Biology subjects

Ding, Y. C.

Publications and source records attributed to Ding, Y. C..

5 recordsLinked to original sources

bioRxiv2026

Spatial context of cellular heterogeneity in triple-negative breast cancer reveals actionable subtypes

Triple-negative breast cancer (TNBC) is an aggressive, heterogeneous disease with limited targeted treatment options. Leveraging bulk and spatial transcriptomics and cellular mapping of breast tissue from a large patient cohort, we identified three reproducible TNBC ecosystem subtypes that encode distinct spatial tumor-microenvironment architectures and clinically relevant treatment-response phenotype. Our analyses define: (1) an immune-exhausted subtype associated with immune checkpoint therapy (ICT); (2) a highly fibrotic/hypoxic subtype; and (3) a metabolically reprogrammed subtype characterized by nuclear-receptor and fatty-acid signaling. Spatial profiling further revealed subtype-specific organization of epithelial, immune, and stromal programs across tumor centers and invasive edges. Multiplexed imaging independently supported the contrasting immune-infiltrated and stromal-excluded architectures of the immune-engaged and fibrotic subtypes. The unique markers associated with the subtypes also provide the basis for subtyping and candidate therapeutic vulnerabilities. Our study provides a robust framework for personalized medicine, highlighting that targeting specific spatio-cellular architectures is critical to improving clinical outcomes.

cancer biology↗

bioRxiv2025

A novel subtyping method for TNBC with implications for prognosis and therapy

The biological heterogeneity of triple-negative breast cancer (TNBC) poses significant challenges for diagnosis, prognosis, and treatment. While prior TNBC subtype classifications exist, they are not widely used clinically. Here, we aimed to subtype TNBC based on transcriptomic profiles using cell type and state heterogeneity in tumor tissue from 250 pre-treatment women (127 African-American and 123 European-American). We identified three major subtypes and three distinct groups exhibiting unique cell-type composition and mechanisms: Subtype-1 immune signaling/T-cell response; Subtype-2 pro-fibrotic and immune desert; Subtype-3 fatty acid and nuclear receptor signaling. Subtype-1 showed potential responsiveness to immunotherapy, while Subtypes-2 and 3 suggested alternative therapeutic targets. In Subtype-3, which contained a patient group with high ESR1, (but not high ER protein expression) we identified putative mutations in the gene that are unique to these patients. This framework provides a path toward personalized TNBC treatment and is accessible through a user-friendly RShiny application for clinical use.

bioinformatics↗

bioRxiv2022

Profile of the somatic mutational landscape in breast tumors from Hispanic/Latina women

Breast cancer causes the most cancer deaths among Hispanic/Latinas (H/L). However, limited tumor-sequencing data from H/L are available to guide treatment. To address this gap, we performed whole-exome sequencing of DNA from 140 HL germline and 146 matched breast tumors and RNA-seq for the tumors. We generated somatic-mutation profiles, identified copy-number alterations (CNAs), and compared results to non-Hispanic White (White) women in The Cancer Genome Atlas. Similar to Whites, PIK3CA and TP53 were the most commonly mutated genes in breast tumors from H/L. We found 4 common COSMIC mutation signatures (1, 2, 3, 13) and signature 16 not previously reported in other breast-cancer datasets. We observed recurrent amplifications in breast-cancer drivers including MYC, FGFR1, CCND1, and ERBB2, and a recurrent amplification on 17q11.2 associated with high KIAA0100 gene expression, implicated in breast-cancer aggressiveness. Expanded research is required to determine how these characteristics of H/L tumors impact treatment response and survival.

cancer biology↗

bioRxiv2022

Variable Number Tandem Repeats (VNTRs) as modifiers of breast cancer risk in carriers of BRCA1 185delAG

Despite substantial efforts in identifying both rare and common variants affecting disease risk, in the majority of diseases, a large proportion of unexplained genetic risk remains. We propose that variable number tandem repeats (VNTRs) may explain a proportion of the missing genetic risk. Herein, we tested whether VNTRs are causal modifiers of breast cancer risk in 347 female carriers of BRCA1 185delAG, an important group given their high risk of developing breast cancer. We performed targeted-capture to sequence VNTRs, called genotypes with adVNTR, and tested the association of VNTRs and breast cancer risk using Cox regression models. Of 303 VNTRs that passed quality control checks, 4 VNTRs were significantly associated with risk to develop breast cancer at false discovery rate [FDR] < 0.05 and an additional 4 VNTRs had FDR < 0.25. After determining the specific risk alleles, there was a significantly earlier age at development of breast cancer in carriers of the risk genotypes compared to those without the risk genotypes for seven of eight VNTRs. Results from this first systematic study of VNTRs demonstrate that VNTRs may explain a proportion of the unexplained genetic risk for disease and have larger effects than SNPs.

cancer biology↗

bioRxiv2018

Identification of Novel Common Breast Cancer Risk Variants in Latinas at the 6q25 Locus

Background: Breast cancer is a partially heritable trait and over 180 common genetic variants have been associated with breast cancer in genome wide association studies (GWAS). We have previously performed breast cancer GWAS in Latinas and identified a strongly protective single nucleotide polymorphism (SNP) at 6q25 with the protective minor allele originating from Indigenous American ancestry. Here we report on additional GWAS and replication in Latinas.\n\nMethods: We performed GWAS in 2385 cases and 7342 controls who were either U.S. Latinas or Mexican women. We replicated 2412 cases and 1620 controls of U.S Latina, Mexican, and Colombian women. In addition, we replicated the top novel variants in study of African American and African women and in one study of Chinese women. In each dataset we used logistic regression models to test the association between SNPs and breast cancer risk and corrected for genetic ancestry using either principal components or genetic ancestry inferred from ancestry informative markers using a model based approach.\n\nResults: We identified 3 SNPs (p=1.9x10-8 - 2.8x10-8) at 6q25 locus not in linkage disequilibrium (LD) with variants previously reported at this locus. These SNPs were in high LD with each other, with the top SNP, rs3778609, associated with breast cancer with an odds ratio (OR) and 95% confidence interval (95% CI) of 0.75 (0.68-0.83). In a replication in women of Latin American origin, we also observed a consistent effect (OR: 0.88; 95% CI: 0.78-0.99; p=0.037). Since the minor allele was common in East Asians and African American but not European ancestry populations, we replicated in a meta-analysis of those populations and also observed a consistent effect (OR 0.94; 95% CI: 0.91 - 0.97; p=0.013).\n\nConclusion: The effect size of this variant is relatively large compared to other common variants associated with breast cancer and adds to evidence about the importance of the 6q25 locus for breast cancer susceptibility. Our finding also highlights the utility of performing additional searches for genetic variants for breast cancer in non-European populations.

genetics↗