ABSTRACT
Background and Aim: There are several existing systemic 1st- line therapies for advanced hepatocellular carcinoma (HCC), including atezolizumab/bevacizumab (Atez/Bev), sorafenib and lenvatinib. This study aims to compare the effectiveness of these three 1st-line systemic treatments in a real-world setting for HCC, focusing on specific patient subgroups analysis. Methods: A total of 177 patients with advanced HCC treated with Atez/Bev (n = 38), lenvatinib (n = 21) or sorafenib (n = 118) as 1st line systemic therapy were retrospectively analyzed and compared. Primary endpoints included objective response rate (ORR), progression-free survival (PFS) and 15-month overall survival (15-mo OS). Subgroups regarding liver function, etiology, previous therapy and toxicity were analyzed. Results: Atez/Bev demonstrated significantly longer median 15-month OS with 15.03 months compared to sorafenib with 9.43 months (p = 0.04) and lenvatinib with 8.93 months (p = 0.05). Similarly, it had highest ORR of 31.6% and longest median PFS with 7.97 months, independent of etiology. However, significantly superiority was observed only compared to sorafenib (ORR: 4.2% (p < 0.001); PFS: 4.57 months (p = 0.03)), but not comparing to lenvatinib (ORR: 28.6% (p = 0.87); PFS: 3.77 months (p = 0.10)). Atez/Bev also resulted in the longest PFS in patients with Child-Pugh A and ALBI 1 score and interestingly in those previously treated with SIRT. Contrary, sorafenib was non inferior in patients with impaired liver function. Conclusion: Atez/Bev achieved longest median PFS and 15-mo OS independent of etiology and particularly in patients with stable liver function or prior SIRT treatment. Regarding therapy response lenvatinib was non-inferior to Atez/Bev. Finally, sorafenib seemed to perform best for patients with deteriorated liver function.
Subject(s)
Alopecia/genetics , Gene Expression Profiling/methods , Genetic Predisposition to Disease , Hair Follicle/metabolism , Receptors, Androgen/genetics , Adult , Alopecia/metabolism , Alopecia/pathology , Genetic Loci , Hair Follicle/pathology , Humans , Male , Receptors, Androgen/metabolism , Young AdultABSTRACT
Male-pattern baldness (MPB) is a common and highly heritable trait characterized by androgen-dependent, progressive hair loss from the scalp. Here, we carry out the largest GWAS meta-analysis of MPB to date, comprising 10,846 early-onset cases and 11,672 controls from eight independent cohorts. We identify 63 MPB-associated loci (P<5 × 10-8, METAL) of which 23 have not been reported previously. The 63 loci explain â¼39% of the phenotypic variance in MPB and highlight several plausible candidate genes (FGF5, IRF4, DKK2) and pathways (melatonin signalling, adipogenesis) that are likely to be implicated in the key-pathophysiological features of MPB and may represent promising targets for the development of novel therapeutic options. The data provide molecular evidence that rather than being an isolated trait, MPB shares a substantial biological basis with numerous other human phenotypes and may deserve evaluation as an early prognostic marker, for example, for prostate cancer, sudden cardiac arrest and neurodegenerative disorders.
Subject(s)
Alopecia/genetics , 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics , Adipogenesis/genetics , Case-Control Studies , Fibroblast Growth Factor 5/genetics , Genetic Association Studies , Genome-Wide Association Study , Genotype , Humans , Intercellular Signaling Peptides and Proteins/genetics , Interferon Regulatory Factors/genetics , Male , Melatonin , Membrane Proteins/genetics , Phenotype , Signal Transduction/genetics , Trans-Activators/geneticsABSTRACT
BACKGROUND: Human hair follicle (HF) cycling is characterised by the tight orchestration and regulation of signalling cascades. Research shows that micro(mi)RNAs are potent regulators of these pathways. However, knowledge of the expression of miRNAs and their target genes and pathways in the human HF is limited. The objective of this study was to improve understanding of the role of miRNAs and their regulatory interactions in the human HF. METHODS: Expression levels of ten candidate miRNAs with reported functions in hair biology were assessed in HFs from 25 healthy male donors. MiRNA expression levels were correlated with mRNA-expression levels from the same samples. Identified target genes were tested for enrichment in biological pathways and accumulation in protein-protein interaction (PPI) networks. RESULTS: Expression in the human HF was confirmed for seven of the ten candidate miRNAs, and numerous target genes for miR-24, miR-31, and miR-106a were identified. While the latter include several genes with known functions in hair biology (e.g., ITGB1, SOX9), the majority have not been previously implicated (e.g., PHF1). Target genes were enriched in pathways of interest to hair biology, such as integrin and GnRH signalling, and the respective gene products showed accumulation in PPIs. CONCLUSIONS: Further investigation of miRNA expression in the human HF, and the identification of novel miRNA target genes and pathways via the systematic integration of miRNA and mRNA expression data, may facilitate the delineation of tissue-specific regulatory interactions, and improve our understanding of both normal hair growth and the pathobiology of hair loss disorders.
