A Novel Diagnostic Biomarker, PZP, for Detecting Colorectal Cancer in Type 2 Diabetes Mellitus Patients Identified by Serum-Based Mass Spectrometry

Background: Growing evidence has confirmed that populations with type 2 diabetes mellitus (T2DM) have an increasing risk of developing colorectal cancer (CRC). Thus, convenient and effective screening strategies for CRC should be developed for the T2DM population to increase the detection rate of CRC. Methods: Twenty serum samples extracted from 5 healthy participants, 5 T2DM patients, 5 CRC patients and 5 T2DM patients with CRC (T2DM+CRC) were submitted to data-independent acquisition mass spectrometry (DIA-MS) analysis to discover unique differentially altered proteins (DAPs) for CRC in patients with T2DM. Then, the diagnostic value of pregnancy zone protein (PZP) was validated by ELISA analysis in the validated cohort. Results: Based on DIA-MS analysis, we found 8 unique proteins specific to T2DM patients with CRC. Among these proteins, 4 proteins showed different expression between the T2DM+CRC and T2DM groups, and PZP exhibited the largest difference. Next, the diagnostic value of serum PZP was validated by ELISA analysis with an AUC of 0.713. Moreover, the combination of PZP, CA199 and CEA exhibited encouraging diagnostic value, and the AUC reached 0.916. Conclusion: Overall, our current research implied that PZP could be regarded as a newfound serum biomarker for CRC medical diagnosis in T2DM patients.