Proteomic insights into lymph node metastasis in breast cancer subtypes: Key biomarkers and pathways

Abstract

Background: Breast cancer (BC) is a significant global cause of death in women, primarily due to its diversity and metastatic potential.

Methods: BC, healthy lymph node (HL), and metastatic lymph node (ML) tissues were collected from 19 patients diagnosed with infiltrating ductal carcinoma. Protein isolation was performed, followed by two-dimensional gel electrophoresis (2DE) and mass spectrometry (MALDI-TOF/TOF) to identify differentially expressed proteins. Bioinformatic analyses, including protein-protein interaction networks and molecular pathways, were conducted using STRING. Kaplan-Meier analysis was performed with KM plotter to evaluate the prognostic significance of identified proteins. Receiver operating characteristic (ROC) curves were generated using TCGA and GTEx data from UCSC Xena and easyROC to assess diagnostic relevance.

Results: Distinct pathways related to cytoskeletal regulation, immune modulation, and oxidative stress response were enriched in each subtype. Key proteins such as TUBA1C, CCT6A, and Vimentin (LNA), CAPZB and ENO1 (LNB), GSTO1 (HER2 OE), and CORO1A and LAP3 (TNBC) were identified as significant in driving metastatic behavior. KM survival analysis showed that CAPZB (LNB) and CORO1A (TNBC) were associated with patient outcomes, while GSTO1 was linked to improved distant metastasis-free survival in HER2 OE. ROC analysis highlighted CAPZB as a strong diagnostic marker.

Conclusions: These findings form a basis for comprehending the molecular mechanisms underlying metastasis in different subtypes of breast cancer. They may lead to the identification of new therapeutic targets for customized interventions against invasion and metastasis. Further validation is required to confirm their clinical utility in larger cohorts.

Keywords: Biomarker; Breast Cancer; Breast Cancer Subtypes; Lymph Node Metastasis; Proteome.