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

作者全名："Long, Fei; Ma, Haodong; Hao, Youjin; Tian, Luyao; Li, Yinghong; Li, Bo; Chen, Juan; Tang, Ying; Li, Jing; Deng, Lili; Xie, Guoming; Liu, Mingwei"

作者地址："[Long, Fei; Ma, Haodong; Tian, Luyao; Chen, Juan; Tang, Ying; Li, Jing; Deng, Lili; Xie, Guoming; Liu, Mingwei] Chongqing Med Univ, Coll Lab Med, Key Lab Clin Lab Diagnost, Chongqing 400016, Peoples R China; [Hao, Youjin; Li, Bo] Chongqing Normal Univ, Coll Life Sci, Chongqing 401331, Peoples R China; [Li, Yinghong] Chongqing Univ Posts & Telecommun, Key Lab Big Data Bio Intelligence, Chongqing 400065, Peoples R China"

通信作者："Xie, GM; Liu, MW (通讯作者)，Chongqing Med Univ, Coll Lab Med, Key Lab Clin Lab Diagnost, Chongqing 400016, Peoples R China."

来源：COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001007079100001

JCR分区：Q2

影响因子：4.4

年份：2023

卷号：21

期号：　

开始页：3010

结束页：3023

文献类型：Article

关键词：Breast cancer; Tumor heterogeneity; Risk stratification; Exosome-derived signature; Prognostic panel

摘要："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 (ClinminexoSIG) 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"". (c) 2023 Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/)."

基金机构："Science Innovation Program of College of Laboratory Medicine, Chongqing Medical University [CX202104]; Natural Science Foundation of Chongqing [cstc2019jcyj-msxmX0271, cstc2021jcyj-msxm0317]; Science and Technology Research Plan Project of Chongqing Education Commission [KJQN202100418]"

基金资助正文："This work was funded by the Science Innovation Program of College of Laboratory Medicine, Chongqing Medical University (CX202104) ; Natural Science Foundation of Chongqing (cstc2019jcyj-msxmX0271, cstc2021jcyj-msxm0317) ; Science and Technology Research Plan Project of Chongqing Education Commission (KJQN202100418) ."