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Zhi-Ming Shao

Publications and source records attributed to Zhi-Ming Shao.

4 recordsLinked to original sources
PubMed2026

Integrated analysis reveals the impact of obesity on triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly aggressive and heterogeneous breast cancer subtype with limited therapeutic options. While the prevalence of overweight/obese (OW/OB) women continues to rise, the impact of obesity on molecular features of TNBC remains incompletely understood. We investigated clinicopathological and molecular data (including genomic, transcriptomic, proteomic and metabolomic profiling) using our original multi-omics database of TNBC (N = 465) for associations with patient body mass index (BMI). Multi-omics profiling revealed that OW/OB patients exhibited worse survival as well as elevated inflammation of tumor microenvironment, higher expression of immune checkpoints, and dysregulated lipid metabolism. Our in vivo experiments demonstrated that tumors in obese mice displayed faster growth rates, a higher proportion of PD-1+CD8+ T cells and enhanced responsiveness to anti-PD-1 treatment. In addition, we analyzed data from four independent clinical trials and discovered that OW/OB patients demonstrated higher pathological complete response rates and longer progression-free survival following anti-PD-1-based immunotherapy. In conclusion, our study systematically revealed that obesity is associated with coordinated immune-metabolic remodeling in TNBC, characterized by checkpoint enrichment and lipid dysregulation, which may help explain the enhanced anti-PD-1 responsiveness and should be taken into account in the field of precision medicine.

Immunity↗
PubMed2026

Spatial proteogenomic profiling uncovers sensitization strategies for antibody-drug conjugate in HER2-positive breast cancer.

Antibody-drug conjugates (ADCs) have transformed the treatment of HER2-positive breast cancer, yet resistance remains poorly understood. Using imaging mass cytometry, we profiled 157 regions of interest comprising 912,360 single cells from 47 HER2-positive/hormone receptor-negative breast cancers treated with SHR-A1811 in the FASCINATE-N trial. Spatial proteomic analyses identified two determinants of ADC response: elevated tumor-cell H3K27ac expression was associated with improved ADC efficacy, whereas collagen-positive fibroblasts mediated resistance. Combining ADC with the histone deacetylase inhibitor chidamide or the collagen-modulating agent losartan produced synergistic antitumor effects in preclinical models. These biomarkers and therapeutic vulnerabilities were independently validated in patients with advanced HER2-positive disease receiving trastuzumab deruxtecan. Moreover, based on these spatial features, we developed a clinically applicable ADC barrier prediction model that can be implemented using multiplex immunofluorescence. Taken together, our findings reveal actionable spatial determinants of ADC efficacy and suggest potential combination therapeutic strategies.

Humans↗
PubMed2026

Age-related genomic characterization and therapeutic targets in Chinese breast cancer: insights from prospective targeted sequencing and clinical data analysis.

BACKGROUND: In China, breast cancer occurs at a much younger age and has a higher recurrence and mortality rate. However, with changes in lifestyle, there has been a trend towards an older age of breast cancer incidence in Chinese women. There is a paucity of large-scale next-generation sequencing cohorts for the analysis of genomic characterization in these populations and the identification of potential therapeutic targets. METHODS: To address this gap, we performed prospective targeted sequencing of tumor and blood samples from Chinese patients and collected detailed clinical information. We then categorized patients into two groups based on age (<&#x2009;40&#xa0;years, n&#x2009;=&#x2009;637;&#x2009;&#x2265;&#x2009;40&#xa0;years, n&#x2009;=&#x2009;3442) and proceeded to provide comprehensive descriptions of somatic and germline mutations in both groups. RESULTS: The somatic mutation analysis revealed that PIK3CA, FOXA1, and TBX3 mutations were more prevalent in elderly patients. By leveraging the aforementioned mutational characteristics, we employed our institution's FUTURE-SUPER clinical trial, an umbrella study targeting metastatic breast cancer, to confirm the potential benefits of PI3K-AKT-mTOR pathway inhibitors among elderly patients with breast cancer. Furthermore, TP53 and ERBB2 were more likely to be co-mutated in young women. Patients with TP53 and ERBB2 co-mutation tend to have a poorer prognosis, but through investigation of the SPARK cohort, patients carrying the TP53 and ERBB2 co-mutation are more likely to benefit from immune checkpoint inhibitor combination with tyrosine kinase inhibitor therapy. In our study, we observed a higher frequency of mutations in the DNA homology-dependent recombination pathway in young patients with breast cancer, which was associated with an elevated Ki67 index. Additionally, we confirmed a significant prevalence of germline breast cancer susceptibility gene 1 (gBRCA1) mutations in young patients, whereas germline checkpoint kinase 2 (gCHEK2) mutations are more common in elderly patients. CONCLUSIONS: Our study, which makes use of the largest Chinese breast cancer sequencing cohort, sought to characterize the age-related genomic profile of breast cancer patients and identify novel therapeutic opportunities for individuals with breast cancer.

Adult↗