Innovation (Camb). 2025 Aug 6;7(1):101076. doi: 10.1016/j.xinn.2025.101076. eCollection 2026 Jan 5.

ABSTRACT

Although circulating cell-free DNA (cfDNA) methylation has emerged as the mainstream approach in multi-cancer detection blood tests (MCDBTs), the potential of integrating proteins and mutations, to enhance its performance remains unclear. The PROMISE study (NCT04972201) was conducted to investigate the feasibility of a multi-omics integration strategy in MCDBTs across nine types of cancers in head and neck (excluding nasopharynx), esophagus, lung, stomach, liver, biliary tract, pancreas, colorectum, and ovary. Blood samples were prospectively collected from 1,706 participants (840 non-cancer; 866 cancer) and then randomly divided into training and validation sets. The complementarity between various omics were investigated, and specific omics features were carefully selected for further multimodal model construction. The methylation-based classifier outperformed both the mutation-based and protein-based classifiers. As 95.0% of cancer cases detected by the mutation-based classifier were simultaneously identified by the methylation-based classifier, while 14.0% of the protein-positive samples were missed, protein markers may provide complementary value to the methylation-based classifier. Compared with the methylation-based classifier, the multimodal classifier combining methylation and protein features exhibited an improved sensitivity of 75.1% (95% confidence interval [CI], 69.3%-80.3%) at the same specificity of 98.8% with the accuracy of top predicted origin (TPO1) of 73.1% (95% CI, 66.2%-79.2%). Notably, the TPO1 accuracy reached 100% in liver and ovarian cancers with negative results of the methylation-based classifier. Collectively, these data suggest that the integration of protein markers in the multimodal classifier can offer additional benefits to the methylation-based classifier, particularly in identifying liver and ovarian cancers.

PMID:41737326 | PMC:PMC12925926 | DOI:10.1016/j.xinn.2025.101076

Int J Surg. 2025 Jul 15. doi: 10.1097/JS9.0000000000003049. Online ahead of print.

ABSTRACT

Fatty acid-binding proteins (FABPs) are intracellular lipid chaperones with molecular weights of approximately 14-15 kDa. By binding and transporting fatty acids and lipid-related molecules, FABPs precisely regulate metabolic pathways, signal transduction, and gene expression, playing a central role in cancer initiation and progression. The 11 identified subtypes (FABP1-FABP12; FABP11 is identical to FABP3) exhibit tissue-specific expression and influence tumor progression through metabolic reprogramming, immune microenvironment modulation, and therapy resistance. Metabolically, FABPs enhance fatty acid uptake, β-oxidation, and synthesis, meeting the high proliferative demands of tumors. In immune regulation, FABP4+ macrophages secrete IL-6 to suppress T cell activity, while FABP6 downregulates MHC-I molecule expression to reduce CD8+ T cell infiltration, fostering an immunosuppressive microenvironment. Regarding therapy resistance, FABP4 enhances mitochondrial β-oxidation to reduce apoptosis in ovarian cancer, and FABP5 promotes chemoresistance in HCC via the HIF-1α pathway. Functional heterogeneity exists among subtypes: FABP7 drives glioblastoma stem cell migration via RXRα signaling, while FABP5 exhibits context-dependent roles, promoting HCC progression but suppressing colorectal cancer (CRC) through mTOR-mediated autophagy. Clinically, FABPs serve as diagnostic biomarkers and therapeutic targets. However, challenges such as insufficient target specificity, cross-cancer heterogeneity, and normal tissue toxicity remain. Future studies should integrate multi-omics and single-cell technologies to elucidate cell-specific mechanisms and develop precise combination therapies for clinical translation.

PMID:40717587 | DOI:10.1097/JS9.0000000000003049