The Expression and Role Analysis of Methylation-Regulated Differentially Expressed Gene UBE2C in Pan-Cancer, Especially for HGSOC

High-grade serous ovarian cancer (HGSOC) is the most fatal gynecological malignant tumor. DNA methylation is associated with the occurrence and development of a variety of tumor types, including HGSOC. However, the signatures regarding DNA methylation changes for HGSOC diagnosis and prognosis are le...

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Main Authors: Jiajia Li, Yating Sun, Xiuling Zhi, Qin Li, Liangqing Yao, Mo Chen
Format: Article
Language:English
Published: MDPI AG 2022-06-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/14/13/3121
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author Jiajia Li
Yating Sun
Xiuling Zhi
Qin Li
Liangqing Yao
Mo Chen
author_facet Jiajia Li
Yating Sun
Xiuling Zhi
Qin Li
Liangqing Yao
Mo Chen
author_sort Jiajia Li
collection DOAJ
description High-grade serous ovarian cancer (HGSOC) is the most fatal gynecological malignant tumor. DNA methylation is associated with the occurrence and development of a variety of tumor types, including HGSOC. However, the signatures regarding DNA methylation changes for HGSOC diagnosis and prognosis are less explored. Here, we screened differentially methylated genes and differentially expressed genes in HGSOC through the GEO database. We identified that UBE2C was hypomethylation and overexpression in ovarian cancer, which was associated with more advanced cancer stages and poor prognoses. Additionally, the pan-cancer analysis showed that UBE2C was overexpressed and hypomethylation in almost all cancer types and was related to poor prognoses for various cancers. Next, we established a risk or prognosis model related to UBE2C methylation sites and screened out the three sites (cg03969725, cg02838589, and cg00242976). Furthermore, we experimentally validated the overexpression of UBE2C in HGSOC clinical samples and ovarian cell lines using quantitative real-time PCR, Western blot, and immunohistochemistry. Importantly, we discovered that ovarian cancer cell lines had lower DNA methylation levels of UBE2C than IOSE-80 cells (normal ovarian epithelial cell line) by bisulfite sequencing PCR. Consistently, treatment with 5-Azacytidine (a methylation inhibitor) was able to restore the expression of UBE2C. Taken together, our study may help us to understand the underlying molecular mechanism of UBE2C in pan-cancer tumorigenesis; it may be a useful biomarker for diagnosis, treatment, and monitoring, not only of ovarian cancer but a variety of cancers.
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spelling doaj.art-5e3849ca08de4a4cb92d2334614e0d3e2023-11-23T19:44:48ZengMDPI AGCancers2072-66942022-06-011413312110.3390/cancers14133121The Expression and Role Analysis of Methylation-Regulated Differentially Expressed Gene UBE2C in Pan-Cancer, Especially for HGSOCJiajia Li0Yating Sun1Xiuling Zhi2Qin Li3Liangqing Yao4Mo Chen5Department of Gynecology Oncology, Obstetrics & Gynecology Hospital, Fudan University, Shanghai 200011, ChinaDepartment of Gynecology Oncology, Obstetrics & Gynecology Hospital, Fudan University, Shanghai 200011, ChinaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, ChinaDepartment of Gynecology Oncology, Obstetrics & Gynecology Hospital, Fudan University, Shanghai 200011, ChinaDepartment of Gynecology Oncology, Obstetrics & Gynecology Hospital, Fudan University, Shanghai 200011, ChinaDepartment of Gynecology Oncology, Obstetrics & Gynecology Hospital, Fudan University, Shanghai 200011, ChinaHigh-grade serous ovarian cancer (HGSOC) is the most fatal gynecological malignant tumor. DNA methylation is associated with the occurrence and development of a variety of tumor types, including HGSOC. However, the signatures regarding DNA methylation changes for HGSOC diagnosis and prognosis are less explored. Here, we screened differentially methylated genes and differentially expressed genes in HGSOC through the GEO database. We identified that UBE2C was hypomethylation and overexpression in ovarian cancer, which was associated with more advanced cancer stages and poor prognoses. Additionally, the pan-cancer analysis showed that UBE2C was overexpressed and hypomethylation in almost all cancer types and was related to poor prognoses for various cancers. Next, we established a risk or prognosis model related to UBE2C methylation sites and screened out the three sites (cg03969725, cg02838589, and cg00242976). Furthermore, we experimentally validated the overexpression of UBE2C in HGSOC clinical samples and ovarian cell lines using quantitative real-time PCR, Western blot, and immunohistochemistry. Importantly, we discovered that ovarian cancer cell lines had lower DNA methylation levels of UBE2C than IOSE-80 cells (normal ovarian epithelial cell line) by bisulfite sequencing PCR. Consistently, treatment with 5-Azacytidine (a methylation inhibitor) was able to restore the expression of UBE2C. Taken together, our study may help us to understand the underlying molecular mechanism of UBE2C in pan-cancer tumorigenesis; it may be a useful biomarker for diagnosis, treatment, and monitoring, not only of ovarian cancer but a variety of cancers.https://www.mdpi.com/2072-6694/14/13/3121ovarian cancerDNA methylationUBE2Cbioinformatics
spellingShingle Jiajia Li
Yating Sun
Xiuling Zhi
Qin Li
Liangqing Yao
Mo Chen
The Expression and Role Analysis of Methylation-Regulated Differentially Expressed Gene UBE2C in Pan-Cancer, Especially for HGSOC
Cancers
ovarian cancer
DNA methylation
UBE2C
bioinformatics
title The Expression and Role Analysis of Methylation-Regulated Differentially Expressed Gene UBE2C in Pan-Cancer, Especially for HGSOC
title_full The Expression and Role Analysis of Methylation-Regulated Differentially Expressed Gene UBE2C in Pan-Cancer, Especially for HGSOC
title_fullStr The Expression and Role Analysis of Methylation-Regulated Differentially Expressed Gene UBE2C in Pan-Cancer, Especially for HGSOC
title_full_unstemmed The Expression and Role Analysis of Methylation-Regulated Differentially Expressed Gene UBE2C in Pan-Cancer, Especially for HGSOC
title_short The Expression and Role Analysis of Methylation-Regulated Differentially Expressed Gene UBE2C in Pan-Cancer, Especially for HGSOC
title_sort expression and role analysis of methylation regulated differentially expressed gene ube2c in pan cancer especially for hgsoc
topic ovarian cancer
DNA methylation
UBE2C
bioinformatics
url https://www.mdpi.com/2072-6694/14/13/3121
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