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Identification and validation of a 21-mRNA prognostic signature in diffuse lower-grade gliomas

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Abstract

Purpose

Diffuse low-grade and intermediate-grade gliomas, also known as lower-grade gliomas (LGGs), are a class of central nervous system tumors. Overall survival varies greatly between patients, highlighting the importance of evaluating exact outcomes to facilitate individualized clinical management. We aimed to identify an mRNA-based prognostic signature to predict the survival of patients with LGGs.

Methods

A total of 874 LGGs from two public datasets were included. Least absolute shrinkage and selection operator (LASSO) Cox regression was used to select the most prognostic mRNAs and build a risk score. A nomogram incorporating the risk score and clinical factors was established for individualized survival prediction. The performance of the nomogram was assessed in the training set (329 patients), internal validation set (140 patients), and external validation set (405 patients).

Results

21 most prognostic mRNAs remained following the LASSO Cox regression. The 21-mRNA signature successfully stratified patients into high- and low-risk groups (P < 0.001 for all datasets in Kaplan–Meier analysis). Subsequent gene set enrichment analysis identified 19 essential biological processes in high-risk LGGs. Furthermore, a nomogram incorporating the risk score, age, grade, and 1p/19q status was developed with favorable calibration and high predictive accuracy in the training set and validation sets (C-index: 0.877, 0.878, and 0.812, respectively).

Conclusion

The 21-mRNA signature has reliable prognostic value for LGGs and might facilitate the effective stratification and individualized management of patients.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (Grant No. 81472370 and 81672506), the Natural Science Foundation of Beijing (Grant No. 7192056), the National High Technology Research and Development Program of China (863 Program, Grant No. 2014AA020610) and the National Basic Research Program of China (973 Program, Grant No. 2014CB542006).

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Authors and Affiliations

  1. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    Lai-Rong Song, Jian-Cong Weng, Xu-Lei Huo, Liang Wang, Huan Li, Da Li, Zhen Wu & Jun-Ting Zhang

  2. China National Clinical Research Center for Neurological Diseases, Beijing, China

    Lai-Rong Song, Jian-Cong Weng, Xu-Lei Huo, Liang Wang, Da Li, Zhen Wu & Jun-Ting Zhang

  3. Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China

    Lai-Rong Song, Jian-Cong Weng, Xu-Lei Huo, Liang Wang, Huan Li, Da Li, Zhen Wu & Jun-Ting Zhang

  4. Beijing Key Laboratory of Brain Tumor, Beijing, China

    Lai-Rong Song, Jian-Cong Weng, Xu-Lei Huo, Liang Wang, Huan Li, Da Li, Zhen Wu & Jun-Ting Zhang

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  1. Lai-Rong Song
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Song, LR., Weng, JC., Huo, XL. et al. Identification and validation of a 21-mRNA prognostic signature in diffuse lower-grade gliomas. J Neurooncol 146, 207–217 (2020). https://doi.org/10.1007/s11060-019-03372-z

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