Integrating Proteomics and Bioinformatics Methods for the Identification of Breast Cancer Biomarkers Interacting with Telomeric G-Quadruplex

ABSTRACT: The identification of reliable biomarkers is imperative for enhancing early detection, prognosis, and treatment of breast cancer. This study investigates a human telomeric dimeric G-quadruplex (G4) model, Tel46, which has been functionalized on Controlled Pore Glass (CPG) support, as a novel tool for biomarker discovery. Tel46 closely mimics multimeric G4 structures found in telomeric overhangs. Utilizing the affinity purification-mass spectrometry (AP-MS) approach, we identified 93 nuclear proteins that interacted with Tel46 in MCF7 breast cancer cells. Functional enrichment analyses revealed that these proteins were linked to DNA replication, repair, and genome stability pathways, which are frequently altered in cancer. To further refine these findings, we integrated AP-MS data with quantitative proteomics, comparing MCF7 and non-tumorigenic MCF10a cells. This approach led to the identification of 27 Tel46 interactors that were overexpressed. The subsequent functional analyses of these proteins revealed their enrichment in DNA replication, damage repair, and genome maintenance pathways, emphasising their potential as cancer biomarkers. Conversely, the downregulated proteins were associated with basic cellular functions such as protein synthesis and cytoskeletal organisation. Subsequent bioinformatics analyses incorporating public cancer genomics and transcriptomics data identified 19 potential biomarkers, including MSH6, MSH2, ESRP1, and WDHD1, which were further linked to poor clinical outcomes in breast cancer subtypes. This study validates the use of Tel46-functionalized CPG as a novel tool for isolating cancer-related proteins and highlights the potential of telomeric G4-interacting proteins as biomarkers for breast cancer diagnosis and therapy. These findings provide a foundation for future research into G4-mediated molecular mechanisms in cancer.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Flora Cozzolino  

LAB HEAD: maria monti

PROVIDER: PXD059597 | Pride | 2025-09-15

REPOSITORIES: Pride