| Objective: To compare the difference between serum free glucose/mannose ratio(G/M)and six monosaccharide levels in lung cancer patients and healthy controls,and to explore and analyze the assistant diagnostic value and clinical significance of biomarkers based on glycobiology in lung cancer.Methods: 254 lung cancer patients were hospitalized in the thoracic surgery department of the Affiliated Hospital of Qingdao University from July 1,2018 to June30,2019.254 healthy controls were the people who had health examination in the Affiliated Hospital of Qingdao University at the same time,and their gender and age were corresponding to lung cancer patients.254 patients were divided into pre-operative group and post-operative group according to whether the operation was performed or not,including 102 patients in the pre-operative group and 146 patients in the post-operative group There were 6 cases without relevant information.Fasting venous blood(4 mL)was drawn from both the lung cancer and the healthy control group after admission to the hospital early in the morning,and the blood was centrifuged to obtain the serum,which was subsequently stored in the freezer at-80 ?.First,the standard curve and the regression equation were obtained by using 6monosaccharide standards after labeling with PMP followed by HPLC analysis.Then we obtained HPLC data of both free and hydrolyzed monosacharides from the serum samples of 254 from lung cancer patients and 254 from healthy controls.We calculated the peak area of each monosaccharide and compared the differences in peak areas between the lung cancer patients and healthy controls based on the variance and correlation analyses.The accessory diagnostic value and clinical significance of serum free glucose/mannose ratio(G/M)and hydrolyzed monosaccharide levels in lung cancer patients in comparison to healthy controls such as mannose(Man),glucosamine(GlcN),galactosamine(GalN),glucose(Glc),Galactose(Gal)and fucose(Fuc)were analyzed by ROC curve.Results:(1)The clinical data from 254 lung cancer patients and 254 healthy controls were collected.The data was summarized in Table 1.Statistical analysis indicated that there was no statistical significant difference in the clinical data of the two groups(all P values were >0.05).(2)In the lung cancer group,the G/M value was50.47 ± 21.02,while the control was 77.19 ± 23.59,and based on the statistical analysis,the lung cancer group and the control group had significant difference(P value?0.001).ROC curve analysis found that the G/M value for the area under the curve of lung cancer diagnosis was 0.82,the sensitivity and specificity were 67% and86% respectively,indicating the G/M value had diagnostic value for lung cancer.(3)The G/M values of the preoperative and postoperative lung cancer groups were 60.58± 21.22 and 43.92 ± 17.88,respectively.Based on statistical analysis,there was significant difference between the preoperative group and the postoperative group(P value ? 0.0001).ROC curve analysis demonstated that the AUC of the G/M value between the preoperative and postoperative groups was 0.73,and the sensitivity and specificity were 65% and 72%,respectively,which indicated that there was significant change in G/M value before and after operation.(4)The levels of the five monosaccharides from hydrolyzed sera in lung cancer patients were:(Man=3647 ±808.3,GlcN=4030 ± 1160,Glc=3689 ± 1768,Gal=3287 ± 739.7,Fuc=341.1 ± 92.49),and the levels of the same five monosaccharides from hydrolyzed sera in the healthy control group were(Man=2978±588.9,GlcN=3517±823.4,Glc=3053±1057,Gal=2815±455.5,Fuc=288.3 ± 84.42),which showed that Man,GlcN,Glc,Gal,Fuc from hydrolyzed sera in lung cancer patients were all higher than those in the healthy controls,and the differences were statistically significant(P value<0.001).ROC curve analysis found that the AUCs of the five monosaccharides from hydrolyzed sera for the lung cancer diagnosis were: Man:0.77,GlcN: 0.65,Glc: 0.62,Gal:0.72,Fuc:0.67,with the sensitivity and specificity of Man:65%,79%,GlcN:53%,74%,Glc:54%,65%,Gal:66%,70%,Fuc:65%,61%,respectively.(5)Except for galactosamine,the levels of the other five monosaccharides from hydrolyzed sera in the preoperative lung cancer group were:(Man=3235 ± 846.3,GlcN=3454 ± 1167,Glc=2897 ±1382,Gal=2877 ± 736.6,Fuc=324 ± 98.69),and the levels of the other five monosaccharides from hydrolyzed sera in the postoperative lung cancer group were:(Man=3954±610,GlcN=4454±934.5,Glc=4257±1796,Gal=3592±566.9,Fuc=354.3±84.51).The levels of the five monosaccharides from hydrolyzed sera in the postoperative lung cancer group were higher than that in the preoperative lung cancer group,and the differences were statistically significant(P value<0.001).ROC curve analysis found that the AUC of the five monosaccharides from hydrolyzed sera between preoperative and postoperative geoups were: Man:0.80,GlcN:0.78,Glc:0.77,Gal:0.83,Fuc:0.60,with the sensitivity and specificity of Man:77%,75%,GlcN: 71%,80%,Glc:70%,77%,Gal: 79%,76%,Fuc:50%,67%,respectively,indicating that thefive monosaccharides had significant changes before and after operation(P <0.0001).(6)The levels of five monosaccharides in stage I lung cancer patients were(Man=3625±785,GlcN=4004±1132,Glc=3576±1529,Gal = 3267±717.3,Fuc=334.8±87.52),the levels of five monosaccharides from hydrolyzed sera in stage II lung cancer patients were :(Man=3961 ± 760.9,GlcN=4497 ± 1148,Glc=4750 ± 2723,Gal=3592±717.9,Fuc=384.7±108.8),The levels of the five monosaccharides from hydrolyzed sera in the stage ? lung cancer patients were higher than that in the stage I lung cancer group,and the difference was statistically significant(P<0.001).(7)The levels of five monosaccharides from hydrolyzed sera in patients with lung adenocarcinoma were:(Man=3626 ± 775.2,GlcN=4015 ± 1120,Glc=3672 ±1718,Gal=3265 ± 706.5,Fuc=335.2 ± 87.82),and the levels of five monosaccharides from hydrolyzed sera in patients with lung quamous cell carcinoma were:(Man =4223 ±809.6,GlcN = 4788 ±1264,Glc = 4014 ±1237,Gal = 3853±770.5,Fuc =419.7±106.9),The levels of the five monosaccharides from hydrolyzed sera in the lung quamous cell carcinoma patients were higher than that in the lung adenocarcinoma group,and the difference was statistically significant(P?0.0001).Conclusion: the serum free glucose/mannose ratio(G/M)and hydrolyzed mannose(Man),glucosamine(GlcN),galactosamine(GalN),glucose(Glc),galactose(Gal)and fucose(Fuc)levels between lung cancer patients and healthy controls had significant difference,and might be useful for lung cancer diagnosis in future.Furthermore,TNM staging and classification of lung cancer were correlated with the above five monosaccharide levels.Therefore,the analyses of free and hydrolyzed monosaccharides in sera might be useful for the early diagnosis of lung cancer and also provide a glycobiology tool for monitoring the treatment effects of surgery for lung cancer patients. |
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