Urine Modified Nucleosides Were Possibly Used As Molecular Marker In Screening The High-risk Population Of Lung Cancer

Objective: Lung cancer is a most common carcinoma of human being. Many patients with lung cancer have reached advanced stage while diagnosed owing to lack of an effective method to find it in early stage. General survey is an effective way of finding lung cancer in early stage. Therefore, it is important to find out a marker which could be used conveniently to screen high-risk population of lung cancer from crowds. Modified nucleosides as main metabolites of tRNA can not be reutilized and they are excreted to urine. The levels of urine modified nucleosides could reflect the metabolic speed of cellular tRNA. The malignant cells have high metabolic speed of RNA, so the cancer patients would excrete more modified nucleosides to their urine than healthy people. Moreover, urine sample collection is convenient and scatheless for examining population. It was reported that the modified nucleosides as a valuable tumor marker had been used in diagnosing leukemia, lymphoma, breast cancer, et al. Therefore, the urine modified nucleosides might become an universal molecular marker of the high-risk population screening of lung cancer. Our study detected the urinary concentrations of pseudouridine (Pseu), 1-methyladenosine (m1A), 1-methylinosine (m1I), 1-methylguanosine (m1G) and 1-methylguanosine (m2G) respectively, and explored the feasibility for them to be markers of high-risk population screening of lung cancer and their relationships with the histological classification and staging of lung cancer.Methods: The concentrations of Pseu, m1A, m1I, m1G and m2G in urine from 55 lung cancer patients, 6 lung benign disease patients and 30 normal adults were detected by high performance liquid chromatography (HPLC) online system. The difference of concentrations of urine modified nucleosides among lung cancer patients, lung benign disease patients and normal adults, and the correlation of the concentration of urine modified nucleosides to the histological classification of lung cancer, and the difference of sensitivities and specificities among combined detection of modified nucleosides were analyzed by SPSS13.0.Results:1. In lung cancer patients, lung benign disease patients and normal adults, the concentrations of Pseu were 33.91±16.50, 27.14±7.49 and 17.87±2.38 nmol/(μmol creatinine) respectively, which was significantly higher in lung cancer group than that in normal group (P=0.000); the concentrations of m1A were 5.29±3.55, 3.91±1.47 and 2.31±0.41 nmol/ (μmol creatinine) respectively, which was significantly higher in lung cancer group than that in normal group (P=0.000); the concentrations of m1I were 2.13±1.52, 1.23±0.42 and 1.08±0.24 nmol/(μmol creatinine) respectively, which was significantly higher in lung cancer group than that in normal group (P=0.000); the concentrations of m1G were 1.07±0.80, 0.50±0.14 and 0.66±0.20 nmol/(μmol creatinine) respectively, which was significantly higher in lung cancer group than that both in lung benign diseases group and in normal group (P=0.04, P=0.005); the concentrations of m2G were 1.04±0.80, 0.72±0.34 and 0.53±0.15 nmol/(μmol creatinine) respectively, which was significantly higher in lung cancer group than that in normal group (P=0.001).2. In the lung cancer patients with squamous carcinoma, small cell lung cancer and adenocarcinoma, the concentrations of m1I were 1.90±0.97, 1.85±1.25 and 2.88±2.22 nmol/(μmol creatinine) respectively, which was significantly higher in the small cell lung cancer group than that in the adenocarcinoma group (P=0.045).3. The contribution to diagnose the lung cancer, from the highest to the lowest would be: m1A, m1I, Pseu, m2G and m1G.4. The sensitivities of Pseu, m1A, m1I, m1G and m2G single detection for diagnosing lung cancer were 81.82%, 85.45%, 61.82%, 45.45% and 58.18% respectively, which of Pseu was significantly higher than that of m1I, m1G and m2G (P=0.020, P=0.000, P=0.007); which of m1A was significantly higher than that of m1I, m1G and m2G (P=0.005, P=0.000, P=0.001).5. The sensitivity of the combined detection of Pseu, m1A and m1I being 98.18% was significantly higher than that of m1A single detection being 85.45% in lung cancer (P=0.037).Conclusions:1. The concentrations of urinary Pseu, m1A, m1I, m1G and m2G in lung cancer patients were significantly higher than those in the healthy adults, which indicated that these modified nucleosides could be used as molecular markers for screening high-risk population of lung cancer.2. The concentration of m1G in lung cancer patients was significantly higher than that in lung benign disease patients, which indicated that detection of m1G might be useful for distinguishing lung cancer from lung benign diseases.3. The concentration of m1I in the small cell lung cancer group was significantly higher than that in the adenocarcinoma group, which indicated that the distribution of urine modified nucleosides might be correlated to classifications in lung cancer patients. So detecting m1I could be helpful for the histological classification of lung cancer.4. The combined detection of m1A, m1I and Pseu can reach the highest sensitivity for lung cancer, which could be used to definite the high-risk group of lung cancer.