In situ biomarker discovery and label-free molecular histopathological diagnosis of lung cancer by ambient mass spectrometry imaging.

Tiegang Li,Mingrong Wang,Ying Bi,Xin Xu,Xiaohao Wang,Jie Chen,Chengan Guo,Fei Tang,Zeper Abliz,Zhigang Luo,Xinxin Mao,Jiuming He

doi:10.1038/srep14089

Abstract

Sensitive and spatial exploration of the metabolism of tumors at the metabolome level is highly challenging. In this study, we developed an in situ metabolomics method based on ambient mass spectrometry imaging using air flow-assisted desorption electrospray ionization (AFADESI), which can spatially explore the alteration of global metabolites in tissues with high sensitivity. Using this method, we discovered potential histopathological diagnosis biomarkers (including lipids, amino acids, choline, peptides, and carnitine) from 52 postoperative lung cancer tissue samples and then subsequently used these biomarkers to generate images for rapid and label-free histopathological diagnosis. These biomarkers were validated with a sensitivity and a specificity of 93.5% and 100%, respectively. Moreover, a single imaging analysis of a cryosection that visualized all these biomarkers, taking tens of minutes, revealed the type and subtype of the cancer. This method could potentially be used as a molecular pathological tool for rapid clinical lung cancer diagnosis and immediate image-guided surgery.

Highlights

Conditions[8,9,10,11,12]
We developed an in situ metabolomics method based on the ambient air flow-assisted desorption electrospray ionization (AFADESI)-Mass spectrometry imaging (MSI) technique and multivariate statistical analysis (MVSA), with the aim of simultaneously exploring the spatial distribution of all unknown metabolites under a pathological state within a tissue sample
These results suggested that AFADESI-MSI has the ability to acquire multiple types of in situ information about endogenous metabolites from tissues, with high sensitivity and broad metabolite coverage

Summary

Introduction

Conditions[8,9,10,11,12]. Metabolomics—the study of the entire set of small-molecule metabolites present in a biological sample—is widely used to identify and evaluate potential diagnostic biomarkers in a variety of malignancies[13,14]. We recently developed a novel air flow-assisted desorption electrospray ionization (AFADESI) that uses high-rate air flow to enhance ion transmission and ionization efficiency under ambient conditions. Using this technique, we successfully achieved rapid real-time monitoring[28] and whole-body molecular imaging of a known anticancer agent[29]. We developed an in situ metabolomics method based on the ambient AFADESI-MSI technique and multivariate statistical analysis (MVSA), with the aim of simultaneously exploring the spatial distribution of all unknown metabolites under a pathological state within a tissue sample. When the in situ metabolomics method based on AFADESI-MSI was applied to the histological diagnosis of lung cancer, the results demonstrated that this method is effective and feasible

Methods

Results

Conclusion