Discovery and validation of PZP as a novel serum biomarker for screening lung adenocarcinoma in type 2 diabetes mellitus patients

Jiayue Yang,Shugao Ye,Le Ban,Cuiping Cao,Jie Mei,Wenjun Wu,Zhen Tian,Hong Shen,Cheng Yang,Qinghua Xu,Xin Tong

doi:10.1186/s12935-021-01861-8

Jiayue Yang, Shugao Ye + Show 9 more

Open Access

https://doi.org/10.1186/s12935-021-01861-8

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Abstract

BackgroundPatients with type 2 diabetes mellitus (T2DM) have an increased risk of suffering from various malignancies. This study aimed to identify specific biomarkers that can detect lung adenocarcinoma (LAC) in T2DM patients for the early diagnosis of LAC.MethodsThe clinical information of hospitalized T2DM patients diagnosed with various cancers was collected by reviewing medical records in Wuxi People’s Hospital Affiliated to Nanjing Medical University from January 1, 2015, to June 30, 2020. To discover diagnostic biomarkers for early-stage LAC in the T2DM population, 20 samples obtained from 5 healthy controls, 5 T2DM patients, 5 LAC patients and 5 T2DM patients with LAC (T2DM + LAC) were subjected to sequential windowed acquisition of all theoretical fragment ion mass spectrum (SWATH-MS) analysis to identify specific differentially-expressed proteins (DEPs) for LAC in patients with T2DM. Then, these results were validated by parallel reaction monitoring MS (PRM-MS) and ELISA analyses.ResultsLung cancer was the most common malignant tumor in patients with T2DM, and LAC accounted for the majority of cases. Using SWATH-MS analysis, we found 13 proteins to be unique in T2DM patients with early LAC. Two serum proteins were further validated by PRM-MS analysis, namely, pregnancy-zone protein (PZP) and insulin-like growth factor binding protein 3 (IGFBP3). Furthermore, the diagnostic values of these proteins were validated by ELISA, and PZP was validated as a novel serum biomarker for screening LAC in T2DM patients.ConclusionsOur findings indicated that PZP could be used as a novel serum biomarker for the identification of LAC in T2DM patients, which will enhance auxiliary diagnosis and assist in the selection of surgical treatment at an early stage.

Highlights

Patients with type 2 diabetes mellitus (T2DM) have an increased risk of suffering from various malignancies
Using SWATH-Mass spectrum (MS) and parallel reaction monitoring MS (PRM-MS) analyses, we discovered and preliminarily validated pregnancy zone protein (PZP) and insulin-like growth factor binding protein 3 (IGFBP3) as potential biomarkers
The following two cohorts were used to discover and validate biomarkers (Fig. 1a): In the discovery set, a total of 20 serum samples from 5 healthy controls, 5 T2DM patients, 5 lung adenocarcinoma (LAC) patients at TNM stage 1 and 5 T2DM patients with LAC at TNM stage 1 (T2DM + LAC), which were submitted to SWATHMS analysis; besides, 20 serum samples from T2DM patients and 20 serum samples from T2DM patients with LAC at TNM stage 1 were submitted for PRM-MS and ELISA analysis

Summary

Introduction

Patients with type 2 diabetes mellitus (T2DM) have an increased risk of suffering from various malignancies. Diabetes mellitus occurs when the body cannot produce enough insulin or use insulin effectively. The former is defined as type 1 diabetes mellitus (T1DM), and the latter is type 2 diabetes mellitus (T2DM) [2]. Increasing evidence supports a direct association between T2DM and cancer with higher risks of cancer morbidity and mortality, especially for some of the most common malignancies [7]. Despite the higher risk of cancer morbidity in the T2DM population, reliable biomarkers for screening and early diagnosis of specific types of cancer in T2DM patients have not yet been discovered

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