Plasma lipidomic profiles of kidney, breast and prostate cancer patients differ from healthy controls

Abstract

Early detection of cancer is one of the unmet needs in clinical medicine. Peripheral blood analysis is a preferred method for efficient population screening, because blood collection is well embedded in clinical practice and minimally invasive for patients. Lipids are important biomolecules, and variations in lipid concentrations can reflect pathological disorders. Lipidomic profiling of human plasma by the coupling of ultrahigh-performance supercritical fluid chromatography and mass spectrometry is investigated with the aim to distinguish patients with breast, kidney, and prostate cancers from healthy controls. The mean sensitivity, specificity, and accuracy of the lipid profiling approach were 85%, 95%, and 92% for kidney cancer; 91%, 97%, and 94% for breast cancer; and 87%, 95%, and 92% for prostate cancer. No association of statistical models with tumor stage is observed. The statistically most significant lipid species for the differentiation of cancer types studied are CE 16:0, Cer 42:1, LPC 18:2, PC 36:2, PC 36:3, SM 32:1, and SM 41:1 These seven lipids represent a potential biomarker panel for kidney, breast, and prostate cancer screening, but a further verification step in a prospective study has to be performed to verify clinical utility.

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

“…For example, SM 41:1;O2 and SM 42:1;O2 are downregulated in both sample matrices, while lower levels of multiple other SM are observed in plasma rather than in the tumor tissue. Reduced levels of SM in RCC have been documented before [11,43], and these findings suggest that SM levels and alteration of the synthetic and degradative pathways play an essential role in cancer. It was reported that SM accumulate in the HCT-116 (human colon cancer cell lines) during apoptosis [44].…”

“…Solvents for extraction were purchased from Sigma-Aldrich (St. Louis, MI, USA). For lipid extraction from 25 µL of plasma, a modified Folch method with a chloroformmethanol-water mixture was employed [11]. The samples were spiked before extraction with a mixture of internal standards obtained from Avanti Polar Lipids (Alabaster, AL, USA) to achieve final concentrations of 0.1 nmol of SHexCer 18:1;O2/12:0 and 43.3 nmol of SM 18:1;O2/12:0 per mL of plasma.…”

“…Reliable lipidomics can serve as support for the detection of cancer [7], the elucidation of biochemical mechanisms associated with tumor growth [8], and the development of new drugs [9]. For example, sphingomyelins, together with ceramides, phospholipids, and glycerolipids, have shown the potential to detect kidney, breast, pancreatic, and prostate cancer [10,11]. Sulfatides, a class of low-abundance sphingolipids, seem to be a good target for such research as well [12].…”

Lipid Biomarkers in Liquid Biopsies: Novel Opportunities for Cancer Diagnosis

“…Levels of ethanolamine-containing phospholipids, including PEs, LPEs and PE plasmalogens, were significantly low in four cancer types but high in thyroid cancer, thus reinforcing the idea that plasma lipidomics may reveal features common to different types of cancer, as well as cancer-specific features. Wolrab et al investigated the plasma lipidomic profiles of breast, kidney and PCa patients, finding that the most significant lipid species for cancer separation were CE 16:0, Cer 42:1, LPC 18:2, PC 36:2, PC 36:3, SM 32:1, and SM 41:1, all down-regulated in the plasma of patients as compared to controls, thus representing a potential biomarker panel for breast, kidney and PCa screening [ 74 ].…”

Comprehensive characterization of complex glycosphingolipids in human pancreatic cancer tissues

“…Furthermore, GSL with blood group determinants is well known to be synthesized at high levels in the pancreas ( 20 ). Aberrant expression of GSL including alterations in the composition and concentrations of GSL and lipids is a typical hallmark of a wide range of cancers ( 7 , 14 , 21 , 22 , 23 , 24 , 25 ), which has been extensively documented in cancer cell lines ( 22 , 26 , 27 , 28 , 29 ) or tissues ( 20 , 24 , 30 , 31 , 32 , 33 , 34 ) and also reported in body fluids of cancer patients ( 35 , 36 , 37 , 38 ). Several of the studies mentioned above concluded that the reported dysregulation of lipid metabolism in cancer cells is relevant to distinguish cancer patients from healthy controls, suggesting that changes in lipidomes are strongly associated with cancer progression ( 6 ).…”