Detection Of Tumor - Associated Metabolite Profiles In Situ By Mass Spectrometry

As we all know, cancer is a leading cause of death and economic loss in the world. Researches toward this disease have lasted many years, but its developments are just depended on some traditional techniques. Currently, mass spectrometry imaging (MSI) as an emerging technology has been applied in many areas, and its ability of direct detecting multiple compounds without a priori knowledge may open a new gate for cancer mechanism research and diagnosis of tumor. In this study, we employed matrix-assisted laser desorption/ionization fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS) to study the distributions of metabolites on tumor tissues in order to find biomarkers with diagnosibility and the change trend of metabolites in the cancer microenvironment.1. Comprehensive use of tissue imaging and serum lipid profiling to find a panel of lipids with diagnostic capacity on thyroid cancerChanges in serum lipidome and in tissue lipidome are associated with cancer. In this study, tissue imaging and serum lipid profiling were simultaneously performed to investigate changed lipids in both throid tumor tissue and serum.36 thyroid tissues and 289 serum samples from malignant, benign cancer patients and normal participants were used. Multivariate statistical analysis coupled with ion images revealed that the levels of ten lipids (3 phosphatidylcholines,6 phosphatidic acids and 1 sphingomyelin) from tissue and sera are significantly changed in malignant, benign patients and normal indiciduals. Receiver operating characteristic (ROC) curve indicated that the panel of PC (34:1), SM (34:1) and PA (36:3) had an excellent diagnostic ability in serum samples from thyroid cancer patients.2. In situ analysis of the changes of lipids in six types of cancer with mass spectrometry imagingSix different types of cancer(i.e., breast, lung, colorectal, esophageal, gastric, and thyroid cancer) have high rates of incidence or mortality in the world. Previous studies have noted that the activation of de novo lipogenesis is an early and common event in the cancer microenvironment. In this study, we performed lipid imaging and profiling for 134 tissue samples from six different types of cancer using MALDI-FTICR MS, with 2,5-dihydroxybenzoic acid (DHB) and 1,8-bis(dimethyl-amino)naphthalene (DMAN) as matrices in the positive and negative ion modes, respectively. Ion images coupled with multivariate statistical results revealed that the levels of monounsaturated fatty acids and phosphorylcholines were significantly higher in the cancerous areas, whereas levels of polyunsaturated fatty acids and phosphorylcholines were decreased in the same region. The immunohistochemical assay indicated that fatty acid synthase, stearoyl-CoA desaturase-1, and choline kinase a were up-regulated in the cancer micro-environment compared with the adjacent normal tissue. Our findings suggest that de novo lipogenesis was activated in six types of cancer to promote a biosynthesis of lipids with monounsaturated acyl chains and to suppress a biosynthesis of polyunsaturated lipids in the cancer microenvironment.3. Development of the electric field-assisted matrix coating method to study the distributions of small molecular metabolites on clinical cancer tissuesSmall molecule metabolites (SMMs, typically< 500Da) are important cellular constituents which closely associated with tumor development and progression. However, in situ label-free detection of tissue SMMs has been limited due to interference from matrix and/or low sensitivity. Herein, we develop an electric filed-assisted scanning-spraying (EFASS) matrix coating system to deposit matrix on tissue with small crystal sizes, followed by MALDI MSI in negative ion mode. A comparison with other two matrix deposition methods (i.e., airbrush and sublimation) indicated that the EFASS system could effectively enhance detection sensitivity and the number of tissue SMMs detected. Based on the established matrix application method, we performed MSI on gastric cancer tissues. A significant increase of monounsaturated fatty acids (palmitic acid and oleic acid) and nucleosides monophosphate (uridine monophosphate, adenosine monophosphate, and guanosine monophosphate) coupled with a reduce of nucleosides (inosine, guanosine, and uridine) and N-acetylneuraminic acid were first observed in cancerous areas by MSI.