Phenomics. 2026 May 20;6(3):213-229. doi: 10.1007/s43657-026-00322-4. eCollection 2026 Jun.

ABSTRACT

Early cancer detection remains challenging due to the lack of reliable pan-cancer screening methods, particularly blood-based biomarkers. Using a novel three-tiered validation framework combining artificial intelligence (AI)-powered literature mining of 180,000 PubMed articles (1950-2024), multiomics integration across major databases, and extensive clinical validation, we identified macrophage migration inhibitory factor (MIF) as a promising blood-based biomarker for pan-cancer detection. Multiomics analysis revealed consistent MIF upregulation across 21 cancer types at the transcriptional level and across 12 cancer types at the protein level. Clinical validation in independent cohorts (n = 4,269) showed that serum MIF protein levels discriminated effectively between cancer patients and healthy controls (median AUC = 0.994) and between cancer and benign conditions (median AUC = 0.881). Notably, comparative analyses showed that MIF demonstrated superior or comparable performance to established cancer-specific markers, including AFP for hepatocellular carcinoma (MIF AUC = 0.885 vs. AFP AUC: 0.744-0.887) and CA125 for ovarian cancer (MIF AUC = 0.831 vs. CA125 AUC: 0.58-0.71). Meta-analysis of 28 cohorts (n = 5,347) confirmed the diagnostic efficacy of MIF (pooled AUC: 0.782). This cost-effective, blood-based ELISA approach establishes MIF as a valuable tool for broad applications in cancer screening.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s43657-026-00322-4.

PMID:42750739 | PMC:PMC13578188 | DOI:10.1007/s43657-026-00322-4

Discov Oncol. 2026 Aug 1;17(1):1333. doi: 10.1007/s12672-026-05700-y.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) remains biologically heterogeneous, and molecular states linking tumor-cell intrinsic programs with post-translational regulation, immune contexture and drug-specific vulnerability remain incompletely defined. ZDHHC16 is a DHHC-family palmitoyl acyltransferase, but its clinical relevance and biological context in HCC remain unclear.

METHODS: Public transcriptomic, clinical, single-cell, proteomic, palmitoylome, immune-related and pharmacogenomic datasets were integrated to characterize ZDHHC16 in HCC. ZDHHC16 expression, exploratory survival separation, cellular localization, pathway activity, palmitoylation-associated candidates, immune microenvironment features and predicted drug response were evaluated. siRNA-mediated knockdown, MTT assays and colony formation assays were performed in HepG2 and Huh7 cells.

RESULTS: ZDHHC16 was upregulated in HCC. In exploratory Kaplan-Meier analyses restricted to primary tumors and using endpoint-specific data-derived cutoffs, the curves showed expression-group separation for overall survival, disease-free interval and progression-free interval (unadjusted log-rank P = 0.019, 0.019 and 0.011, respectively). These analyses were not adjusted for clinical covariates and do not establish independent prognostic value. Single-cell analysis localized ZDHHC16 mainly to malignant epithelial-related compartments. ZDHHC16 knockdown reduced MTT-based cell viability and clonogenic growth in HepG2 and Huh7 cells. ZDHHC16-high tumors were enriched for cell-cycle progression, DNA replication, DNA repair, RNA processing, ubiquitin-mediated proteolysis and proteasome-related programs. After deduplication at the gene-symbol level, palmitoylome-guided integration nominated 28 transcriptionally correlated palmitoylation-associated candidates, including EZH2, PI4K2A and ZDHHC6; the screen did not establish direct ZDHHC16 substrates. ZDHHC16-high tumors also showed immune-remodeled features and drug-specific predicted IC50 patterns.

CONCLUSIONS: Integrated data support ZDHHC16 as a marker of a malignant epithelial, growth-associated HCC state accompanied by palmitoylation- and proteostasis-related programs, altered immune contexture and drug-specific predicted IC50 patterns. Direct ZDHHC16-dependent palmitoylation, independent prognostic value and therapeutic utility require biochemical and prospective clinical validation.

PMID:42742876 | PMC:PMC13578202 | DOI:10.1007/s12672-026-05700-y