Proteomics-Empowered Microfluidic-SERS Immunoassay for Identifying and Detecting Biomarkers of Micropapillary Lung Adenocarcinoma.

Adv Sci (Weinh)

Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, Fujian Normal University, Fuzhou, Fujian, 350117, China.

Published: July 2025


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Article Abstract

The presence of a micropapillary (MPP) component is a crucial determinant of surgical strategies for lung adenocarcinoma (LUAD), yet reliable blood biomarkers for predicting MPP⁺ LUAD remain elusive. Here, we integrate 4D label-free quantitative proteomics, a nanomixing-enhanced microfluidic surface-enhanced Raman spectroscopy (SERS) platform, and machine learning to sensitively identify and validate blood protein biomarkers associated with MPP⁺ LUAD. Comparative proteomics reveal 44 differentially expressed proteins (DEPs) between MPP⁺ and MPP⁻ LUADs, with bioinformatics uncovering their roles in MPP⁺ LUAD formation. To enable sensitive, multiplex detection of 4 upregulated DEPs, the nanomixing effect is leveraged to enhance target protein-SERS barcode interactions while minimizing nonspecific binding to antibody-functionalized gold electrodes. The SERS barcode cocktail allows simultaneous detection of the 4 selected DEPs. Machine learning models based on SERS detection effectively distinguish MPP⁺ from MPP⁻ LUAD patients, as well as LUAD patients from healthy donors. This approach demonstrates strong diagnostic potential for early, non-invasive MPP detection in LUAD, advancing nanotechnology-driven disease diagnosis and monitoring.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224922PMC
http://dx.doi.org/10.1002/advs.202501336DOI Listing

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