Hum Mutat. 2026 May 21;2026:6434376. doi: 10.1155/humu/6434376. eCollection 2026.

ABSTRACT

Immune checkpoint inhibitors have become integral to the management of non-small cell lung cancer (NSCLC), yet both primary and acquired resistance remain frequent and are only partially captured by routine biomarkers such as programmed death-ligand 1 (PD-L1) immunohistochemistry and tumor mutational burden (TMB). Resistance is increasingly viewed as a multiaxis functional phenotype shaped by antigenicity and neoantigen quality, antigen processing and presentation competence, interferon signaling and adaptive resistance programs, tumor-immune spatial organization, suppressive myeloid/stromal ecosystems, and metabolic constraints that limit effector function. Multiomics profiling provides a practical route to translate genomic event anchors into reproducible, mechanistically interpretable biomarker outputs by assembling coherent evidence chains across genomics, transcriptomics, epigenomics, proteomics, and metabolomics, complemented by spatial assays, digital pathology, and imaging-derived surrogates.

PMID:42181742 | PMC:PMC13191777 | DOI:10.1155/humu/6434376

Probiotics Antimicrob Proteins. 2026 May 23. doi: 10.1007/s12602-026-11062-2. Online ahead of print.

ABSTRACT

Autoimmune hepatitis (AIH) is a chronic progressive inflammatory liver disease with a rising global incidence. The treatment of AIH remains challenging because first-line drugs show limited efficacy and systemic side effects. Gut microbiota plays a crucial role in the pathogenesis of AIH, leading to growing interest in developing probiotic-based therapies. In this study, we used multi-omics analysis to investigate the therapeutic effects of a quadruple probiotic mixture (Probiotic-quad) consisting of Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis, and Bacillus cereus in a well-established chronic AIH murine model. Our results showed that Probiotic-quad treatment significantly alleviated AIH progression, as evidenced by lower serum liver enzyme levels, ameliorated hepatic inflammatory infiltration and histopathological damage. Metagenomic sequencing results showed that gut dysbiosis in AIH mice was partially reversed after Probiotic-quad administration. Additionally, the integrity of the intestinal epithelial barrier was restored, accompanied by a reduction in serum lipopolysaccharide levels. Untargeted metabolomic and transcriptomic analysis revealed that Probiotic-quad treatment was linked to alterations in hepatic metabolism, including the citrate cycle and tryptophan metabolism, and was associated with reduced activation of the NF-κB and NOD-like receptor signaling pathways. These findings suggest that Probiotic-quad treatment ameliorates AIH severity and is potentially associated with changes in hepatic immune responses, metabolism, gut microbiota, and intestinal barrier function, highlighting its potential as an adjuvant therapy for AIH.

PMID:42176246 | DOI:10.1007/s12602-026-11062-2

Biology (Basel). 2026 Mar 12;15(6):461. doi: 10.3390/biology15060461.

ABSTRACT

This study investigates the mechanisms underlying drought adaptability in Duolang sheep, a local breed from two distinct habitats in Xinjiang-an arid southern region and a grassland northern region-aiming to identify key factors driving differential environmental adaptation. Integrated multi-omics analyses were performed, including serum biochemical assays, untargeted metabolomics of perirenal and tail fat tissues, and transcriptomic profiling of lung, liver, and kidney samples. Our results revealed notable differences: (1) serum levels of GSH-Px, IL-2, and IgG were significantly higher in the southern group (p < 0.01); (2) metabolomic analysis identified key differential metabolites, including EPA (involved in unsaturated fatty acid biosynthesis), choline (glycerophospholipid metabolism), L-serine and glutathione (cofactor biosynthesis), and taurine (sulfur metabolism); and (3) transcriptomic analysis revealed significant differential expression of genes such as FGF21 (thermogenesis), CD14 and DUSP2 (MAPK signaling pathway), GOT1 (arginine biosynthesis), and AVPR2 (vasopressin-regulated water reabsorption). Integrative correlation analysis further indicated that glutathione, EPA, GOT1, and CD14 are involved in energy and lipid metabolism, while taurine, AVPR2, and DUSP2 contribute to oxidative stress resistance and immune regulation. These molecular and metabolic adjustments collectively enhance drought adaptability in southern Xinjiang Duolang sheep. In conclusion, adaptation to arid environments requires enhanced antioxidant capacity and immune function, with metabolites such as EPA supporting lipid metabolism and genes such as FGF21 regulating fatty acid oxidation to limit triglyceride accumulation.

PMID:41892221 | PMC:PMC13023672 | DOI:10.3390/biology15060461

Technol Cancer Res Treat. 2026 Jan-Dec;25:15330338261435022. doi: 10.1177/15330338261435022. Epub 2026 Mar 23.

