4.8 Article

Secretome of Activated Fibroblasts Induced by Exosomes for the Discovery of Biomarkers in Non-Small Cell Lung Cancer

Journal

SMALL
Volume 17, Issue 4, Pages -

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.202004750

Keywords

diagnosis; exosomes; extracellular matrix; non‐ small cell lung cancer; prognosis

Funding

  1. Strategic Priority Research Program of Chinese Academy of Sciences [XDB38030400]
  2. Projects of International Cooperation and Exchanges from the National Natural Science Foundation of China [31161120358]
  3. National Key R&D Program of China [2016YFA0101900]
  4. Key Research Program of the Chinese Academy of Sciences [KJZD-EW-L14]
  5. Key Laboratory of Genomic and Precision Medicine, Chinese Academy of Sciences

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This study uses quantitative proteomics to identify diagnostic markers and a prognostic signature based on differential protein secretion by normal fibroblasts and exosome-activated fibroblasts affected by lung cancer cell-derived exosomes. These findings have the potential to distinguish tumor tissues from normal tissue and identify patients who may benefit from adjuvant therapy after surgical resection. Additionally, the secretome offers novel targets for clinical treatment.
Molecules involved in crosstalk between tumor cells and fibroblasts play vital roles in tumor progression. Extracellular matrix proteins, whose abundance is altered after being affected by tumor-derived exosomes, possess considerable promise as biomarkers for diagnosis or prognosis. In this study, quantitative proteomics is employed to determine the abundance of proteins secreted by normal fibroblasts and exosome-activated fibroblasts, which first identify differentially secreted proteins affected by lung cancer cell-derived exosomes. Based on the differentially secreted proteins and multiple independent datasets comprising 1897 patient samples with non-small cell lung carcinoma or other lung diseases, a diagnostic marker is identified that can effectively distinguish tumor tissues from normal tissue, as well as tumor-associated stroma from normal stroma, and a five-gene prognostic signature is presented with independent prognostic impact to identify patients who may require further adjuvant therapy after surgical resection. In addition, the secretome provides novel potential targets for clinical treatment.

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