Transl Cancer Res. 2025 Sep 30;14(9):6102-6117. doi: 10.21037/tcr-2025-1092. Epub 2025 Sep 26.

ABSTRACT

BACKGROUND AND OBJECTIVE: Lung adenocarcinoma (LUAD), as the main subtype of non-small cell lung cancer (NSCLC), faces clinical challenges including molecular heterogeneity, late diagnosis, and aggressive growth, leading to a low 5-year survival rate. Biomarkers are critical for early detection, accurate differentiation of benign/malignant lesions, and guiding personalized treatment strategies. Proteomic technologies using liquid biopsy show potential by analyzing protein changes and post-translational modifications (PTMs) to identify novel biomarkers and unravel cancer mechanisms. This review examines proteomic advances in LUAD, compares platform strengths, lists validated protein markers, and discusses challenges like specificity and regulations. It aims to develop a precision medicine framework by integrating multi-omics data for improved diagnosis and treatment.

METHODS: This study conducted a literature review by searching the PubMed and Web of Science databases for original articles written in English from 2002 to 2025, using the keywords "lung adenocarcinoma" OR "LUAD" AND "biomarkers" AND "proteomics" OR "SomaScan" OR "spatial proteomics" to identify the latest research findings in the field of proteomics technology and LUAD biomarkers. The included studies mainly focused on the current landscape of biomarkers in the diagnosis, treatment, and prognosis of LUAD.

KEY CONTENT AND FINDINGS: This review discusses high-throughput methods for comprehensive protein profiling in accessible biospecimens (tissues, blood, urine) to identify biomarkers for LUAD. We systematically evaluate emerging proteomic strategies, including mass spectrometry (MS), proximity extension assays (PEAs), spatial proteomics techniques, and SomaScan platforms-coupled with innovative computational frameworks have revolutionized biomarkers discovery and their translational potential in developing precision diagnostics and targeted therapies. Additionally, the review addresses challenges in integrating proteomics with genomics, transcriptomics, and metabolomics, offering new methodologies and expanding research in life sciences. As technological advancements continue, it is anticipated that more potential biomarkers will be conducted to validate the broader application in LUAD treatment, addressing early-stage disease complexities and aiding in selecting more effective treatment strategies.

CONCLUSIONS: By synthesizing cutting-edge evidence on proteome-driven LUAD biomarkers, this review elucidates actionable strategies to refine early detection protocols and mechanism-informed personalized treatment frameworks, directly advancing precision oncology initiatives for this prevalent malignancy through biomarker-guided clinical decision-making and multi-omics integration.

PMID:41158224 | PMC:PMC12554480 | DOI:10.21037/tcr-2025-1092

Cancer Cell. 2025 Feb 14:S1535-6108(25)00030-3. doi: 10.1016/j.ccell.2025.01.012. Online ahead of print.

ABSTRACT

Recent advances have shed light on the molecular heterogeneity of small cell lung cancer (SCLC), yet the spatial organizations and cellular interactions in tumor immune microenvironment remain to be elucidated. Here, we employ co-detection by indexing (CODEX) and multi-omics profiling to delineate the spatial landscape for 165 SCLC patients, generating 267 high-dimensional images encompassing over 9.3 million cells. Integrating CODEX and genomic data reveals a multi-positive tumor cell neighborhood within ASCL1⁺ (SCLC-A) subtype, characterized by high SLFN11 expression and associated with poor prognosis. We further develop a cell colony detection algorithm (ColonyMap) and reveal a spatially assembled immune niche consisting of antitumoral macrophages, CD8⁺ T cells and natural killer T cells (MT²) which highly correlates with superior survival and predicts improving immunotherapy response in an independent cohort. This study serves as a valuable resource to study SCLC spatial heterogeneity and offers insights into potential patient stratification and personalized treatments.

PMID:39983726 | DOI:10.1016/j.ccell.2025.01.012