Nanoproteomics deciphers the prognostic value of EGFR family proteins-based liquid biopsy.

Monitoring tumor-associated protein status in serum can effectively track tumors and avoid time-consuming, costly, and invasive tissue biopsy. Epidermal growth factor receptor (EGFR) family proteins are often recommended in the clinical management of multiple solid tumors. However, the low-abundance of serum EGFR (sEGFR) family proteins hinders the depth-understanding of their function and tumor management. Herein, a nanoproteomics approach coupling with aptamer-modified MOFs (NMOFs-Apt) with mass spectrometry was developed for the enrichment and quantitative analysis of sEGFR family proteins. This nanoproteomics approach exhibited high sensitivity and specificity for sEGFR family protein quantification, with the limit of quantification as low as 1.00 nM. After detecting 626 patients' sEGFR family proteins with various malignant tumors, we concluded that the levels of serum proteins had a moderate concordance with tissue counterparts. Metastatic breast cancer patients with a high level of serum human epidermal growth factor receptor 2 (sHER2) and a low level of sEGFR had a poor prognosis, and patients with a sHER2 decrease of more than 20% had longer disease-free time after receiving chemotherapy. This nanoproteomics method provided a simple and effective approach for low-abundant serum protein detection and our results clarified the potential of sHER2 and sEGFR as cancer markers.