Biomedical subjects

Jie Mao

Publications and source records attributed to Jie Mao.

3 recordsLinked to original sources

PubMed2026

Secreted protein circuits in the gastrointestinal tumour microenvironment: determinants of immunotherapy response and resistance.

Immune checkpoint blockade has transformed treatment in selected gastrointestinal (GI) cancers, yet primary resistance, incomplete responses and acquired resistance remain common. This heterogeneity is not explained by tumour-cell genomics alone; extracellular signalling programmes within the tumour microenvironment can determine immune recruitment, access and adaptation to therapy. The tumour secretome-including cytokines, chemokines, growth factors, complement components, matricellular proteins, soluble checkpoint molecules and extracellular-vesicle-associated cargo-regulates immune-cell recruitment, exclusion, suppression, tertiary lymphoid structure formation and exhaustion across anatomical and molecular contexts. Across gastric and esophageal cancers, colorectal cancer, pancreatic ductal adenocarcinoma, hepatocellular carcinoma and biliary tract cancers, recurrent suppressive circuits include TGF-β, VEGF, CXCL12-CXCR4, CXCL8/IL-8-CXCR1/2, CCL2-CCR2, CSF1-CSF1R, IL-6-family cytokines, SPP1/osteopontin, periostin, galectins, DKK1, MIF, complement and soluble or vesicular PD-L1. Conversely, CXCL9/10/11-CXCR3 signalling and CXCL13-associated tertiary lymphoid structures characterise immune-permissive states that can support checkpoint responsiveness. We organise these circuits into four overlapping functional modules-myeloid-enriched, fibroblast-driven exclusion, angiogenic-immunosuppressive and immune-permissive-and apply a four-level evidence hierarchy that separates clinical validation from mechanistic inference. Clinically useful secretome biomarkers will therefore need to integrate cellular source, spatial localisation, receptor context, temporal dynamics and linkage to actionable immune-state transitions.

Humans↗

PubMed2026

Comprehensive Multiplatform Tyrosine Kinase Profiling Reveals Novel Actionable FGFR Aberrations across Sarcomas Affecting the Young.

Limited targeted agents are approved for pediatric sarcomas. Tyrosine kinase (TK) inhibitors (TKi) have shown clinical efficacy in some, but not all, young patients with sarcoma. A major obstacle preventing further advances and clinical implementation is the lack of predictive response biomarkers to guide TK-targeted treatments. TK-activating fusions or mutations are rare in these patients. RNA overexpression of TKs is a frequent feature. The unresolved question is when upregulated TK expression is associated with kinase activation and signaling dependence. We explored the TK molecular landscape of 107 patients with sarcoma from the ZERO Childhood Cancer Precision Medicine Program (ZERO) using whole-genome and -transcriptome sequencing. Phosphoproteomic analyses of tyrosine phosphorylation (pY) and functional in vitro and in vivo assays were performed in cell lines and patient-derived xenografts (PDX). Our analysis shows that although novel genomic driver lesions are rare, when present they are therapeutically actionable as exemplified by a novel LSM1-FGFR1 fusion identified in a patient with osteosarcoma. We further show that in certain contexts, TK RNA expression can indicate TK pathway activity and predict TKi sensitivity. We highlight the utility of FGFR inhibitors in PAX3-FOXO1 fusion-positive rhabdomyosarcomas (FP-RMS) characterized by high FGFR4 and FGF8 RNA expression levels and FGFR4 activation (FGFR4_pY). We demonstrate marked tumor growth inhibition in all FP-RMS PDXs treated with single-agent FGF401 (FGFR4-specific inhibitor) and single-agent lenvatinib (multikinase FGFR inhibitor) and report a clinical response to lenvatinib in a patient with relapsed metastatic FP-RMS. Altogether, we identified new patients with sarcoma who may benefit from FGFR inhibitors, most notably FP-RMS via FGFR4/FGF8 coexpression.

Journal Article↗

PubMed2024

Protein-losing enteropathy with congenital kidney stones in a 2-month-old boy: a rare case report and literature review.

BACKGROUND: Protein-losing enteropathy (PLE) is a rare condition featured by severe loss of proteins through the gastrointestinal tract. Rare PLE cases complicated with congenital kidney stones have been reported. This case study aimed to illustrate our experiences on the diagnosis and treatment of PLE and congenital kidney stones in a neonate. CASE PRESENTATION: A 10-day-old boy fed on breast milk presented to our department because of severe diarrhea, which showed no significant attenuation after free amino acid milk formula. Gastrointestinal endoscopy revealed absence of brush border of surface villi. Genetic testing was strongly recommended given intractable early-onset diarrhea, severe malnutrition and hypoalbuminemia. Then the patient was diagnosed with PLE based on the clinical manifestations and identification of DGAT1 gene by whole-exome sequencing. The patient underwent percutaneous suprapubic cystostomy to remove the urine, and ultrasonography examination showed kidney stones. CONCLUSIONS: We reported a rare newborn with PLE and congenital kidney stones carrying DGAT1 mutations.

Humans↗