Identification and Validation of Chromobox Family Members as Potential Prognostic Biomarkers and Therapeutic Targets for Human Esophageal Cancer
Background: Chromobox family proteins (CBXs) are vital components of epigenetic regulation complexes and transcriptionally inhibit target genes by modifying the chromatin. Accumulating evidence indicates that CBXs are involved in the initiation and progression of multiple malignancies. However, the...
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| Format: | Article |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.851390/full |
| _version_ | 1828272437823799296 |
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| author | Xuefen Fang Xuefen Fang Junjun Wang Jiabing Chen Jiabing Chen Mingkai Zhuang Mingkai Zhuang Tingxuan Huang Tingxuan Huang Zhixin Chen Zhixin Chen Yuehong Huang Yuehong Huang Biyun Zheng Biyun Zheng Biyun Zheng Xiaozhong Wang Xiaozhong Wang |
| author_facet | Xuefen Fang Xuefen Fang Junjun Wang Jiabing Chen Jiabing Chen Mingkai Zhuang Mingkai Zhuang Tingxuan Huang Tingxuan Huang Zhixin Chen Zhixin Chen Yuehong Huang Yuehong Huang Biyun Zheng Biyun Zheng Biyun Zheng Xiaozhong Wang Xiaozhong Wang |
| author_sort | Xuefen Fang |
| collection | DOAJ |
| description | Background: Chromobox family proteins (CBXs) are vital components of epigenetic regulation complexes and transcriptionally inhibit target genes by modifying the chromatin. Accumulating evidence indicates that CBXs are involved in the initiation and progression of multiple malignancies. However, the expression, function, and clinical relevance such as the prognostic and diagnostic values of different CBXs in esophageal carcinoma (ESCA) are still unclear.Methods: We applied Oncomine, TCGA, GEO, GEPIA, UALCAN, Kaplan–Meier plotter, cBioPortal, Metascape, and TIMER to investigate the roles of CBX family members in ESCA. Additionally, quantitative real-time PCR (RT-PCR), western blot, and immunofluorescence were used to verify the expression of CBX family members in ESCA clinical samples.Results: Compared with normal tissues, the mRNA expression levels of CBX1/3/8 were significantly increased in ESCA, whereas CBX7 mRNA expression was reduced in both the TCGA cohort and GEO cohort. In the TCGA cohort, ROC curves suggested that CBX1/2/3/4/8 had great diagnostic value in ESCA, and the AUCs were above 0.9. Furthermore, upregulation of CBX1/3/8 and downregulation of CBX7 were closely related to the clinicopathological parameters in ESCA patients, such as tumor grades, tumor nodal metastasis status, and TP53 mutation status. The survival analysis indicated that higher CBX1/3/8 mRNA expressions and lower CBX7 expression suggested an unfavorable prognosis in ESCA. High genetic change rate (52%) of CBXs was found in ESCA patients. Functions and pathways of mutations in CBXs and their 50 frequently altered neighbor genes in ESCA patients were investigated; the results showed that DNA repair and DNA replication were correlated to CBX alterations. Moreover, we found a significant correlation between the expression level of CBX family members and the infiltration of immune cells in ESCA. Finally, we verified the expression of CBX family members in clinical samples and found the results were consistent with the databases.Conclusion: Our study implied that CBX1/3/7/8 are potential targets of precision therapy for ESCA patients and new biomarkers for the prognosis. |
| first_indexed | 2024-04-13T06:06:41Z |
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| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-13T06:06:41Z |
| publishDate | 2022-04-01 |
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| series | Frontiers in Genetics |
| spelling | doaj.art-1256315447dc4d9592d9ec7efe7ed9cd2022-12-22T02:59:13ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-04-011310.3389/fgene.2022.851390851390Identification and Validation of Chromobox Family Members as Potential Prognostic Biomarkers and Therapeutic Targets for Human Esophageal CancerXuefen Fang0Xuefen Fang1Junjun Wang2Jiabing Chen3Jiabing Chen4Mingkai Zhuang5Mingkai Zhuang6Tingxuan Huang7Tingxuan Huang8Zhixin Chen9Zhixin Chen10Yuehong Huang11Yuehong Huang12Biyun Zheng13Biyun Zheng14Biyun Zheng15Xiaozhong Wang16Xiaozhong Wang17Department of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, Fuzhou, ChinaFujian Medical University Cancer Center, Fujian Medical University, Fuzhou, ChinaDepartment of Clinical Laboratory, Fujian Provincial Hospital Southern Branch, Fuzhou, ChinaDepartment of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, Fuzhou, ChinaFujian Medical University Cancer Center, Fujian Medical University, Fuzhou, ChinaDepartment of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, Fuzhou, ChinaFujian Medical University Cancer Center, Fujian Medical University, Fuzhou, ChinaDepartment