Biomedicines. 2025 Sep 11;13(9):2238. doi: 10.3390/biomedicines13092238.

ABSTRACT

Background:HTR1F (5-Hydroxytryptamine Receptor 1F) encodes a G protein-coupled receptor involved in serotonin signaling. Although dysregulated HTR1F expression has been implicated in certain malignancies, its biological functions and clinical significance across cancer types remain largely unexplored. Methods: We performed an integrative pan-cancer analysis of transcriptomic and pharmacogenomic datasets covering 34 cancer types (PAN-CAN cohort, N = 19,131; normal tissues, G = 60,499). Drug sensitivity and molecular docking analyses were conducted using the GSCALite database. The protein-protein interaction (PPI) network of HTR1F was constructed via the STRING database. Additionally, we evaluated the effects of HTR1F overexpression on proliferation and invasion in human lung squamous cell carcinoma (LUSC) cell lines NCI-H520 and NCI-H226. Results:HTR1F expression was significantly upregulated in 17 cancer types and was associated with poor prognosis, with LUSC showing an AUC of 0.912 for 1-year survival prediction. In LUSC, 695 genes were upregulated and 67 downregulated in response to HTR1F overexpression. HTR1F expression correlated with immune-related genes, immune checkpoints, tumor-infiltrating immune cells, tumor mutation burden (TMB), microsatellite instability (MSI), and drug responses. Genomic alterations, including amplification and deletion, were positively associated with HTR1F expression. Drug sensitivity analysis identified compounds such as sotrastaurin (-10.2 kcal/mol), austocystin D (-9.7 kcal/mol), and tivozanib (-9.3 kcal/mol) as potentially effective inhibitors based on predicted binding affinity. Functional enrichment analyses (GO, KEGG) and GSEA revealed that HTR1F is primarily involved in cell cycle regulation, DNA replication, cellular senescence, and immune-related pathways. Functional validation showed that HTR1F overexpression promotes proliferation of LUSC cells via the MAPK signaling pathway. Conclusions: Our integrative analysis highlights HTR1F as a potential biomarker associated with prognosis, immune modulation, and drug sensitivity across multiple cancer types. These findings provide a foundation for future experimental and clinical studies to explore HTR1F-targeted therapies.

PMID:41007799 | PMC:PMC12467612 | DOI:10.3390/biomedicines13092238

bioRxiv [Preprint]. 2025 Sep 17:2025.09.12.675904. doi: 10.1101/2025.09.12.675904.

ABSTRACT

Spatial 'omics technologies are a powerful tool for mapping the relationship between cellular organization and molecular distributions in healthy and diseased tissue microenvironments. Here, we describe a novel multimodal pipeline that represents experimental and computational advances for spatiomolecular analysis of tissue samples across molecular classes. This adaptable method integrates matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) lipidomics, spatial transcriptomics (ST), multiplexed immunofluorescence microscopy (MxIF), and histopathological staining to uncover spatiomolecular profiles associated with unique cellular niches and pathological features. We demonstrate the power of this approach using two different complex human disease systems: Alzheimer's disease in human brain tissue and type 2 diabetes mellitus in the human pancreas. By identifying molecular markers associated with disease pathology in the pancreas and brain, we shed light on biologically significant pathways that are impacted in these two spatially complex diseases and highlight the powerful potential of accurate, high-resolution multimodal integration approaches.

PMID:41000710 | PMC:PMC12458195 | DOI:10.1101/2025.09.12.675904

Nat Commun. 2025 Sep 25;16(1):8388. doi: 10.1038/s41467-025-63050-9.

ABSTRACT

Spatial technologies examining the cell and tissue microenvironment at near single-cell resolution are revealing important molecular insights. However, few tools enable integrated, interactive analysis of spatial-omics with tissue morphology in the same functional tissue unit. Here, we present FUSION (Functional Unit State Identification in Whole Slide Images), a web-based platform for visualizing and analyzing spatial-omics data with high-resolution histology. FUSION provides workflows for assessing cell compositions, quantitative morphometrics, and comparative tissue analyses. We demonstrate applicability across spatial assays, including 10x Visium, Visium HD, 10x Xenium, Cell DIVE, and PhenoCycler, applied to healthy and diseased tissues from kidney, small intestine, lung, and skin in the Human BioMolecular Atlas Program. FUSION is cloud-based, open-source, and accessible at https://fusion.hubmapconsortium.org/ , hosting over 50 paired datasets and tutorials. In a series of use cases, we show its capacity to distinguish renal glomeruli injury states, quantify morphometric changes, and characterize fibrosis with immune infiltration.

PMID:40998789 | PMC:PMC12462499 | DOI:10.1038/s41467-025-63050-9

Sci Prog. 2025 Jul-Sep;108(3):368504251383055. doi: 10.1177/00368504251383055. Epub 2025 Sep 24.

ABSTRACT

ObjectiveTo synthesize recent molecular advances that inform diagnosis, risk-stratification, and perioperative treatment in early-stage and locally advanced non-small cell lung carcinoma (NSCLC), with emphasis on comprehensive genomic profiling, minimal residual disease (MRD) detection by circulating tumor DNA (ctDNA), and the translation of biomarkers into targeted and immunotherapy strategies.MethodsSystematic review registered in PROSPERO (CRD420251076423). Searches of PubMed, Scopus, Web of Science, and Embase (January 2015-April 2025) followed PRISMA 2020/PRISMA-S. From 4640 records, 890 duplicates were removed; 3750 titles/abstracts were screened; 150 full texts were assessed; 75 studies met inclusion criteria. Risk of bias used Newcastle-Ottawa Scale (NOS) for observational studies and Cochrane RoB 2 tool for randomized controlled trials; certainty was summarized with GRADE where applicable.ResultsActionable alterations (e.g. EGFR, ALK, KRAS, MET, RET, BRAF, NTRK) are prevalent in early-stage NSCLC and comparable to advanced disease, supporting routine comprehensive genomic profiling in curative-intent settings. Next-generation sequencing (NGS) and ctDNA enable the detection of MRD, earlier relapse prediction, and dynamic treatment monitoring. Perioperative strategies integrating targeted therapy and immunotherapy (e.g. adjuvant EGFR-TKI, neoadjuvant chemo-immunotherapy) improve pathological and disease-free outcomes in selected biomarker-defined populations. Evidence profiles generally show low-to-moderate risk of bias and moderate-to-high certainty for key outcomes related to profiling and MRD, with heterogeneity across platforms and endpoints.ConclusionsMolecular advances-particularly broad NGS and ctDNA-based MRD-are reshaping the perioperative management of early and locally advanced NSCLC, enabling precision selection for targeted and immunotherapy approaches. Standardization of testing workflows and reporting, and cost-effective implementation are priorities for equitable adoption and for future trials that combine NGS, MRD, and multi-omic/AI-driven risk stratification.

PMID:40990633 | PMC:PMC12461064 | DOI:10.1177/00368504251383055