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

Abstract

Purpose: RCC, the most common type of kidney cancer, is associated with high mortality. A non-invasive diagnostic test remains unavailable due to the lack of RCC-specific biomarkers in body fluids. We have previously described a significantly altered profile of sulfatides in RCC tumor tissues, motivating us to investigate whether these alterations are reflected in collectible body fluids and whether they can enable RCC detection. Methods: We collected and further analyzed 143 plasma, 100 urine, and 154 tissue samples from 155 kidney cancer patients, together with 207 plasma and 70 urine samples from 214 healthy controls. Results: For the first time, we show elevated concentrations of lactosylsulfatides and decreased levels of sulfatides with hydroxylated fatty acyls in body fluids of RCC patients compared to controls. These alterations are emphasized in patients with the advanced tumor stage. Classification models are able to distinguish between controls and patients with RCC. In the case of all plasma samples, the AUC for the testing set was 0.903 (0.844–0.954), while for urine samples it was 0.867 (0.763–0.953). The models are able to efficiently detect patients with early- and late-stage RCC based on plasma samples as well. The test set sensitivities were 80.6% and 90%, and AUC values were 0.899 (0.832–0.952) and 0.981 (0.956–0.998), respectively. Conclusion: Similar trends in body fluids and tissues indicate that RCC influences lipid metabolism, and highlight the potential of the studied lipids for minimally-invasive cancer detection, including patients with early tumor stages, as demonstrated by the predictive ability of the applied classification models.

Infrared Spectroscopy of Urine for the Non-Invasive Detection of Endometrial Cancer

“…The advantage of peptides excreted in urine lies in their reduced complexity and higher stability compared to blood plasma proteins, rendering them ideal substrates for biomarker identification [ 45 ]. Increased concentrations of urinary lipids have been identified in renal and prostate cancer patients, and these effects may be present in endometrial cancer as well [ 46 , 47 ]. Increased levels of urinary nucleic acids may reflect the unconstrained proliferation of cells in malignant states, and significantly higher expression (up to 30 fold) has been identified in urinary exosomes isolated from endometrial cancer patients compared to controls [ 48 ].…”

Chewing the fat: How lipidomics is changing our understanding of human health and disease in 2022

“…Bibliometric analyses of clinical lipidomics publications in 2022 using Scopus search terms “lipidomics” AND “clinic*” on 15 th December 2022 …”

“…[170][171][172][173] Lipidomic analyses have revealed cancer-specific lipid dysregulations that could potentially serve as promising biomarkers for screening purposes, 174,175 as demonstrated by Lee et al in a plasma analysis of 140 human samples that could differentiate five cancers (liver, lung, gastric, colorectal, and thyroid). 176 It is therefore of no surprise with its known lipid dysregulation and urgency that oncology was the biggest application area in 2022, where the following cancers were studied: bladder, 177 brain, 155 breast, [178][179][180][181][182] colorectal, [183][184][185][186][187][188] endometrial, 189 gallbladder, 190 gastric, 191 kidney, 192 liver, [193][194][195][196][197] lungs, 156,[198][199][200] nasopharyngeal, 201 ovarian, 202 paediatric, 203 prostate, 204,205 and skin. 206 To maximize the survival rates of cancer patients, it is important to identify cancer at its early stages, where tumours can be surgically removed or treated with milder drug regimens.…”

Lipids as Targets for Renal Cell Carcinoma Therapy

“…Moreover, lactosyl- and galactosylceramide sulfate are markedly increased in RCC as compared to healthy tissue, accompanied by significantly elevated activities of their respective sulfotransferases [ 53 , 54 ]. This is also reflected in the plasma and urine of RCC patients, where elevated concentrations of lactosylsulfatides were stage-dependent and more emphasized in late-stage RCC [ 55 ]. Nevertheless, Porubsky et al (2021) could not confirm an association between CST expression and malignant clinical behavior of RCC [ 56 ].…”