Low C24‐OH and C22‐OH sulfatides in human renal cell carcinoma

Abstract

Histopathologic diagnosis of renal cell carcinoma (RCC) may sometimes be difficult with small biopsy samples. We applied histology-directed matrix-assisted laser desorption/ionization mass spectrometry to RCC samples to evaluate whether and how lipid profiles are different between RCC and normal tissue. We evaluated 59 RCC samples and 24 adjacent normal tissue samples collected from patients who underwent surgery. Five peaks were significantly differently expressed (p < 10(-7)) between RCCs and adjacent normal tissue samples. C24-OH sulfatide (ST-OH {18:1/24:0}[M-H](-); m/z 906.7 in the negative ion mode) and C22-OH sulfatide (ST-OH {18:1/22:0}[M-H](-); m/z 878.6 in the negative ion mode) were most significantly underexpressed in RCC samples, compared with adjacent normal tissue samples. With 100 random training-to-test partitions within these samples, the median prediction accuracy (RCC vs. normal) ranged from 96.3% to 100% at p cutoff values for feature selection ranging from 0.001 to 10(-7). Two oncocytoma samples were predicted as normal tissue by five lipids that were differentially expressed between RCC and normal tissue at p < 10(-7). Clear-cell, papillary, and chromophobe RCCs were different in lipid profiles. Permutation p- values for 0.632+ bootstrap cross-validated misclassification rates were less than 0.05 for all the classifiers. Thus, lipid profiles differentiate RCC from normal tissue and may possibly classify the histology of RCC.

Altered Plasma, Urine, and Tissue Profiles of Sulfatides and Sphingomyelins in Patients with Renal Cell Carcinoma

“…In our previous work, we compared 157 tumor and autologous nonmalignant tissues from 80 patients with RCC [19], and reported decreased concentrations of monohexosyl sulfatides (SHexCer) with additional hydroxyl in the ceramide part in the tumor tissue compared to non-neoplastic autologous tissue. These observations are consistent with the results reported by Kim et al [14]. We found elevated levels of sulfatides composed of two hexosyl units (SHex2Cer) in tumor tissues compared to adjacent nonneoplastic tissues.…”

“…Sulfatides participate in adhesion to functional proteins, the maintenance and modification of ion channels, and the induction of cell differentiation [13]. The importance of sulfatide metabolism and sulfotransferase gene expression for the morphological differentiation of tumor and metastatic potentials of colorectal, ovarian, or renal carcinomas has been shown in numerous reports [14][15][16][17][18].…”

“…Significantly altered sulfatide profiles are usually observed in tumor tissues or cells because of the high local concentrations of studied lipids. However, only a few studies have been published on sulfatide analysis in the cells and tissues of RCC patients [14,19]. To the best of our knowledge, no work on the quantitation of sulfatides in body fluids of RCC patients has been reported to date in the literature.…”

Alterations in Lipid Profile Upon Uterine Fibroids and Its Recurrence

“…Shotgun lipidomics based on electrospray ionization mass spectrometry (ESI-MS) allows deep molecular profiling of a sample without significant losses of chemical information [26,27]. The high diagnostic potential of lipidomics has been shown in many areas of medicine, particularly in oncology: lung, thyroid gland, breast, stomach, pancreas, colorectal, liver, kidney, prostate, ovarian, and endometrium cancer [28,29,[38][39][40][41][42][43][44][45][46][47]30,[48][49][50][51][31][32][33][34][35][36][37]. MS studies of lipid profiles in tissues and blood plasma have revealed new promising biomarkers of endometriosis (benign gynecological disorder) [26,27,32,33,37,44,47].…”

Polyunsaturated fatty acid deficiency affects sulfatides and other sulfated glycans in lysosomes through autophagy‐mediated degradation

“…11,12 Several studies have proposed that disturbances in sulfatide metabolism might be associated with such kidney diseases as renal cell carcinoma and polycystic kidney disease. 13,14 Sulfated glycans, currently explored in medicine as glycosaminoglycans (GAGs), are also known to contribute to numerous pathophysiological processes. In the nervous system, GAGs reportedly play many critical roles, including regulation of the proliferation and differentiation of neural progenitor cells, neuronal migration, neural regeneration and plasticity, synaptogenesis, and axon pathfinding.…”