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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Main Authors: Li-Peng Pei, Yun-Zheng Zhang, Guang-Ying Li, Jing-Li Sun
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-06-01
Series:Frontiers in Genetics
Subjects:
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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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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AT guangyingli comprehensiveanalysisoftheexpressionandprognosisformcm4inuterinecorpusendometrialcarcinoma
AT jinglisun comprehensiveanalysisoftheexpressionandprognosisformcm4inuterinecorpusendometrialcarcinoma