A novel exosome-derived prognostic signature and risk stratification for breast cancer based on multi-omics and systematic biological heterogeneity

Fei Long; Haodong Ma; Youjin Hao; Luyao Tian; Yinghong Li; Bo Li; Juan Chen; Ying Tang; Jing Li; Lili Deng; Guoming Xie; Mingwei Liu

doi:10.1016/j.csbj.2023.05.013

A novel exosome-derived prognostic signature and risk stratification for breast cancer based on multi-omics and systematic biological heterogeneity

Comput Struct Biotechnol J. 2023 May 12:21:3010-3023. doi: 10.1016/j.csbj.2023.05.013. eCollection 2023.

Authors

Fei Long¹, Haodong Ma¹, Youjin Hao², Luyao Tian¹, Yinghong Li³, Bo Li², Juan Chen¹, Ying Tang¹, Jing Li¹, Lili Deng¹, Guoming Xie¹, Mingwei Liu¹

Affiliations

¹ Key Laboratory of Clinical Laboratory Diagnostics, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, PR China.
² College of Life Sciences, Chongqing Normal University, Chongqing 401331, PR China.
³ Key Laboratory on Big Data for Bio Intelligence, Chongqing University of Posts and Telecommunications, Chongqing 400065, PR China.

Abstract

Tumor heterogeneity remains a major challenge for disease subtyping, risk stratification, and accurate clinical management. Exosome-based liquid biopsy can effectively overcome the limitations of tissue biopsy, achieving minimal invasion, multi-point dynamic monitoring, and good prognosis assessment, and has broad clinical prospects. However, there is still lacking comprehensive analysis of tumor-derived exosome (TDE)-based stratification of risk patients and prognostic assessment for breast cancer with systematic dissection of biological heterogeneity. In this study, the robust corroborative analysis for biomarker discovery (RCABD) strategy was used for the identification of exosome molecules, differential expression verification, risk prediction modeling, heterogenous dissection with multi-ome (6101 molecules), our ExoBCD database (306 molecules), and 53 independent studies (481 molecules). Our results showed that a 10-molecule exosome-derived signature (exoSIG) could successfully fulfill breast cancer risk stratification, making it a novel and accurate exosome prognostic indicator (Cox P = 9.9E-04, HR = 3.3, 95% CI 1.6-6.8). Interestingly, HLA-DQB2 and COL17A1, closely related to tumor metastasis, achieved high performance in prognosis prediction (86.35% contribution) and accuracy (Log-rank P = 0.028, AUC = 85.42%). With the combined information of patient age and tumor stage, they formed a bimolecular risk signature (Clinmin-exoSIG) and a convenient nomogram as operable tools for clinical applications. In conclusion, as an extension of ExoBCD, this study conducted systematic analyses to identify prognostic multi-molecular panel and risk signature, stratify patients and dissect biological heterogeneity based on breast cancer exosomes from a multi-omics perspective. Our results provide an important reference for in-depth exploration of the "biological heterogeneity - risk stratification - prognosis prediction".

Keywords: Breast cancer; Exosome-derived signature; Prognostic panel; Risk stratification; Tumor heterogeneity.