Development and Validation of a Novel Gene Signature for Predicting the Prognosis by Identifying m5C Modification Subtypes of Cervical Cancer
Background: 5-Methylcytidine (m5C) is the most common RNA modification and plays an important role in multiple tumors including cervical cancer (CC). We aimed to develop a novel gene signature by identifying m5C modification subtypes of CC to better predict the prognosis of patients.Methods: We obta...
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| Format: | Article |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.733715/full |
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| author | Jing Yu Lei-Lei Liang Jing Liu Ting-Ting Liu Jian Li Lin Xiu Jia Zeng Tian-Tian Wang Di Wang Li-Jun Liang Da-Wei Xie Ding-Xiong Chen Ju-Sheng An Ling-Ying Wu |
| author_facet | Jing Yu Lei-Lei Liang Jing Liu Ting-Ting Liu Jian Li Lin Xiu Jia Zeng Tian-Tian Wang Di Wang Li-Jun Liang Da-Wei Xie Ding-Xiong Chen Ju-Sheng An Ling-Ying Wu |
| author_sort | Jing Yu |
| collection | DOAJ |
| description | Background: 5-Methylcytidine (m5C) is the most common RNA modification and plays an important role in multiple tumors including cervical cancer (CC). We aimed to develop a novel gene signature by identifying m5C modification subtypes of CC to better predict the prognosis of patients.Methods: We obtained the expression of 13 m5C regulatory factors from The Cancer Genome Atlas (TCGA all set, 257 patients) to determine m5C modification subtypes by the “nonnegative matrix factorization” (NMF). Then the “limma” package was used to identify differentially expressed genes (DEGs) between different subtypes. According to these DEGs, we performed Cox regression and Kaplan-Meier (KM) survival analysis to establish a novel gene signature in TCGA training set (128 patients). We also verified the risk prediction effect of gene signature in TCGA test set (129 patients), TCGA all set (257 patients) and GSE44001 (300 patients). Furthermore, a nomogram including this gene signature and clinicopathological parameters was established to predict the individual survival rate. Finally, the expression and function of these signature genes were explored by qRT-PCR, immunohistochemistry (IHC) and proliferation, colony formation, migration and invasion assays.Results: Based on consistent clustering of 13 m5C-modified genes, CC was divided into two subtypes (C1 and C2) and the C1 subtype had a worse prognosis. The 4-gene signature comprising FNDC3A, VEGFA, OPN3 and CPE was constructed. In TCGA training set and three validation sets, we found the prognosis of patients in the low-risk group was much better than that in the high-risk group. A nomogram incorporating the gene signature and T stage was constructed, and the calibration plot suggested that it could accurately predict the survival rate. The expression levels of FNDC3A, VEGFA, OPN3 and CPE were all high in cervical cancer tissues. Downregulation of FNDC3A, VEGFA or CPE expression suppressed the proliferation, migration and invasion of SiHa cells.Conclusions: Two m5C modification subtypes of CC were identified and then a 4-gene signature was established, which provide new feasible methods for clinical risk assessment and targeted therapies for CC. |
| first_indexed | 2024-12-18T00:37:55Z |
| format | Article |
| id | doaj.art-ec24133d7a6444dfac7b4a729e0386b6 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-18T00:37:55Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-ec24133d7a6444dfac7b4a729e0386b62022-12-21T21:26:58ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-09-011210.3389/fgene.2021.733715733715Development and Validation of a Novel Gene Signature for Predicting the Prognosis by Identifying m5C Modification Subtypes of Cervical CancerJing Yu0Lei-Lei Liang1Jing Liu2Ting-Ting Liu3Jian Li4Lin Xiu5Jia Zeng6Tian-Tian Wang7Di Wang8Li-Jun Liang9Da-Wei Xie10Ding-Xiong Chen11Ju-Sheng An12Ling-Ying Wu13Department of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Blood Grouping, Beijing Red Cross Blood Center, Beijing, ChinaDepartment of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBackground: 5-Methylcytidine (m5C) is the most common RNA modification and plays an important role in multiple tumors including cervical cancer (CC). We aimed to develop a novel gene signature by identifying m5C modification subtypes of CC to better predict the prognosis of patients.Methods: We obtained the expression of 13 m5C regulatory factors from The Cancer Genome Atlas (TCGA all set, 257 patients) to determine m5C modification subtypes by the “nonnegative matrix factorization” (NMF). Then the “limma” package was used to identify differentially expressed genes (DEGs) between different subtypes. According to these DEGs, we performed Cox regression and Kaplan-Meier (KM) survival analysis to establish a novel gene signature in TCGA training set (128 patients). We also verified the risk prediction effect of gene signature in TCGA test set (129 patients), TCGA all set (257 patients) and GSE44001 (300 patients). Furthermore, a nomogram including this gene signature and clinicopathological parameters was established to predict the individual survival rate. Finally, the expression and function of these signature genes were explored by qRT-PCR, immunohistochemistry (IHC) and proliferation, colony formation, migration and invasion assays.Results: Based on consistent clustering of 13 m5C-modified genes, CC was divided into two subtypes (C1 and C2) and the C1 subtype had a worse prognosis. The 4-gene signature comprising FNDC3A, VEGFA, OPN3 and CPE was constructed. In TCGA training set and three validation sets, we found the prognosis of patients in the low-risk group was much better than that in the high-risk group. A nomogram incorporating the gene signature and T stage was constructed, and the calibration plot suggested that it could accurately predict the survival rate. The expression levels of FNDC3A, VEGFA, OPN3 and CPE were all high in cervical cancer tissues. Downregulation of FNDC3A, VEGFA or CPE expression suppressed the proliferation, migration and invasion of SiHa cells.Conclusions: Two m5C modification subtypes of CC were identified and then a 4-gene signature was established, which provide new feasible methods for clinical risk assessment and targeted therapies for CC.https://www.frontiersin.org/articles/10.3389/fgene.2021.733715/fullcervical cancerm5C modificationsignatureprognosisTCGA |
| spellingShingle | Jing Yu Lei-Lei Liang Jing Liu Ting-Ting Liu Jian Li Lin Xiu Jia Zeng Tian-Tian Wang Di Wang Li-Jun Liang Da-Wei Xie Ding-Xiong Chen Ju-Sheng An Ling-Ying Wu Development and Validation of a Novel Gene Signature for Predicting the Prognosis by Identifying m5C Modification Subtypes of Cervical Cancer Frontiers in Genetics cervical cancer m5C modification signature prognosis TCGA |
| title | Development and Validation of a Novel Gene Signature for Predicting the Prognosis by Identifying m5C Modification Subtypes of Cervical Cancer |
| title_full | Development and Validation of a Novel Gene Signature for Predicting the Prognosis by Identifying m5C Modification Subtypes of Cervical Cancer |
| title_fullStr | Development and Validation of a Novel Gene Signature for Predicting the Prognosis by Identifying m5C Modification Subtypes of Cervical Cancer |
| title_full_unstemmed | Development and Validation of a Novel Gene Signature for Predicting the Prognosis by Identifying m5C Modification Subtypes of Cervical Cancer |
| title_short | Development and Validation of a Novel Gene Signature for Predicting the Prognosis by Identifying m5C Modification Subtypes of Cervical Cancer |
| title_sort | development and validation of a novel gene signature for predicting the prognosis by identifying m5c modification subtypes of cervical cancer |
| topic | cervical cancer m5C modification signature prognosis TCGA |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.733715/full |
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