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

Cancer Treat Rev. 2025 Jun 14;139:102979. doi: 10.1016/j.ctrv.2025.102979. Online ahead of print.

ABSTRACT

Breast cancer is characterized by significant molecular heterogeneity; therefore, there are distinct clinical features, treatment modalities, and prognostic outcomes across its various molecular subtypes. In the era of precision medicine, liquid biopsy has emerged as a convenient and minimally invasive technique capable of dynamically representing the comprehensive tumor gene spectrum. This review systematically elaborates the clinical value of liquid biopsy as a breakthrough tool for precision diagnosis and treatment in breast cancer through dynamic detection of key biomarkers, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, and non-coding RNA (ncRNA). Specific genetic mutations and methylation signatures in ctDNA can be applied to early breast cancer screening, minimal residual disease monitoring, and tracking drug resistance mechanisms. CTCs enumeration (≥1/7.5 mL in early-stage cancer or ≥ 5/7.5 mL in metastatic cancer) and PD-L1 expression levels demonstrate direct correlations with prognostic stratification and the efficacy of immunotherapy. As the specificity and sensitivity of liquid biopsy continue to improve, personalized treatment strategies, informed by biomarker analysis and targeted precision therapies, have unveiled new avenues of hope for patients with breast cancer. However, several challenges persist in the practical application of liquid biopsy. Despite persistent challenges, such as insufficient standardization and difficulties in resolving low-abundance variants, future advancements should focus on multi-omics integration and AI-driven technological breakthroughs to overcome bottlenecks in clinical translation. This review summarizes cutting-edge liquid biopsy technologies for identifying clinically significant molecular biomarkers, focusing on discussing critical challenges in the strategies to advance precision oncology applications for optimized treatment guidance and disease surveillance in breast cancer.

PMID:40540857 | DOI:10.1016/j.ctrv.2025.102979