li-Peng Pei Yun-Zheng Zhang Guang-Ying Li Jing-Li Sun |
author_facet | Li-Peng Pei Yun-Zheng Zhang Guang-Ying Li Jing-Li Sun |
author_sort | Li-Peng Pei |
collection | DOAJ |
description | Background: Mini chromosome maintenance protein 4 (MCM4) belongs to the family of mini chromosome maintenance proteins (MCMs) that plays a crucial role in DNA replication and cell cycle regulation. Given that MCM4 has been reported to be aberrantly expressed in a variety of tumor tissues, and is strongly associated with poor patient prognosis, it has rarely been reported in uterine corpus endometrial carcinoma (UCEC).Methods: We explored the role of MCM4 in UCEC through multi-omics analysis, including gene expression levels, survival prognosis, the biological function of interacting proteins, immune infiltration, and diagnostic value. Finally, these results were confirmed by biological experiments.Results: MCM4 was highly expressed in various malignancies including UCEC compared to normal samples and was associated with poor prognosis in patients with UCEC [including OS (HR = 1.74, p = 0.009), PFI (HR = 1.73, p = 0.002), PFI (HR = 2.23, p = 0.003)]. In the Cox regression analysis, MCM4 was an independent prognostic biomarker. Further studies showed those interacting proteins of MCM4 were enriched in DNA repair and cell cycle. Moreover, high expression of MCM4 was accompanied by lower infiltration of immune cells such as Treg cells and B cells. The distribution of MCM4 expression in molecular and immune subtypes was significantly different (p < 0.05), with high expression in the copynumber high (CN_HIGH) molecular subtype and the IFN-gamma dominant (C2) immune subtype. RT-qPCR and immunohistochemistry results also showed that MCM4 expression was significantly upregulated in endometrial cancer tissues and negatively correlated with patient prognosis (p < 0.05). Subsequent biological experiments confirmed that MCM4 promoted cell growth and invasion and inhibited apoptosis in vitro.Conclusion: Therefore, MCM4 could be a new potential biomarker for UCEC. |
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language | English |
last_indexed | 2024-04-12T15:39:09Z |
publishDate | 2022-06-01 |
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spelling | doaj.art-a6510ea5de204e0985a449a3992a680c2022-12-22T03:26:53ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-06-011310.3389/fgene.2022.890591890591Comprehensive Analysis of the Expression and Prognosis for MCM4 in Uterine Corpus Endometrial CarcinomaLi-Peng PeiYun-Zheng ZhangGuang-Ying LiJing-Li SunBackground: Mini chromosome maintenance protein 4 (MCM4) belongs to the family of mini chromosome maintenance proteins (MCMs) that plays a crucial role in DNA replication and cell cycle regulation. Given that MCM4 has been reported to be aberrantly expressed in a variety of tumor tissues, and is strongly associated with poor patient prognosis, it has rarely been reported in uterine corpus endometrial carcinoma (UCEC).Methods: We explored the role of MCM4 in UCEC through multi-omics analysis, including gene expression levels, survival prognosis, the biological function of interacting proteins, immune infiltration, and diagnostic value. Finally, these results were confirmed by biological experiments.Results: MCM4 was highly expressed in various malignancies including UCEC compared to normal samples and was associated with poor prognosis in patients with UCEC [including OS (HR = 1.74, p = 0.009), PFI (HR = 1.73, p = 0.002), PFI (HR = 2.23, p = 0.003)]. In the Cox regression analysis, MCM4 was an independent prognostic biomarker. Further studies showed those interacting proteins of MCM4 were enriched in DNA repair and cell cycle. Moreover, high expression of MCM4 was accompanied by lower infiltration of immune cells such as Treg cells and B cells. The distribution of MCM4 expression in molecular and immune subtypes was significantly different (p < 0.05), with high expression in the copynumber high (CN_HIGH) molecular subtype and the IFN-gamma dominant (C2) immune subtype. RT-qPCR and immunohistochemistry results also showed that MCM4 expression was significantly upregulated in endometrial cancer tissues and negatively correlated with patient prognosis (p < 0.05). Subsequent biological experiments confirmed that MCM4 promoted cell growth and invasion and inhibited apoptosis in vitro.Conclusion: Therefore, MCM4 could be a new potential biomarker for UCEC.https://www.frontiersin.org/articles/10.3389/fgene.2022.890591/fullMCM4uterine corpus endometrial carcinomaprognosismulti-omics analysisRT-qPCRimmunohistochemistry |
spellingShingle | Li-Peng Pei Yun-Zheng Zhang Guang-Ying Li Jing-Li Sun Comprehensive Analysis of the Expression and Prognosis for MCM4 in Uterine Corpus Endometrial Carcinoma Frontiers in Genetics MCM4 uterine corpus endometrial carcinoma prognosis multi-omics analysis RT-qPCR immunohistochemistry |
title | Comprehensive Analysis of the Expression and Prognosis for MCM4 in Uterine Corpus Endometrial Carcinoma |
title_full | Comprehensive Analysis of the Expression and Prognosis for MCM4 in Uterine Corpus Endometrial Carcinoma |
title_fullStr | Comprehensive Analysis of the Expression and Prognosis for MCM4 in Uterine Corpus Endometrial Carcinoma |
title_full_unstemmed | Comprehensive Analysis of the Expression and Prognosis for MCM4 in Uterine Corpus Endometrial Carcinoma |
title_short | Comprehensive Analysis of the Expression and Prognosis for MCM4 in Uterine Corpus Endometrial Carcinoma |
title_sort | comprehensive analysis of the expression and prognosis for mcm4 in uterine corpus endometrial carcinoma |
topic | MCM4 uterine corpus endometrial carcinoma prognosis multi-omics analysis RT-qPCR immunohistochemistry |
url | https://www.frontiersin.org/articles/10.3389/fgene.2022.890591/full |
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