J Transl Med. 2025 May 2;23(1):504. doi: 10.1186/s12967-025-06517-z.

ABSTRACT

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS), particularly perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), are synthetic chemicals known for their widespread use and environmental persistence. These compounds have been increasingly linked to hepatotoxicity and the development of hepatocellular carcinoma (HCC). However, the molecular mechanisms by which PFAS contribute to HCC remain underexplored.

METHODS: This study employs a multi-omics approach that combines network toxicology, integrated machine learning, single-cell RNA sequencing, spatial transcriptomics, experimental validation, and molecular docking simulations to uncover the mechanisms through which PFAS exposure drives HCC. We analyzed publicly available transcriptomic data from several HCC cohorts and used differential gene expression analysis to identify targets associated with both PFAS exposure and HCC. We constructed a protein-protein interaction (PPI) network and a survival risk model, the PFAS-related HCC signature (PFASRHSig), based on integrated machine learning to identify prognostic biomarkers, with the goal of identifying core targets of PFAS in HCC progression and prognosis. RT-qPCR and immunohistochemical (IHC) staining were used to validate the expression levels of the targets in both tumor and normal tissues. Molecular docking simulations were conducted to assess the binding affinities between PFAS compounds and selected target proteins.

RESULTS: Functional enrichment studies revealed that PFAS targets were associated with metabolic signaling pathways, which are actively involved in lipid, glucose, drug metabolism, etc. Through integrated machine learning and PPI network analysis, we identified six genes, APOA1, ESR1, IGF1, PPARGC1A, SERPINE1, and PON1, that serve as core targets of PFAS in both HCC progression and prognosis. These targets were further validated via bulk RNA-seq, single-cell RNA-seq, and spatial transcriptomics, which revealed differential expression patterns across various cell types in the HCC tumor microenvironment. The results of RT-qPCR and IHC staining were consistent with the in silico findings. Molecular docking simulations revealed strong binding affinities between PFAS compounds and these core targets, supporting their potential roles in PFAS-induced hepatocarcinogenesis.

CONCLUSIONS: Our study highlights key molecular targets and pathways involved in PFAS-induced liver carcinogenesis and proposes a robust survival risk model (PFASRHSig) for HCC. These findings provide new insights into PFAS toxicity mechanisms and offer potential therapeutic targets for mitigating the health risks associated with PFAS exposure. Collectively, our findings help in advancing clinical applications by providing insights into disease mechanisms and potential therapeutic interventions.

PMID:40317014 | PMC:PMC12049027 | DOI:10.1186/s12967-025-06517-z

Ann Med. 2025 Dec;57(1):2494671. doi: 10.1080/07853890.2025.2494671. Epub 2025 May 3.

ABSTRACT

BACKGROUND: The combination of traditional Chinese medicine (TCM) with chemotherapy has been widely applied in the treatment of gastric cancer (GC). However, previous clinical studies have been constrained by small sample sizes and a lack of investigation into the molecular mechanisms of TCM. This study aims to assess the efficacy of TCM in treating GC by leveraging the strengths of meta-analysis and multi-omics approaches while also summarizing the underlying pharmacological mechanisms.

METHODS: A systematic literature review and meta-analysis were conducted using online databases to collect data before May 2024. This was to investigate the association between TCM combined with chemotherapy and the prognosis in GC. The molecular targets between the high-frequency TCMs and GC were identified through network pharmacology. The underlying mechanisms were investigated using multi-omics.

RESULTS: 9 studies with 2,158 patients were included. The meta-analysis results demonstrated that the combination of TCM and chemotherapy significantly improved the overall survival (OS) of GC patients (OR = 2.91; 95% CI: 2.70-3.12, p < 0.00001) and enhanced their quality of life (OR = 4.00; 95% CI: 1.99-8.03, p < 0.0001). Network pharmacology analysis identified 13 potential molecular targets of TCM in GC; additionally, multi-omics analysis highlighted the significant roles of MK, MIF, GALECTIN, and CypA signaling pathways in GC.

CONCLUSION: The combination of TCM with chemotherapy significantly improves the prognosis of GC; future research can focus on these key molecular targets and signaling pathways. This supports the application of precision medicine in cancer treatment and suggests the rational use of TCM in managing GC.

PMID:40317214 | PMC:PMC12051567 | DOI:10.1080/07853890.2025.2494671

Expert Rev Mol Diagn. 2025 Jun;25(6):263-274. doi: 10.1080/14737159.2025.2498545. Epub 2025 Apr 28.

ABSTRACT

INTRODUCTION: In recent years, circulating tumor DNA (ctDNA) has emerged as a promising method for detection of minimal or molecular residual disease (MRD) among patients with breast cancer.

AREAS COVERED: In this narrative review, we provide a summary of currently available studies assessing use of ctDNA in detection of MRD in patients after completion of curative therapy. Additionally, we discuss limitations of present studies, future considerations, and an overview of ongoing trials evaluating the clinical utility of MRD-directed therapy interventions.

EXPERT OPINION: While the clinical utility of MRD-directed therapy guidance remains under investigation, collective data from studies overwhelmingly confirm the prognostic value of ctDNA status across various stages and subtypes of breast cancer. Results from ongoing clinical trials in the coming years will provide more clarity on the overall clinical benefit of MRD-directed interventions for breast cancer patients.

PMID:40288891 | DOI:10.1080/14737159.2025.2498545