ABSTRACT

IntroductionHepatocellular carcinoma (HCC) screening in patients with hepatic cirrhosis (HC) relies on ultrasound and alpha-fetoprotein (US + AFP), which has limitations in sensitivity, particularly for early-stage HCC detection. This study aims to evaluate the performance of a novel multi-omics blood test, HCCscreen, with its individual components (methylation, AFP, Des-γ-Carboxy Prothrombin (DCP), mutations) and the standard US + AFP for HCC screening in a hepatic cirrhotic population.MethodsA total of 5078 patients with known high-risk for HCC were recruited. A prospective screening study was conducted on 650 patients with hepatic cirrhosis identified by ultrasound. Blood samples were collected from all patients before the confirmation of diagnosis by imaging and/or pathological examinations. The performance of HCCscreen, individual markers and US + AFP were calculated and compared. Statistics was performed with Graphpad Prism 5.0.ResultsHCCscreen exhibited a sensitivity of 86.3% at a specificity of 81.3%, with a positive predictive value (PPV) of 28.2% and a negative predictive value (NPV) of 98.6%. The positive likelihood ratio (LR+) was 4.61 and the negative LR (LR-) was 0.17. The positive detection rate (PDR) for all markers increased with more advanced HCC stages, whether Barcelona Clinic Liver Cancer (BCLC) or clinical staging. Among the single-omics, methylation showed the highest PDR, followed by AFP, DCP and mutations. HCCscreen demonstrated superior overall performance with an AUC of 0.87, outperforming individual markers like methylation (AUC = 0.76), AFP (AUC = 0.83), and DCP (AUC = 0.77). Crucially, HCCscreen's PDR was significantly higher than US + AFP in early-stage HCC (BCLC-0 and clinical stage I). Furthermore, while AFP's PDR varied significantly by sex, HCCscreen's performance remained consistent across all demographics. Correlation analysis revealed a significant association only between the HCCscreen score and the methylation score.ConclusionsThe multi-omics approach of HCCscreen significantly enhances early HCC detection in patients with hepatic cirrhosis compared to both its individual components and the current standard of US + AFP. Its robust and consistent performance across patient demographics underscores its potential as a superior tool for population-wide early HCC screening.

PMID:41869803 | PMC:PMC13009828 | DOI:10.1177/15330338261435022

Technol Cancer Res Treat. 2026 Jan-Dec;25:15330338261435022. doi: 10.1177/15330338261435022. Epub 2026 Mar 23.

ABSTRACT

IntroductionHepatocellular carcinoma (HCC) screening in patients with hepatic cirrhosis (HC) relies on ultrasound and alpha-fetoprotein (US + AFP), which has limitations in sensitivity, particularly for early-stage HCC detection. This study aims to evaluate the performance of a novel multi-omics blood test, HCCscreen, with its individual components (methylation, AFP, Des-γ-Carboxy Prothrombin (DCP), mutations) and the standard US + AFP for HCC screening in a hepatic cirrhotic population.MethodsA total of 5078 patients with known high-risk for HCC were recruited. A prospective screening study was conducted on 650 patients with hepatic cirrhosis identified by ultrasound. Blood samples were collected from all patients before the confirmation of diagnosis by imaging and/or pathological examinations. The performance of HCCscreen, individual markers and US + AFP were calculated and compared. Statistics was performed with Graphpad Prism 5.0.ResultsHCCscreen exhibited a sensitivity of 86.3% at a specificity of 81.3%, with a positive predictive value (PPV) of 28.2% and a negative predictive value (NPV) of 98.6%. The positive likelihood ratio (LR+) was 4.61 and the negative LR (LR-) was 0.17. The positive detection rate (PDR) for all markers increased with more advanced HCC stages, whether Barcelona Clinic Liver Cancer (BCLC) or clinical staging. Among the single-omics, methylation showed the highest PDR, followed by AFP, DCP and mutations. HCCscreen demonstrated superior overall performance with an AUC of 0.87, outperforming individual markers like methylation (AUC = 0.76), AFP (AUC = 0.83), and DCP (AUC = 0.77). Crucially, HCCscreen's PDR was significantly higher than US + AFP in early-stage HCC (BCLC-0 and clinical stage I). Furthermore, while AFP's PDR varied significantly by sex, HCCscreen's performance remained consistent across all demographics. Correlation analysis revealed a significant association only between the HCCscreen score and the methylation score.ConclusionsThe multi-omics approach of HCCscreen significantly enhances early HCC detection in patients with hepatic cirrhosis compared to both its individual components and the current standard of US + AFP. Its robust and consistent performance across patient demographics underscores its potential as a superior tool for population-wide early HCC screening.

PMID:41869803 | PMC:PMC13009828 | DOI:10.1177/15330338261435022