Transl Oncol. 2026 Sep 9;73:103020. doi: 10.1016/j.tranon.2026.103020. Online ahead of print.

ABSTRACT

BACKGROUND: The prognostic relevance of inflammatory bowel disease (IBD)-colorectal cancer (CRC) shared host-microbe signatures in non-intestinal epithelial malignancies remains unclear. This study aimed to evaluate the prognostic and biological significance of an IBD-CRC shared host-microbe interactome signature in bladder urothelial carcinoma (BLCA).

METHODS: Gene set variation analysis (GSVA) was used to assess the activity of the IBD-CRC shared signature across The Cancer Genome Atlas (TCGA) pan-cancer solid tumor cohorts, including lung, liver, colorectal, and urinary system tumors. In BLCA, weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO)-Cox regression were applied to construct a prognostic risk model, which was validated in independent transcriptomic cohorts. An attention-based multiple instance learning (MIL) model was developed to predict the LASSO-derived high- or low-risk group from H&E whole-slide images (WSIs), using TCGA cases for training and internal validation and an independent institutional cohort of 39 BLCA patients for external validation. Molecular subtype, immune infiltration, immunohistochemistry (IHC), machine learning, single nucleotide variation/copy number variation (SNV/CNV), single-cell/spatial transcriptomics, and WSI-based deep learning analyses were integrated to characterize the biological relevance of the signature.

RESULTS: High GSVA scores were significantly associated with poor prognosis in BLCA. The LASSO-derived high-risk group was enriched in basal/squamous molecular features and exhibited an immune-infiltrated but immunosuppressive tumor microenvironment, characterized by increased immunosuppressive cell infiltration and elevated immune checkpoint expression. Conventional IHC markers supported distinct subtype-related protein phenotypes between risk groups. Single-cell and spatial transcriptomic analyses revealed that malignant cells with high signature activity were enriched in Wnt, Hippo, and cell adhesion pathways. The WSI-based MIL model achieved an area under the curve (AUC) of 0.852 in the internal validation cohort. Machine learning and SNV/CNV analyses further characterized key molecular features associated with the LASSO risk score, including AKR1B1, LY6E, MEST, and others. Pan-cancer characterization of AKR1B1 across multiple malignancies, including lung adenocarcinoma (LUAD), liver hepatocellular carcinoma (LIHC), and kidney renal clear cell carcinoma (KIRC), revealed cancer-type-specific associations with immunosuppressive microenvironmental features and tumor stemness.

CONCLUSION: The IBD-CRC shared host-microbe signature has significant prognostic value in BLCA and is associated with basal/squamous differentiation, immunosuppressive microenvironmental features, genomic alteration patterns, and malignant cell functional heterogeneity. The integrated multi-omics framework and externally validated pathology AI model provide potential tools for BLCA risk stratification and biological interpretation.

PMID:42715652 | DOI:10.1016/j.tranon.2026.103020

Transl Oncol. 2026 Sep 8;73:102990. doi: 10.1016/j.tranon.2026.102990. Online ahead of print.

ABSTRACT

BACKGROUND: Lung adenocarcinoma (LUAD) is a predominant and lethal subtype of non-small cell lung cancer, with a lack of reliable prognostic biomarkers to guide clinical management. Basigin (BSG) has been implicated in tumor progression across multiple cancers, yet its expression pattern, prognostic significance, and underlying mechanisms in LUAD remain incompletely elucidated.

METHODS: We integrated multi-omics data from TCGA, GTEx, CCLE, and GEO databases to analyze BSG expression profiles. Clinical correlations were assessed via Kruskal-Wallis tests. Prognostic value was determined using Kaplan-Meier survival analysis, univariate/multivariate Cox regression, and nomogram construction with calibration curves. Functional enrichment (GO/KEGG) and immune infiltration analyses were performed to explore BSG-related mechanisms, followed by immunohistochemical (IHC) validation in A549 cells and clinical LUAD tissue microarrays.

