Integrative analysis of TP73 profile prognostic significance in WHO grade II/III glioma
Abstract Due to the extremely intrinsic heterogeneity among glioma patients, the outcomes of these patients are tremendously different. Therefore, the exploitation of novel biomarker classification of glioma is vitally important for deep insight into the essence and predicting the prognosis of gliom...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-07-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.4016 |
| _version_ | 1818728410277478400 |
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| author | Yanming Chen Ye Wang Qiheng He Wen Wang Tan Zhang Zhongyong Wang Jun Dong Qing Lan Jizong Zhao |
| author_facet | Yanming Chen Ye Wang Qiheng He Wen Wang Tan Zhang Zhongyong Wang Jun Dong Qing Lan Jizong Zhao |
| author_sort | Yanming Chen |
| collection | DOAJ |
| description | Abstract Due to the extremely intrinsic heterogeneity among glioma patients, the outcomes of these patients are tremendously different. Therefore, the exploitation of novel biomarker classification of glioma is vitally important for deep insight into the essence and predicting the prognosis of glioma. We aim to analyze the correlation between TP73 mRNA expression, DNA methylated alteration and the prognosis of WHO grade II/III glioma, utilizing bioinformatics to evaluate its significance as a risk‐factor in predicting the prognosis of these glioma patients. The analysis found that TP73 expression was positively correlated with the grade of glioma, and showed a strong correlation with glioma molecular classification, which revealed significantly higher TP73 expression in IDH‐wildtype than in IDH‐mutant subtype of WHO grade II/III glioma. Cox regression analysis indicated that high expression of TP73 shared an independent high‐risk factor impacting the prognosis of WHO grade II/III glioma. We discovered 8 DNA promoter methylation sites with prognostic significance, which were negatively associated with TP73 expression, and positively associated with beneficial overall survival (OS) and progression‐free survival (PFS). Integrating with four independent glioma datasets, subsequent Meta‐analysis verified that low expression of TP73 was closely related to favorable OS, especially in IDH‐mutant subtype. Moreover, we found that 1p/19qCodel/TP73low subgroup shared the most favorable OS, 1p/19qNon−codel/TP73high subgroup suffered the worst OS. Meanwhile, the enrichment analysis of TP73‐related differential mRNAs demonstrated that TP73 aberration in WHO grade II/III glioma might be closely related to cell cycle and P53 signaling pathways. Finally, TP73 expression of 53 glioma specimens was measured by qRT‐PCR, which was consistent with the previous analytical result, and TP73 high‐expression subgroup suffered worse PFS than TP73 low‐expression subgroup. In summary, our funding supports that TP73 gene can perform as a reliable biomarker to evaluate the survival outcome of patients diagnosed with WHO grade II/III glioma. |
| first_indexed | 2024-12-17T22:29:33Z |
| format | Article |
| id | doaj.art-1f287744937247f289faa3a9aa5f012f |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-12-17T22:29:33Z |
| publishDate | 2021-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-1f287744937247f289faa3a9aa5f012f2022-12-21T21:30:14ZengWileyCancer Medicine2045-76342021-07-0110134644465710.1002/cam4.4016Integrative analysis of TP73 profile prognostic significance in WHO grade II/III gliomaYanming Chen0Ye Wang1Qiheng He2Wen Wang3Tan Zhang4Zhongyong Wang5Jun Dong6Qing Lan7Jizong Zhao8Department of Neurosurgery The Second Affiliated Hospital of Soochow University Suzhou ChinaHeath Management Center The Second Affiliated Hospital of Soochow University Suzhou ChinaDepartment of Neurosurgery Beijing Tiantan HospitalCapital Medical University Beijing ChinaDepartment of Neurosurgery Beijing Tiantan HospitalCapital Medical University Beijing ChinaDepartment of Neurosurgery The Second Affiliated Hospital of Soochow University Suzhou ChinaDepartment of Neurosurgery The Second Affiliated Hospital of Soochow University Suzhou ChinaDepartment of Neurosurgery The Second Affiliated Hospital of Soochow University Suzhou ChinaDepartment of Neurosurgery The Second Affiliated Hospital of Soochow University Suzhou ChinaDepartment of Neurosurgery The Second Affiliated Hospital of Soochow University Suzhou ChinaAbstract Due to the extremely intrinsic heterogeneity among glioma patients, the outcomes of these patients are tremendously different. Therefore, the exploitation of novel biomarker classification of glioma is vitally important for deep insight into the essence and predicting the prognosis of glioma. We aim to analyze the correlation between TP73 mRNA expression, DNA methylated alteration and the prognosis of WHO grade II/III glioma, utilizing bioinformatics to evaluate its significance as a risk‐factor in predicting the prognosis of these glioma patients. The analysis found that TP73 expression was positively correlated with the grade of glioma, and showed a strong correlation with glioma molecular classification, which revealed significantly higher TP73 expression in IDH‐wildtype than in IDH‐mutant subtype of WHO grade II/III glioma. Cox regression analysis indicated that high expression of TP73 shared an independent high‐risk factor impacting the prognosis of WHO grade II/III glioma. We discovered 8 DNA promoter methylation sites with prognostic significance, which were negatively associated with TP73 expression, and positively associated with beneficial overall survival (OS) and progression‐free survival (PFS). Integrating with four independent glioma datasets, subsequent Meta‐analysis verified that low expression of TP73 was closely related to favorable OS, especially in IDH‐mutant subtype. Moreover, we found that 1p/19qCodel/TP73low subgroup shared the most favorable OS, 1p/19qNon−codel/TP73high subgroup suffered the worst OS. Meanwhile, the enrichment analysis of TP73‐related differential mRNAs demonstrated that TP73 aberration in WHO grade II/III glioma might be closely related to cell cycle and P53 signaling pathways. Finally, TP73 expression of 53 glioma specimens was measured by qRT‐PCR, which was consistent with the previous analytical result, and TP73 high‐expression subgroup suffered worse PFS than TP73 low‐expression subgroup. In summary, our funding supports that TP73 gene can perform as a reliable biomarker to evaluate the survival outcome of patients diagnosed with WHO grade II/III glioma.https://doi.org/10.1002/cam4.4016biomarkerscancers risk factorsmethylationprognosissurvival |
| spellingShingle | Yanming Chen Ye Wang Qiheng He Wen Wang Tan Zhang Zhongyong Wang Jun Dong Qing Lan Jizong Zhao Integrative analysis of TP73 profile prognostic significance in WHO grade II/III glioma Cancer Medicine biomarkers cancers risk factors methylation prognosis survival |
| title | Integrative analysis of TP73 profile prognostic significance in WHO grade II/III glioma |
| title_full | Integrative analysis of TP73 profile prognostic significance in WHO grade II/III glioma |
| title_fullStr | Integrative analysis of TP73 profile prognostic significance in WHO grade II/III glioma |
| title_full_unstemmed | Integrative analysis of TP73 profile prognostic significance in WHO grade II/III glioma |
| title_short | Integrative analysis of TP73 profile prognostic significance in WHO grade II/III glioma |
| title_sort | integrative analysis of tp73 profile prognostic significance in who grade ii iii glioma |
| topic | biomarkers cancers risk factors methylation prognosis survival |
| url | https://doi.org/10.1002/cam4.4016 |
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