Molecular Biomarkers Screened by Next-Generation RNA Sequencing for Non-Sentinel Lymph Node Status Prediction in Breast Cancer Patients with Metastatic Sentinel Lymph Nodes

Background: Non-sentinel lymph node (NSLN) status prediction with molecular biomarkers may make some sentinel lymph node (SLN) positive breast cancer patients avoid the axillary lymph node dissection, but the available markers remain limited.Methods: SLN positive patients with and without NSLN invasion were selected, and genes differentially expressed or fused in SLN metastasis were screened by next-generation RNA sequencing.Results: Six candidates (all ER/PR+, HER2-, Ki-67 <20 %) with metastatic SLNs selected from 305 patients were equally categorized as NSLN negative and positive. We identified 103 specifically expressed genes in the NSLN negative group and 47 in the NSLN positive group. Among them, FABP1 (negative group) and CYP2A13 (positive group) were the only 2 protein-encoding genes with expression levels in the 8th to 10th deciles. Using a false discovery rate threshold of <0.05, 62 up-regulated genes and 98 down-regulated genes were discovered in the NSLN positive group. Furthermore, 10 gene fusions were identified in this group with the most frequently fused gene being IGLL5.Conclusions: The biomarkers screened in present study may broaden our understanding of the mechanisms of breast cancer metastasis to the lymph nodes and contribute to the axillary surgery selection for SLN positive patients.