Upregulated plasma and urinary levels of nucleosides as biological markers in the diagnosis of primary gallbladder cancer

Abstract

We first detected aberrant nucleoside levels in the plasma, urine, bile, and tissues from cases and controls to explore them as biomarkers in the diagnosis of gallbladder cancer. Reversed-phase high-performance liquid chromatography was used to assess the levels of ten nucleosides in these samples from gallbladder cancer patients, gallstone patients, and healthy controls. Plasma and urine samples were collected from patients with gallbladder cancer (n = 202), patients with gallstones (n = 203), and healthy controls (n = 205); bile and tissue samples were collected from 91 gallbladder cancer patients, 93 gallstone patients; and 90 were donated after cardiac death. Of the ten nucleosides analyzed, eight urinary nucleosides, five plasma nucleosides, three bile nucleosides, and one tissue nucleoside were significantly upregulated in the gallbladder cancer patients compared to control groups (p < 0.05). Among these upregulated nucleosides, the sensitivity, specificity, and accuracy of urinary nucleosides in the diagnosis of gallbladder cancer patients were 89.4, 97.1, and 95.7%, respectively, those of plasma nucleosides were 91.2, 95.6, and 94.2%, respectively, those of bile nucleosides were 95.3, 96.4, and 95.1%, respectively, and those of tissue nucleosides were 86.2, 93.8, and 92.6%, respectively. These results suggest that nucleosides may be as useful as biological markers for gallbladder cancer.

Urine biomarkers in cancer detection: A systematic review of preanalytical parameters and applied methods

“…Proteins, 137 nucleosides 138 and metabolic profiles 139 have been investigated as potential urinary biomarkers for cholangiocarcinoma. Further research is needed to prove their potential.…”

Variants and haplotypes in Flap endonuclease 1 and risk of gallbladder cancer and gallstones: a population-based study in China

“…This result was significantly higher than the percentage of cholelithiasis observed in the healthy control group (6.2%, 21 of 339). Additionally, physical trauma caused by gallstones or bile-containing carcinogens may synergistically induce epithelial dysplasia, encouraging the ultimate progression to carcinoma 46 47 . Our previous study demonstrated that cholelithiasis and cholecystitis produced a series of pathological epithelial changes, including simple epithelial hyperplasia, atypical hyperplasia and carcinoma in situ 47 .…”

“…Additionally, physical trauma caused by gallstones or bile-containing carcinogens may synergistically induce epithelial dysplasia, encouraging the ultimate progression to carcinoma 46 47 . Our previous study demonstrated that cholelithiasis and cholecystitis produced a series of pathological epithelial changes, including simple epithelial hyperplasia, atypical hyperplasia and carcinoma in situ 47 . These pathological changes are all considered precancerous lesions of gallbladder carcinoma 48 49 .…”

Molecular signature of renal cell carcinoma by means of a multiplatform metabolomics analysis

“…Additionally, these metabolites are potential biomarkers of oxidative stress [ 76 ]. The role of nucleosides was confirmed in the development of cancers of the urinary tract [ 77 ], breast [ 78 ], gallbladder [ 79 ] and liver [ 80 ]. In the reported study, elevated levels of uric acid and several nucleosides were observed.…”