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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2022

01-12-2022 | Glioma | Research

An integrative multi-omics analysis based on liquid–liquid phase separation delineates distinct subtypes of lower-grade glioma and identifies a prognostic signature

Authors: Jianglin Zheng, Zhipeng Wu, Yue Qiu, Xuan Wang, Xiaobing Jiang

Published in: Journal of Translational Medicine | Issue 1/2022

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Abstract

Background

Emerging evidences have indicated that the aberrant liquid–liquid phase separation (LLPS) leads to the dysfunction of biomolecular condensates, thereby contributing to the tumorigenesis and progression. Nevertheless, it remains unclear whether or how the LLPS of specific molecules affects the prognosis and tumor immune microenvironment (TIME) of patients with lower-grade glioma (LGG).

Methods

We integrated the transcriptome information of 3585 LLPS-related genes to comprehensively evaluate the LLPS patterns of 423 patients with LGG in The Cancer Genome Atlas (TCGA) cohort. Then, we systematically demonstrated the differences among four LLPS subtypes based on multi-omics analyses. In addition, we constructed the LLPS-related prognostic risk score (LPRS) for individualized integrative assessment.

Results

Based on the expression profiles of 85 scaffolds, 355 regulators, and 3145 clients in LGG, we identified four LLPS subtypes, namely LS1, LS2, LS3 and LS4.
We confirmed that there were significant differences in prognosis, clinicopathological features, cancer hallmarks, genomic alterations, TIME patterns and immunotherapeutic responses among four LLPS subtypes. In addition, a prognostic signature called LPRS was constructed for individualized integrative assessment. LPRS exhibited a robust predictive capacity for prognosis of LGG patients in multiple cohorts. Moreover, LPRS was found to be correlated with clinicopathological features, cancer hallmarks, genomic alterations and TIME patterns of LGG patients. The predictive power of LPRS in response to immune checkpoint inhibitor (ICI) therapy was also prominent.

Conclusions

This study provided a novel classification of LGG patients based on LLPS. The constructed LPRS might facilitate individualized prognosis prediction and better immunotherapy options for LGG patients.
Appendix
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Metadata
Title
An integrative multi-omics analysis based on liquid–liquid phase separation delineates distinct subtypes of lower-grade glioma and identifies a prognostic signature
Authors
Jianglin Zheng
Zhipeng Wu
Yue Qiu
Xuan Wang
Xiaobing Jiang
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-022-03266-1

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