Identification of prognostic biomarkers in the CMTM family genes of human ovarian cancer through bioinformatics analysis and experimental verification

Background: Ovarian cancer (OV) is one of the most common gynecological malignancies worldwide, and its immunotherapy has considerable prospects. Multiple members of the CMTM family were aberrantly expressed in human cancers and controlled key malignant biological processes and immune regulation in...

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Main Authors: Mengjun Zhang, Jialin Wang, Haodi Yue, Lindong Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-08-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2022.918319/full
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author Mengjun Zhang
Jialin Wang
Haodi Yue
Lindong Zhang
author_facet Mengjun Zhang
Jialin Wang
Haodi Yue
Lindong Zhang
author_sort Mengjun Zhang
collection DOAJ
description Background: Ovarian cancer (OV) is one of the most common gynecological malignancies worldwide, and its immunotherapy has considerable prospects. Multiple members of the CMTM family were aberrantly expressed in human cancers and controlled key malignant biological processes and immune regulation in cancer development. However, little is known about the function of this gene family in ovarian cancer, especially in terms of immunity.Methods: GEPIA, Oncomine, HPA, Kaplan–Meier plotter, cBioPortal, GeneMANIA, and TIMER were used to analyze the differential gene expression, prognostic value, genetic alterations, and alterations in the immune microenvironment of the CMTM family in patients with ovarian cancer. Importantly, RT-qPCR was used to verify the gene expression of the CMTM family.Results: CMTM1/3/4/6/7/8 showed abnormally high expression at the mRNA and protein levels in OV tissues based on the GEPIA and HPA databases. RT-qPCR showed that CMTM1/6/8 was highly expressed in ovarian cancer cell lines. IHC verified that CMTM8 is highly expressed in ovarian cancer tissues and is closely related to Ki-67. Survival analysis showed that high expression of CMTM1/2/3/5/8 can lead to a significant reduction in overall survival and progression-free survival. There were many types of genetic alterations in the CMTM family. Also, CMTM1/2/3/6 had a certain correlation with the changes in the immune microenvironment such as immune cell infiltration and immune checkpoint expression, which may be the potential mechanism of the CMTM family in ovarian cancer. IHC verified that CMTM6 is highly expressed in ovarian cancer tissues and is closely related to PD-L1.Conclusion: This study confirmed that the CMTM family has abnormal expression in ovarian cancer and CMTM8 can be used as a biomarker for prognostic evaluation. Also, the CMTM family may be used as a potential target for immunotherapy based on the suppression of immune checkpoints.
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spelling doaj.art-1ca991f38bbd42d38afe2ff1b29557372022-12-22T03:07:50ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-08-011310.3389/fgene.2022.918319918319Identification of prognostic biomarkers in the CMTM family genes of human ovarian cancer through bioinformatics analysis and experimental verificationMengjun Zhang0Jialin Wang1Haodi Yue2Lindong Zhang3Department of Gynecology, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Orthopedics, Capital Medical University Xuanwu Hospital, Beijing, ChinaDepartment of Center for Clinical Single Cell Biomedicine, Henan Provincial People’s Hospital, Zhengzhou, ChinaDepartment of Gynecology, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaBackground: Ovarian cancer (OV) is one of the most common gynecological malignancies worldwide, and its immunotherapy has considerable prospects. Multiple members of the CMTM family were aberrantly expressed in human cancers and controlled key malignant biological processes and immune regulation in cancer development. However, little is known about the function of this gene family in ovarian cancer, especially in terms of immunity.Methods: GEPIA, Oncomine, HPA, Kaplan–Meier plotter, cBioPortal, GeneMANIA, and TIMER were used to analyze the differential gene expression, prognostic value, genetic alterations, and alterations in the immune microenvironment of the CMTM family in patients with ovarian cancer. Importantly, RT-qPCR was used to verify the gene expression of the CMTM family.Results: CMTM1/3/4/6/7/8 showed abnormally high expression at the mRNA and protein levels in OV tissues based on the GEPIA and HPA databases. RT-qPCR showed that CMTM1/6/8 was highly expressed in ovarian cancer cell lines. IHC verified that CMTM8 is highly expressed in ovarian cancer tissues and is closely related to Ki-67. Survival analysis showed that high expression of CMTM1/2/3/5/8 can lead to a significant reduction in overall survival and progression-free survival. There were many types of genetic alterations in the CMTM family. Also, CMTM1/2/3/6 had a certain correlation with the changes in the immune microenvironment such as immune cell infiltration and immune checkpoint expression, which may be the potential mechanism of the CMTM family in ovarian cancer. IHC verified that CMTM6 is highly expressed in ovarian cancer tissues and is closely related to PD-L1.Conclusion: This study confirmed that the CMTM family has abnormal expression in ovarian cancer and CMTM8 can be used as a biomarker for prognostic evaluation. Also, the CMTM family may be used as a potential target for immunotherapy based on the suppression of immune checkpoints.https://www.frontiersin.org/articles/10.3389/fgene.2022.918319/fullCMTM gene familyprognosisovarian cancerimmune microenvironmentbiomarker
spellingShingle Mengjun Zhang
Jialin Wang
Haodi Yue
Lindong Zhang
Identification of prognostic biomarkers in the CMTM family genes of human ovarian cancer through bioinformatics analysis and experimental verification
Frontiers in Genetics
CMTM gene family
prognosis
ovarian cancer
immune microenvironment
biomarker
title Identification of prognostic biomarkers in the CMTM family genes of human ovarian cancer through bioinformatics analysis and experimental verification
title_full Identification of prognostic biomarkers in the CMTM family genes of human ovarian cancer through bioinformatics analysis and experimental verification
title_fullStr Identification of prognostic biomarkers in the CMTM family genes of human ovarian cancer through bioinformatics analysis and experimental verification
title_full_unstemmed Identification of prognostic biomarkers in the CMTM family genes of human ovarian cancer through bioinformatics analysis and experimental verification
title_short Identification of prognostic biomarkers in the CMTM family genes of human ovarian cancer through bioinformatics analysis and experimental verification
title_sort identification of prognostic biomarkers in the cmtm family genes of human ovarian cancer through bioinformatics analysis and experimental verification
topic CMTM gene family
prognosis
ovarian cancer
immune microenvironment
biomarker
url https://www.frontiersin.org/articles/10.3389/fgene.2022.918319/full
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AT haodiyue identificationofprognosticbiomarkersinthecmtmfamilygenesofhumanovariancancerthroughbioinformaticsanalysisandexperimentalverification
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