RESULTS: BSG was significantly upregulated in LUAD tissues versus normal/paired adjacent tissues, correlating with advanced T/N/pathologic stages. High BSG expression predicted worse survival outcomes in TCGA-LUAD, which was validated in GEO datasets. Multivariate Cox regression identified BSG as an independent prognostic factor, with a well-calibrated nomogram for survival prediction. Functional exploration indicated that BSG mainly participated in tumor-associated and immunological pathways. Immune infiltration analysis indicated that BSG was significantly correlated with the infiltration of various immune cells. Moreover, BSG exhibited a strong association with immune checkpoint proteins, chemokines, chemokine receptors, and MHC genes. IHC further confirmed its cytoplasmic/membranous localization and prognostic relevance.

CONCLUSION: BSG serves as an independent prognostic biomarker and potential therapeutic target in LUAD, shedding light on its regulatory roles in tumor progression and immune microenvironment remodeling.

PMID:42710246 | DOI:10.1016/j.tranon.2026.102990

J Vis Exp. 2026 Mar 13;(229). doi: 10.3791/70383.

ABSTRACT

This study utilized a multi-omics and computational biology framework to investigate the therapeutic potential of the Traditional Chinese Medicine (TCM) formula Buti Huatan Tang (BTHTT) against chronic obstructive pulmonary disease (COPD). Significant physiological improvements were observed in a rat model following BTHTT intervention. Histological analysis showed a reversal of lung pathological damage, while biochemical assays, and transcriptomics confirmed the normalization of IL-1β and IL-1R2 levels. Additionally, metabolic profiling revealed that BTHTT corrected disruptions in T3 and T4 thyroid hormone levels. A negative correlation was observed between the IL-1β/IL-1R2 axis and these thyroid hormones, indicating that their regulation is associated with the formula's therapeutic effect. Beyond direct measurements, machine learning algorithms identified ten COPD signature genes from clinical databases. Pathway enrichment analysis suggests that BTHTT may act through cytokine-cytokine-receptor interactions and thyroid hormone synthesis pathways. Furthermore, while 283 components were identified in vivo, compounds such as tanshinone IIA and cryptotanshinone are currently considered candidate active substances. Their role as primary drivers is supported by a model in which they stably bind to IL-1R2; this inference is based on molecular docking and molecular dynamics (MD) simulations rather than direct experimental isolation. Overall, the data support a model in which BTHTT exerts a multi-target effect on COPD by modulating inflammation and metabolic homeostasis. This integrated approach provides a refined scientific basis for the clinical application of BTHTT and highlights specific pathways for future experimental validation.

PMID:41911070 | DOI:10.3791/70383

Nat Commun. 2026 Mar 20;17(1):2655. doi: 10.1038/s41467-026-70193-w.

ABSTRACT

Pulmonary fibrosis represents a progressive interstitial lung disease marked by excessive extracellular matrix deposition and architectural distortion. Vascular endothelial cells critically contribute to fibrogenesis through paracrine secretion of pro-fibrotic mediators, yet their mechanobiological regulation remains elusive. Using integrated single-cell multi-omics profiling of human pulmonary fibrosis specimens and experimental fibrosis models induced by bleomycin or silica, we identify mechanosensitive Piezo1 upregulation in Endothelial cells as a hallmark of fibrotic progression. Endothelial-specific Piezo1 knockout significantly attenuates Bleomycin-induced fibrotic remodeling in male mice, establishing its pathogenic necessity. Mechanistically, PIEZO1 activation promotes pulmonary fibrosis development via CAPN2-mediated STAT3 phosphorylation, which may regulate the secretion of the pro-fibrotic molecule interleukin-33. These findings suggest that the endothelial PIEZO1-CAPN2-STAT3-IL33 axis is a potential therapeutic target for PF intervention.

PMID:41862476 | PMC:PMC13004862 | DOI:10.1038/s41467-026-70193-w