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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://dx.doi.org/10.1002/advs.202501336 | DOI Listing |
Br J Cancer
September 2025
Department of Genetics, Institut Curie, PSL Research University, Paris, France.
Background: Identifying molecular alterations specific to advanced lung adenocarcinomas could provide insights into tumour progression and dissemination mechanisms.
Method: We analysed tumour samples, either from locoregional lesions or distant metastases, from patients with advanced lung adenocarcinoma from the SAFIR02-Lung trial by targeted sequencing of 45 cancer genes and comparative genomic hybridisation array and compared them to early tumours samples from The Cancer Genome Atlas.
Results: Differences in copy-number alterations frequencies suggest the involvement in tumour progression of LAMB3, TNN/KIAA0040/TNR, KRAS, DAB2, MYC, EPHA3 and VIPR2, and in metastatic dissemination of AREG, ZNF503, PAX8, MMP13, JAM3, and MTURN.
J Thorac Oncol
September 2025
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; Emeritus Professor, Seoul National University College of Medicine, Seoul, Republic of Korea.
Introduction: Multifocal subsolid nodules (SSNs) are increasingly detected with widespread lung cancer screening and advanced thoracic imaging, representing a spectrum of multifocal lung adenocarcinomas (LUADs). When synchronous SSNs coexist with a surgically confirmed subsolid LUAD, their trajectories remain poorly understood, contributing to uncertainty regarding optimal management strategies. This study aimed to evaluate the clinical course and impact of synchronous SSNs in such patients and to identify features associated with their progression.
View Article and Find Full Text PDFDev Cell
September 2025
Department of Clinical Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; Faculty of Medical Laborat
Cytokines link inflammation to tumorigenesis, but the role of post-translational modifications in regulating their function within the extra-tumoral environment remains poorly defined. Here, we identify tumor-derived tumor necrosis factor (TNF) receptor superfamily member 11B (TR11B) as a key driver of lung adenocarcinoma (LUAD) progression and therapeutic resistance. Mechanistically, O-GlcNAc transferase (OGT)-mediated O-GlcNAcylation at serine 151 stabilizes TR11B and facilitates its interaction with the membrane protein EPS15 homology domain-containing protein 1 (EHD1), promoting cyclin dependent kinase 2 (CDK2) phosphorylation and cell cycle progression.
View Article and Find Full Text PDFGenes Genomics
September 2025
Department of Clinical Laboratory, The First Affiliated Hospital of Guilin Medical University, Le Qun Road 15, Guilin, 541001, Guangxi, China.
Background: Lung cancer (LC) is the leading cause of cancer-related deaths globally. Genetic variants in mismatch repair (MMR) genes, such as MutS homolog 2 (MSH2), MutS homolog 6 (MSH6) and MutL homolog 1 (MLH1), may influence individual susceptibility and clinical outcomes in LC.
Objective: This study investigated the associations of genetic polymorphisms in MSH2, MSH6, and MLH1 with susceptibility and survival outcomes in lung cancer patients in the Guangxi Zhuang population.
Mol Cell Biochem
September 2025
Department of Laboratory Medicine, The People's Hospital of Zhongjiang, No. 96, Dabei Street, Kaijiang Town, Zhongjiang County, Deyang City, 618100, Sichuan Province, China.
5-methylcytosine (m5C) methylation is a post-transcriptional modification of RNAs, and its dysregulation plays pro-tumorigenic roles in lung adenocarcinoma (LUAD). Here, this study elucidated the mechanism of action of NSUN2, a major m5C methyltransferase, on LUAD progression. mRNA expression was analyzed by quantitative PCR.
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