UPLC-MS based urine untargeted metabolomic analyses to differentiate bladder cancer from renal cell carcinoma

Abstract

Purpose To discover biomarker panels that could distinguish cancers(BC & RCC) from healthy controls(HCs) and bladder cancers(BC) from renal cell carcinoma(RCC), regardless of whether with hematuria. Methods Totallys, 403 participants were enrolled in our study, with 146 BC patients(77 without hematuria and 69 with hematuria), 115 RCC patients (94 without hematuria and 21 with hematuria) and 142 gender- and age- matched HCs. Their midstream urine samples were collected and analysed by performing UPLC-MS. The statistical methods and pathway analyses were applied to discover potential biomarker panels and altered metabolic pathways. Results The panel of α-CEHC, β-cortolone, deoxyinosine, flunisolide, 11b,17a,21-trihydroxypreg-nenolone and glycerol tripropanoate could distinguish the cancers from the HCs(the AUC was 0.950) and the external validation also displayed a good predictive ability (the AUC was 0.867). The panel consisiting of 4-ethoxymethylphenol, prostaglandin F2b, thromboxane B3, hydroxybutyrylcarnitine, 3-hydroxyphloretin and N'-formylkynurenine could differentiate BC from RCC without hematuria. The AUC was 0.829 in the discovering group and 0.76 in the external validation. The metabolite panel comprising 1-hydroxy-2-oxopropyl tetrahydropterin, 1-acetoxy-2-hydroxy-16-heptadecyn-4-one, 1,2-dehydrosalsolinol and L-tyrosine could significantly discriminate BC from RCC with hematuria(AUC was 0.913). Pathway analyses revealed there existed alterd lipid and purine metabolism between cancers and HCs, together with disordered amino acid and purine metablism between BC and RCC with hematuria. Conclusions The UPLC-MS urine metabolomic analyses could not only differentiate the cancers from HCs but also discriminate the BC from RCC. Besides, pathway analyses could demonstrate the deeper metabolic mechanism of BC and RCC.

GC-MS based metabolite fingerprinting of serous ovarian carcinoma and benign ovarian tumor

“…It has been frequently emphasized that carbohydrates are the most important metabolites that distinguish cancerous cells from healthy cells. 35–38 In the present study, turanose metabolite differed in OC patients from BT patients ( p = ​​06.58E-04). In a study conducted by Cheng et al ., 12 a group of metabolite markers consisting of maltose, maltotriose, raffinose, and mannitol were determined to differentiate OC from BT with an AUC value of 0.832.…”

“…In a previous study, five biomarkers, including L-tyrosine, were found to be important in the urine samples of bladder cancer group (AUC:0.913). 36 L-tyrosine amino acid was defined as a biomarker showing a significant difference between prostate cancer and HC (p < 0.0001). 39 17 metabolites, including L-tyrosine, were identified as potential biomarkers to differentiate patients with gastric cancer.…”