Plasma Proteome Signature to Predict the Outcome of Breast Cancer Patients Receiving Neoadjuvant Chemotherapy

SIMPLE SUMMARY: The prognostic impact of plasma protein biomarkers in breast cancer patients treated with neoadjuvant chemotherapy (NCT) was evaluated using a proteomics approach. Three biomarkers were identified among differentially expressed proteins. The plasma concentration of APOC3 was higher in the pathological complete response (pCR) group, whereas MBL2, ENG, and P4HB were upregulated in the non-pCR group. Univariate survival analysis was performed to identify protein biomarkers that could classify patients into low- and high-risk groups. The results showed that MBL2 and P4HB were statistically significantly associated with disease-free survival (log-rank test p < 0.05); P4HB was statistically significantly associated with overall survival (log-rank test p < 0.05), whereas MBL2 was statistically significantly associated with distant metastasis-free survival (log-rank test p < 0.05). The results demonstrated that protein markers from non-invasive liquid biopsy sampling correlate with pCR and survival in breast cancer patients receiving NCT. Further investigation of these protein markers may help clarify their role in predicting prognosis and thus their therapeutic potential for preventing metastasis. ABSTRACT: The plasma proteome of 51 non-metastatic breast cancer patients receiving neoadjuvant chemotherapy (NCT) was prospectively analyzed by high-resolution mass spectrometry coupled with nano-flow liquid chromatography using blood drawn at the time of diagnosis. Plasma proteins were identified as potential biomarkers, and their correlation with clinicopathological variables and survival outcomes was analyzed. Of 51 patients, 20 (39.2%) were HR+/HER2-, five (9.8%) were HR+/HER2+, five (9.8%) were HER2+, and 21 (41.2%) were triple-negative subtype. During a median follow-up of 52.0 months, there were 15 relapses (29.4%) and eight deaths (15.7%). Four potential biomarkers were identified among differentially expressed proteins: APOC3 had higher plasma concentrations in the pathological complete response (pCR) group, whereas MBL2, ENG, and P4HB were higher in the non-pCR group. Proteins statistically significantly associated with survival and capable of differentiating low- and high-risk groups were MBL2 and P4HB for disease-free survival, P4HB for overall survival, and MBL2 for distant metastasis-free survival (DMFS). In the multivariate analysis, only MBL2 was a consistent risk factor for DMFS (HR: 9.65, 95% CI 2.10–44.31). The results demonstrate that the proteomes from non-invasive sampling correlate with pCR and survival in breast cancer patients receiving NCT. Further investigation may clarify the role of these proteins in predicting prognosis and thus their therapeutic potential for the prevention of recurrence.