Serum Proteome Profiling Identifies N-Cadherin and C-Met as Early Marker Candidates of Therapeutic Response to Neoadjuvant Chemotherapy in Breast Cancer

Breast cancer remains the most common cancer in women worldwide. Neoadjuvant chemotherapy (NACT) is often preferred to adjuvant chemotherapy to achieve tumour shrinkage, monitor response to therapy and facilitate surgical removal in the absence of metastases. In addition, there is strong evidence that pathological complete remission (pCR) is associated with prolonged survival. In this study, we sought to identify candidate markers that signal response or resistance to therapy. We present a retrospective longitudinal serum proteomic study of 22 breast cancer patients (11 with pCR and 11 with non-pCR) matched with 21 healthy controls. Serum was analysed by LC-MS/MS after depletion of abundant proteins by immunoaffinity, trypsinisation, isobaric labelling and fractionation by reversed-phase HPLC. We observed an inverse behaviour of the serum proteins c-Met and N-cadherin after the second cycle of chemotherapy with a high predictive value (AUC 0.93). More pronounced changes were observed after the 6th cycle of NACT, with significant changes in the intensity of the proteins contactin-1, centrosomal protein, sex hormone-binding globuline and cholinesterase. Our study highlights the possibility of monitoring response to NACT using serum as a liquid biopsy.