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Systematic Evaluation of Paired Primary and Recurrent Gliomas Identifies Key Genetic Markers for Survival and Therapeutic Targets

43 Pages Posted: 6 Dec 2018

See all articles by Wei Yu

Wei Yu

Zhejiang University

Zhanhuai Wang

Zhejiang University

Xiaoqiu Ren

Zhejiang University

Yongjie Shu

Zhejiang University

Yanqin Huang

Zhejiang University

Bicheng Zhang

Zhejiang University

Zexin Chen

Zhejiang University

Xianglong Li

Zhejiang University

Juan Zhou

Zhejiang University

Yinglu Guo

Zhejiang University

Jing Xu

Zhejiang University

Jinghong Xu

Zhejiang University

Xiao-Fang Yu

Zhejiang University - Ministry of Education Key Laboratory of Cancer Prevention and Intervention

Qichun Wei

Zhejiang University - Ministry of Education Key Laboratory of Cancer Prevention and Intervention; Zhejiang University - Department of Radiation Oncology

More...

Abstract

Background: The differences in genetic characteristics between primary and recurrent gliomas have been poorly characterized. We investigated whether genetic characteristics in recurrent gliomas would differ from those of primary gliomas, as a means of identifying unique markers in recurrent glioma to permit a better understanding of disease progression and therapeutic considerations.    

Methods: Multiple genes involved in eight important pathways in primary and their corresponding paired recurrent glioma samples from 42 patients were analyzed by immunohistochemical staining.    

Findings: In recurrent glioma, we saw a significantly increased expression of PD-1, PD-L1, VEGF, VEGFR2, CD133, MGMT, and Rad51 when compared with their corresponding primary tumors. VEGF expression was correlated with VEGFR2 expression in both primary and recurrent gliomas, and their co-expression was associated with shorter progression-free survival (PFS) and overall survival (OS). PD-1 expression was correlated with PD-L1 expression in recurrent gliomas. As compared to primary gliomas, the overall expression of MGMT was increased in the adjuvant therapy group but was not statistically different from the no-adjuvant therapy group. The group in which MGMT increased had a shorter PFS and OS than did the group in which MGMT was not increased. Co-expression of P53 and Ki-67 in recurrent gliomas was associated with poor median OS after second resection.    

Interpretation: The gene expression characteristics of recurrent gliomas were significantly different from those of their corresponding primary gliomas, a result that has important implications for patient survival. Treatment based on these newly identified changes may offer better therapeutic options for recurrent glioma.  

Funding Statement: This work was surported by the National Natural Science Foundation of China
(81572952).

Declaration of Interests: The authors declare that they have no conflict of interest.

Ethics Approval Statement:  This study was approved by the Ethics Committee of SAHZU, and was carried out in accordance with the Declaration of Helsinki.

Keywords: glioma; recurrence; prognosis; biomarkers

Suggested Citation

Yu, Wei and Wang, Zhanhuai and Ren, Xiaoqiu and Shu, Yongjie and Huang, Yanqin and Zhang, Bicheng and Chen, Zexin and Li, Xianglong and Zhou, Juan and Guo, Yinglu and Xu, Jing and Xu, Jinghong and Yu, Xiao-Fang and Wei, Qichun, Systematic Evaluation of Paired Primary and Recurrent Gliomas Identifies Key Genetic Markers for Survival and Therapeutic Targets (November 30, 2018). Available at SSRN: https://ssrn.com/abstract=3294756

Wei Yu

Zhejiang University ( email )

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Zhanhuai Wang

Zhejiang University ( email )

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Xiaoqiu Ren

Zhejiang University ( email )

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Yongjie Shu

Zhejiang University ( email )

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Yanqin Huang

Zhejiang University ( email )

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Bicheng Zhang

Zhejiang University ( email )

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Zexin Chen

Zhejiang University ( email )

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Xianglong Li

Zhejiang University ( email )

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Juan Zhou

Zhejiang University ( email )

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Yinglu Guo

Zhejiang University ( email )

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Jing Xu

Zhejiang University ( email )

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Jinghong Xu

Zhejiang University ( email )

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Xiao-Fang Yu

Zhejiang University - Ministry of Education Key Laboratory of Cancer Prevention and Intervention ( email )

Jiefang Road 88
Hangzhou, 310009
China

Qichun Wei (Contact Author)

Zhejiang University - Ministry of Education Key Laboratory of Cancer Prevention and Intervention ( email )

Jiefang Road 88
Hangzhou, 310009
China

Zhejiang University - Department of Radiation Oncology ( email )

Hangzhou, 310009
China

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