Proteomic profiling reveals biological processes and biomarkers involved in the pathogenesis of occult breast cancer

Abstract

Background

Occult breast cancer (OBC) is defined as axillary lymph node metastasis without any evidence of a primary tumor in the breast. Because of the limited number of clinical cases, the clinicopathological features and treatment recommendations of OBC are still controversial. In addition, its natural history is poorly understood and its proteomic signature remains unknown.

Materials and Methods

We compared the clinicopathological features and prognosis of OBC patients and Non-OBC patients from the Surveillance, Epidemiology, and End Results (SEER) database and analyzed the effects of local treatment on the survival outcomes of OBC patients. Additionally, we performed a quantitative proteomic analysis for tissue samples of metastatic lymph nodes from OBC patients (OBC-LN), and paired tissue samples of metastatic lymph nodes (Non-OBC-LN) and primary tumors (Non-OBC-PT) from Non-OBC patients. We identified differentially expressed proteins in different comparable groups using Student’s t test. Functional enrichment and protein–protein interaction network analyses were used to interpret the functions and interactions of the differentially expressed proteins in the comparison of OBC-LN vs Non-OBC-LN. Immunohistochemistry was used for the validation of the hub proteins.

Results

Analysis of data from the SEER database demonstrated that OBC patients had a better prognosis than Non-OBC patients did and that either mastectomy or radiation therapy improved the outcomes of OBC patients. A total of 7208 comparable proteins were successfully quantified. Compared with those of the Non-OBC-LN samples, the OBC-LN protein profiles exhibited an active extracellular matrix and a thoroughly upregulated epithelial-mesenchymal transition phenotype. COL1A1, COL1A2, COL3A1, MMP2 and LUM were overexpressed in the OBC-LN samples and were identified as hub proteins. Immunohistochemical staining demonstrated that the five hub proteins were overexpressed in OBC-LN samples.

Conclusion

Our results provide insights for the clinical management of OBC and the proteomic signature of OBC offers molecular basis for further biological research.