Mol Cancer. 2025 Dec 2. doi: 10.1186/s12943-025-02514-4. Online ahead of print.

ABSTRACT

BACKGROUND: Greater understanding of differential therapeutic sensitivity, specifically to immunotherapy, in small-cell lung cancer (SCLC) is required.

METHODS: We explored SCLC heterogeneity through integrated molecular characterization of tumor tissue samples from 159 treatment-naive patients, utilizing genetic, epigenetic, transcriptional, and proteomic profiling, immunohistochemistry staining for multiple biologically relevant markers including transcriptional subtype-defining proteins, and spatial immune profiling using multiplex immunofluorescence.

RESULTS: Multi-omics analysis confirmed high heterogeneity across/within neuroendocrine and non-neuroendocrine subtypes. Methylomics analysis identified four methylome clusters that may enhance subtype prediction, prognosis, and longitudinal monitoring of subtype evolution. Immunohistochemistry analysis showed high MHC-I expression in non-neuroendocrine subtypes, which have greatest potential benefit from adding immunotherapy to chemotherapy; high DLL3 expression associated with neuroendocrine subtypes and an immune-cold tumor microenvironment. Multiplex immunofluorescence demonstrated associations of MHC-I with spatial arrangement and phenotypic features of immune cells in the tumor microenvironment of high-MHC-I-expressing SCLC, providing mechanistic rationale for MHC-I as a potential biomarker of immunotherapy response.

CONCLUSIONS: This multimodal profiling analysis provides further insights into the biologic complexity of SCLC and highlights potential therapeutic vulnerabilities of distinct disease subtypes.

PMID:41331472 | DOI:10.1186/s12943-025-02514-4

Annu Int Conf IEEE Eng Med Biol Soc. 2025 Jul;2025:1-7. doi: 10.1109/EMBC58623.2025.11254134.

ABSTRACT

The complexity of biological systems and the limitations of analyzing individual omics studies for biomarker discovery have raised the need for a holistic approach by multi-omics integration. By integrating data from multiple layers, researchers can gain insights into the entire system rather than just individual components. Also, integrative analysis can help identify molecular signatures that are more accurate in predicting disease onset, progression, and response to treatment, leading to better-targeted therapies and personalized medicine. In this paper, we explored statistical and deep learning methods for integrative analysis of metabolomics, lipidomics, peptidomics, proteomics, and glycoproteomics data acquired by LC-MS/MS analysis of serum samples from 20 hepatocellular carcinoma (HCC) cases and 20 patients with liver cirrhosis (CIRR). The goal is to identify a panel of multi-omics features that distinguish HCC cases from cirrhotic controls. A pathway analysis using these features identified biological pathways such as LXR/RXR Activation and Acute Response signaling as significantly enriched in our multi-omics datasets.

PMID:41336317 | PMC:PMC12694951 | DOI:10.1109/EMBC58623.2025.11254134