Abstract
Infrared (IR) laser ablation-remote-electrospray ionization (LARESI) platform coupled to a tandem mass spectrometer (MS/MS) operated in selected reaction monitoring (SRM) or multiple reaction monitoring (MRM) modes was developed and employed for imaging of target metabolites in human kidney cancer tissue. SRM or MRM modes were employed to avoid artifacts that are present in full scan MS mode. Four tissue samples containing both cancerous and noncancerous regions, obtained from three patients with renal cell carcinoma (RCC), were imaged. Sixteen endogenous metabolites that were reported in the literature as varying in abundance between cancerous and noncancerous areas in various human tissues were selected for analysis. Target metabolites comprised ten amino acids, four nucleosides and nucleobases, lactate, and vitamin E. For comparison purposes, images of the same metabolites were obtained with ultraviolet (UV) desorption/ionization mass spectrometry imaging (UV-LDI-MSI) using monoisotopic silver-109 nanoparticle-enhanced target (109AgNPET) in full-scan MS mode. The acquired MS images revealed differences in abundances of selected metabolites between cancerous and noncancerous regions of the kidney tissue. Importantly, the two imaging methods offered similar results. This study demonstrates the applicability of the novel ambient LARESI SRM/MRM MSI method to both investigating and discovering cancer biomarkers in human tissue.
Highlights
Kidney cancer accounts for 2.2% of the total worldwide cancers and is the third most common cancer of the urinary tract after prostate and bladder cancer, whether measured by incidence or prevalence
The aim of this study is to report the development of new experimental mass spectrometry imaging (MSI) setup referred to as “laser ablation-remoteelectrospray ionization” (LARESI) and to present unique MS imaging results of human tissue, that is, to demonstrate laser ablation-remote-electrospray ionization (LARESI) selected reaction monitoring (SRM) targeted MSI experiments utilizes tandem mass spectrometry (MS/MS) imaging of frozen kidney tissue containing cancerous and noncancerous regions
LARESI experimental setup was tested in order to provide data on variability of pixel-to-pixel MS/MS signal intensity
Summary
Kidney cancer accounts for 2.2% of the total worldwide cancers and is the third most common cancer of the urinary tract after prostate and bladder cancer, whether measured by incidence or prevalence. More than 50% of RCC’s are diagnosed incidentally, and approximately one-third of patients have metastatic tumors beyond the kidney at the time of diagnosis.[3] the most effective treatment for localized RCC is radical nephrectomy with nephron-sparing surgery at an early stage, even after such optimal surgery, nearly one-third of patients experience disease recurrence after surgical resection.[4] Various RCC biomarkers, most of which are proteins, (C-reactive protein (CRP), PTEN, carbonic anhydrase IX (CAIX), hypoxia-inducible factors (HIF-1α and HIF-1β), vascular endothelial growth factor (VEGF, CD44, Ecadherin, osteopontin, antigen Ki-67, and tumor protein p53) have been proposed, and their monitoring might promote timely prognosis of metastatic RCC. Further research to identify new RCC biomarkers is required for early detection, diagnosis, treatment guidance and assessment, monitoring of treatments, identifying relapses, as well as elucidation of molecular processes behind the disease states.[5]
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