of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, Fuzhou, ChinaFujian Medical University Cancer Center, Fujian Medical University, Fuzhou, ChinaDepartment of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, Fuzhou, ChinaFujian Medical University Cancer Center, Fujian Medical University, Fuzhou, ChinaDepartment of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, Fuzhou, ChinaFujian Medical University Cancer Center, Fujian Medical University, Fuzhou, ChinaDepartment of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, Fuzhou, ChinaFujian Medical University Cancer Center, Fujian Medical University, Fuzhou, ChinaDepartment of Endoscopy Center, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, Fuzhou, ChinaFujian Medical University Cancer Center, Fujian Medical University, Fuzhou, ChinaBackground: Chromobox family proteins (CBXs) are vital components of epigenetic regulation complexes and transcriptionally inhibit target genes by modifying the chromatin. Accumulating evidence indicates that CBXs are involved in the initiation and progression of multiple malignancies. However, the expression, function, and clinical relevance such as the prognostic and diagnostic values of different CBXs in esophageal carcinoma (ESCA) are still unclear.Methods: We applied Oncomine, TCGA, GEO, GEPIA, UALCAN, Kaplan–Meier plotter, cBioPortal, Metascape, and TIMER to investigate the roles of CBX family members in ESCA. Additionally, quantitative real-time PCR (RT-PCR), western blot, and immunofluorescence were used to verify the expression of CBX family members in ESCA clinical samples.Results: Compared with normal tissues, the mRNA expression levels of CBX1/3/8 were significantly increased in ESCA, whereas CBX7 mRNA expression was reduced in both the TCGA cohort and GEO cohort. In the TCGA cohort, ROC curves suggested that CBX1/2/3/4/8 had great diagnostic value in ESCA, and the AUCs were above 0.9. Furthermore, upregulation of CBX1/3/8 and downregulation of CBX7 were closely related to the clinicopathological parameters in ESCA patients, such as tumor grades, tumor nodal metastasis status, and TP53 mutation status. The survival analysis indicated that higher CBX1/3/8 mRNA expressions and lower CBX7 expression suggested an unfavorable prognosis in ESCA. High genetic change rate (52%) of CBXs was found in ESCA patients. Functions and pathways of mutations in CBXs and their 50 frequently altered neighbor genes in ESCA patients were investigated; the results showed that DNA repair and DNA replication were correlated to CBX alterations. Moreover, we found a significant correlation between the expression level of CBX family members and the infiltration of immune cells in ESCA. Finally, we verified the expression of CBX family members in clinical samples and found the results were consistent with the databases.Conclusion: Our study implied that CBX1/3/7/8 are potential targets of precision therapy for ESCA patients and new biomarkers for the prognosis.https://www.frontiersin.org/articles/10.3389/fgene.2022.851390/fullchromobox (CBX) proteinesophageal cancerbioinformatics analysisprognosisbiomarkerimmunofluorescence |
| spellingShingle | Xuefen Fang Xuefen Fang Junjun Wang Jiabing Chen Jiabing Chen Mingkai Zhuang Mingkai Zhuang Tingxuan Huang Tingxuan Huang Zhixin Chen Zhixin Chen Yuehong Huang Yuehong Huang Biyun Zheng Biyun Zheng Biyun Zheng Xiaozhong Wang Xiaozhong Wang Identification and Validation of Chromobox Family Members as Potential Prognostic Biomarkers and Therapeutic Targets for Human Esophageal Cancer Frontiers in Genetics chromobox (CBX) protein esophageal cancer bioinformatics analysis prognosis biomarker immunofluorescence |
| title | Identification and Validation of Chromobox Family Members as Potential Prognostic Biomarkers and Therapeutic Targets for Human Esophageal Cancer |
| title_full | Identification and Validation of Chromobox Family Members as Potential Prognostic Biomarkers and Therapeutic Targets for Human Esophageal Cancer |
| title_fullStr | Identification and Validation of Chromobox Family Members as Potential Prognostic Biomarkers and Therapeutic Targets for Human Esophageal Cancer |
| title_full_unstemmed | Identification and Validation of Chromobox Family Members as Potential Prognostic Biomarkers and Therapeutic Targets for Human Esophageal Cancer |
| title_short | Identification and Validation of Chromobox Family Members as Potential Prognostic Biomarkers and Therapeutic Targets for Human Esophageal Cancer |
| title_sort | identification and validation of chromobox family members as potential prognostic biomarkers and therapeutic targets for human esophageal cancer |
| topic | chromobox (CBX) protein esophageal cancer bioinformatics analysis prognosis biomarker immunofluorescence |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.851390/full |
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