Extracellular Vesicular Delta‐Like Ligand 3 and Subtype Transcription Factors for Small Cell Lung Cancer Diagnosis
Small cell lung cancer (SCLC) is associated with high mortality and limited therapeutic options. There is increasing recognition that SCLC harbors molecular heterogeneity. Using a new liquid biopsy assay, it is demonstrated that SCLC subtypes, as determined by patient tumor tissue staining and cell lines, can be accurately identified by measuring the mRNA expression of subtype transcription factors (ASCL1, POU2F3, and NEUROD1) in circulating exosome-rich extracellular vesicles (Exo). Additionally, upregulation of Delta-like ligand 3 (DLL3) mRNA in Exo and its membrane protein (mProtein) in extracellular vesicles associated with tumor (tEV) may distinguish both limited- and extensive-stage SCLC patients from high-risk smokers, with AUC/ROC values of 0.836 and 0.839, respectively. By incorporating Exo-ASCL1 and Exo-POU2F3 mRNA expression with DLL3 Exo-mRNA/tEV-mProtein expression, the classifier enhances the AUC/ROC to 0.912 and 0.963 for limited- and extensive-stage SCLC patients, respectively.
Authors
- Giulia Romano (ORCID: https://orcid.org/0000-0001-5847-4266)
- Chi‐Ying F. Huang (ORCID: https://orcid.org/0000-0003-4898-4937)
- Tai‐Shan Cheng
- Xiaokui Molly Mo (ORCID: https://orcid.org/0000-0002-9797-2687)
- Michela Saviana (ORCID: https://orcid.org/0000-0003-2915-8752)
- Yi‐Chen Yeh (ORCID: https://orcid.org/0000-0002-6442-4967)
- Xilal Y. Rima (ORCID: https://orcid.org/0000-0001-5633-5887)
- Robin Toft
- Yifan Ma (ORCID: https://orcid.org/0000-0002-9371-4365)
- Chi‐Ling Chiang (ORCID: https://orcid.org/0000-0002-0275-9673)
- Chia‐Ning Shen (ORCID: https://orcid.org/0000-0002-0747-217X)
- L. James Lee (ORCID: https://orcid.org/0000-0002-3589-0280)
- Chi‐Lu Chiang (ORCID: https://orcid.org/0000-0003-1093-0669)
- Hsin‐Lun Lee (ORCID: https://orcid.org/0000-0002-2905-7858)
- G. Y. Liu
- Peter Mu‐Hsin Chang (ORCID: https://orcid.org/0000-0003-1005-6545)
- Eduardo Reátegui (ORCID: https://orcid.org/0000-0002-8271-8205)
- Patrick Nana‐Sinkam
- Bi‐Da Hsiang
- Tae‐Wan Kim (ORCID: https://orcid.org/0000-0002-7202-009X)
- Hong Li (ORCID: https://orcid.org/0000-0001-5731-5335)
- Xinyu Wang (ORCID: https://orcid.org/0000-0002-7373-5230)
- Yeh‐Shiu Chu (ORCID: https://orcid.org/0000-0002-5388-380X)
- Junjie Pan (ORCID: https://orcid.org/0000-0002-5481-2552)
- Yueh‐Shih Chang
- Kwang Joo Kwak
- Carlo M. Croce
- David P. Carbone
Institutions
- National Yang Ming Chiao Tung University (TW)
- Chang Gung University (TW)
- Virginia Commonwealth University (US)
- Taipei Medical University Hospital (TW)
- Taipei Veterans General Hospital (TW)
- Genomics Research Center, Academia Sinica (TW)
- Keelung Chang Gung Memorial Hospital (TW)
- Taipei Medical University (TW)
- The Ohio State University (US)
- Academia Sinica (TW)
Publication Details
- Journal
- Advanced Science
- Published
- 2025-04-26
- DOI
- https://doi.org/10.1002/advs.202416711
- Citations
- 3
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 2.42
Funders
- Ohio State University
- Ministry of Science and Technology
- Virginia Commonwealth University
- Ministry of Education
- Shanghai Educational Development Foundation
- Ministry of Education, India
- Taipei Medical University
- Taipei Veterans General Hospital
- National Science and Technology Council
- National Institutes of Health
- Chong Hin Loon Memorial Cancer and Biotherapy Research Center, National Yang-Ming University
- National Cancer Institute