Plasma proteome profiling reveals biomarkers of chemotherapy resistance in patients with advanced colorectal cancer

Abstract

Colorectal cancer (CRC) is one of the most common cancers. Patients with advanced CRC can only rely on chemotherapy to improve outcomes. However, primary drug resistance frequently occurs and is difficult to predict. Changes in plasma protein composition have shown potential in clinical diagnosis. Thus, it is urgent to identify potential protein biomarkers for primary resistance to chemotherapy for patients with CRC. Automatic sample preparation and high‐throughput analysis were used to explore potential plasma protein biomarkers. Drug susceptibility testing of circulating tumor cells (CTCs) has been investigated, and the relationship between their values and protein expressions has been discussed. In addition, the differential proteins in different chemotherapy outcomes have been analyzed. Finally, the potential biomarkers have been detected via enzyme‐linked immunosorbent assay (ELISA). Plasma proteome of 60 CRC patients were profiled. The correlation between plasma protein levels and the results of drug susceptibility testing of CTCs was performed, and 85 proteins showed a significant positive or negative correlation with chemotherapy resistance. Forty‐four CRC patients were then divided into three groups according to their chemotherapy outcomes (objective response, stable disease, and progressive disease), and 37 differential proteins were found to be related to chemotherapy resistance. The overlapping proteins were further investigated in an additional group of 79 patients using ELISA. Protein levels of F5 and PROZ significantly increased in the progressive disease group compared to other outcome groups. Our study indicated that F5 and PROZ proteins could represent potential biomarkers of resistance to chemotherapy in advanced CRC patients.