Transl Cancer Res. 2026 Apr 30;15(4):314. doi: 10.21037/tcr-2025-aw-2503. Epub 2026 Mar 20.

ABSTRACT

BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most common lung cancer subtypes worldwide, and its aggressive subtype invasive adenocarcinoma (IAC) has low survival rates. The precise identification of IAC is vital for the clinical diagnosis and treatment. The purpose of this study is to identify novel biomarkers for LUAD using single-cell and bulk RNA sequencing, so as to provide theoretical basis and practical support for the diagnosis, treatment and prognosis evaluation of lung invasive adenocarcinoma.

METHODS: We employed a combination of transcriptomic analysis and single-cell analysis to investigate the molecular characteristics and immune microenvironment of four subtypes of LUAD, including atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and IAC, with the aim of screening for biomarkers to differentiate pre-invasive lesions from invasive lesions.

RESULTS: Transcriptomic and single-cell analyses revealed that IAC subtypes demonstrated the most substantial molecular differences, particularly in immune cell infiltration and immune-related gene expression. Three genes-CD27, TIGIT, and TNFRSF18-that were significantly upregulated in IAC, predominantly expressed in immune cells and closely linked to immune regulatory pathways. We further analyzed T cell subpopulations in the IAC subtype and explored the expression of transcription factors (TFs) corresponding to these three genes, revealing their critical roles in immune cell function. Additionally, communication between T cells and other cells showed significantly enhanced signaling pathways, particularly those related to immune co-stimulatory molecules and inflammation pathways. Immunohistochemical validation of clinical samples showed that these three genes have high diagnostic value in IAC subtypes. These findings establish a crucial biological foundation for diagnosis, classification, and immunotherapy of LUAD, which contributes to the development of individualized treatment strategies.

CONCLUSIONS: This study identifies a three-gene signature (CD27, TIGIT, and TNFRSF18) that not only distinguishes invasive from pre-invasive LUAD with high precision by capturing the immune checkpoint disequilibrium characteristic of IAC, but also provides a clinically actionable biomarker panel for preoperative diagnosis and personalized immunotherapy strategies.

PMID:42180871 | PMC:PMC13190665 | DOI:10.21037/tcr-2025-aw-2503

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

Nat Commun. 2026 Mar 12. doi: 10.1038/s41467-026-70376-5. Online ahead of print.

ABSTRACT

Myasthenia gravis (MG) is an autoimmune disorder characterized by impaired neuromuscular transmission and motor symptoms. Its genetic background remains unclear, particularly beyond specific subtypes reported in European populations. Here, we perform a genome-wide association study (GWAS) of 1,434 MG cases covering all disease subtypes and 42,913 controls of Japanese, which newly identify the TERT locus (odds ratio [OR] = 1.31, P = 1.7×10^-10). Subtype-stratified GWASs show stronger signals for generalized MG (gMG; OR = 1.38, P = 1.6×10^-12), anti AChR antibody-positive gMG (g-AChR-Ab(+)MG; OR= 1.49, P = 2.1×10^-15), and thymoma-associated gMG (g-TAMG; OR = 1.92, P = 1.1×10^-15). Fine-mapping of the major histocompatibility complex region reveal distinct associations of HLA-DRB1 with late onset gMG (g-LOMG) and HLA-A with early onset gMG (g-EOMG). The MG risk TERT lead variant rs2736099 is associated with poor treatment response, especially in g-AChR-Ab(+)MG and g-EOMG (P < 0.0042). The biobank-based phenome-wide association study identify pleiotropic effects on lung cancer, hematological traits, and telomere length. Single cell transcriptomics and immunohistochemistry identified immature lymphocyte-specific TERT expression in thymoma specimens. Full-length transcriptomics reveal allele-specific decreasing effect of rs2736099-A on TERT expression. Our study unveils genetics of MG distinctly across disease subtypes, and involvement of TERT in its pathogenesis.

PMID:41820352 | DOI:10.1038/s41467-026-70376-5