The use of matrix coating assisted by an electric field (MCAEF) to enhance mass spectrometric imaging of human prostate cancer biomarkers

Abstract

In this work, we combined a newly developed matrix coating technique - matrix coating assisted by an electric field (MCAEF) and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) to enhance the imaging of peptides and proteins in tissue specimens of human prostate cancer. MCAEF increased the signal-to-noise ratios of the detected proteins by a factor of 2 to 5, and 232 signals were detected within the m/z 3500-37500 mass range on a time-of-flight mass spectrometer and with the sinapinic acid MALDI matrix. Among these species, three proteins (S100-A9, S100-A10, and S100-A12) were only observed in the cancerous cell region and 14 proteins, including a fragment of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 2, a fragment of cAMP-regulated phosphoprotein 19, 3 apolipoproteins (C-I, A-I, and A-II), 2 S100 proteins (A6 and A8), β-microseminoprotein, tumor protein D52, α-1-acid glycoprotein 1, heat shock protein β-1, prostate-specific antigen, and 2 unidentified large peptides at m/z 5002.2 and 6704.2, showed significantly differential distributions at the p < 0.05 (t-test) level between the cancerous and the noncancerous regions of the tissue. Among these 17 species, the distributions of apolipoprotein C-I, S100-A6, and S100-A8 were verified by immunohistological staining. In summary, this study resulted in the imaging of the largest group of proteins in prostate cancer tissues by MALDI-MS reported thus far, and is the first to show a correlation between S100 proteins and prostate cancer in a MS imaging study. The successful imaging of the three proteins only found in the cancerous tissues, as well as those showing differential expressions demonstrated the potential of MCAEF-MALDI/MS for the in situ detection of potential cancer biomarkers. Copyright © 2015 John Wiley & Sons, Ltd.

Prostate cancer diagnosis and characterization with mass spectrometry imaging

“…In a recently published work, endogenous compounds of cancerous and non-cancerous regions in three human prostate cancer tissue specimens were detected and imaged using matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry imaging (MALDI FTICR MSI) 70 . The authors combined two different MALDI matrices (quercetin and 9-aminoacridine) and used the newly developed technique of matrix coating assisted by an electric field (MCAEF) 79 , 80 . A total of 1091 metabolites were identified, of which 250 and 217 were exclusively found in either the cancerous or the non-cancerous regions, respectively.…”

Emerging role of clinical mass spectrometry in pathology

“…A homogeneous coating of matrix with small, uniform matrix crystals of low-micrometre dimensions is desirable. Some techniques that employ this feature are high-throughput electrospray,128 matrix coating assisted by an electric field129 130 and sublimation under vacuum to name a few 131 132. In consideration for rapid clinical application, matrix precoated glass slides were also developed to increase throughput 133 134.…”

Mass spectrometry imaging for &lt;italic&gt;in situ&lt;/italic&gt; analysis of endogenous molecules in plants

“…针 对基质的喷涂方式, 传统喷涂方法包括手动气喷雾 (airbrush) [36] 、电喷雾(electrospray) [37] 、基质升华(sublimation) [38] [41] . 相比于传统常规喷涂方式, 利用该技术可直 接原位表征大约1000多种脂类分子 [40] 、50多种核苷类 /能量代谢相关分子 [40] 、近250种蛋白质分子 [39] , 使得…”