| Objective:To detect the content of free monosaccharides and degraded monosaccharides in the serum of colorectal cancer(CRC)patients and the monosaccharides in tumor tissues and adjacent tissues,and to explore the diagnostic value of serum monosaccharide markers for colorectal cancer.Methods:1.Evaluation of the diagnostic performance of CEA and CA19-9: The CEA content in serum of 4513 CRC patients confirmed by surgery and pathology and 2757 healthy volunteers in affiliated hospital of Qingdao University from January 2013 to January 2018 was analysed by receiver operating characteristic(ROC)curve;At the same time,the serum CA19-9 content of 4166 of the above 4513 CRC patients and 930 of the above 2757 healthy volunteers were analyzed by ROC curve to evaluate their diagnostic performance.2.Sample collection and grouping: The retrospective cohort of this experiment enrolled a total of 414 patients with serum samples(CRC=148,adenoma=121,healthy control=145),randomly divided into a model group(n=324)and retrospective verification Group(n=90).In addition,53 patients(CRC=25,healthy control=28)were recruited as prospective cohort.In the retrospective model group,47 patients collected serum samples and corresponding tumor tissues and adjacent tissues.In the retrospective cohort,serum samples of 11 patients were collected preoperatively and 1 week postoperatively according to the availability of samples.Serum samples of 30 patients 3 months after surgery were collected outside the aforementioned cohort.3.Instruments and methods for the determination of monosaccharides: the use of highperformance liquid chromatography(HPLC)and high-performance anion exchange chromatography-pulse amperometric detection(HPAEC-PAD)to determine the content of monosaccharides in serum and tissues.4.Statistical methods: t-test,Mann-Whitney U test or Kruskal-Wallis test,Pearson correlation analysis,Logistic regression analysis,etc.Results:1.Clinical data analysis showed that the area under the diagnostic curve(AUC)of CEA was 0.7059 with an accuracy of 61.90%;the AUC of CA19-9 was 0.6176 with an accuracy of 56.04%.2.Serum free monosaccharide and degraded monosaccharide(content)levels: free monosaccharide in serum of CRC patients: glucose(Glc-F)4399.3(3533.8-5317.9)umol / L,mannose(Man-F))89.7(60.2-120.7)umol / L.Degraded monosaccharides: fucose(Fuc-D)147.1(98.04-191.5)umol / L;galactosamine(GalN-D)174.8(140.1-218.1)umol / L;glucosamine(GlcN-D)2558.1(2197.6-2992.4)umol / L;galactose(Gal-D)1846.7(1427.9-2229.2)umol / L;glucose(Glc-D)3797.1(3154.0-5703.9)umol / L and mannose(Man-D)2490.8(1937.3-2812.0)umol / L.The free monosaccharides in the serum of healthy control group: glucose(Glc-F)3946.5(3133.1-4566.5)umol / L;mannose(ManF)55.1(45.7-65.2)umol / L.Degraded monosaccharides: fucose(Fuc-D)105.0(76.1-138.0)umol / L;galactosamine(GalN-D)138.2(106.0-171.6)umol / L;glucosamine(GlcN-D)1915.0(1575.9-2790.1)umol / L;galactose(Gal-D)1364.7(1124.4-1484.6)umol / L;glucose(Glc-D)2630.1(1873.0-3141.7)umol / L and mannose(Man-D)1487.6(1232.5-1947.4)umol / L.The results showed that the two free and six degraded monosaccharides in the serum of CRC patients were significantly higher than those in the healthy control group(P <0.05).3.The logaistic regression analysis of various serum monosaccharides was used to construct CRC diagnosis models,which were respectively called GF1 and GF2.GF1 was used for the diagnosis of CRC,and GF2 was used for the diagnosis of colorectal adenoma.The area under the curve of GF1 was 0.9403,and the accuracy was 91.34%,which was higher than the diagnostic performance of CEA and CA19-9(P <0.05);the area under the curve of GF2 was 0.8025,and the accuracy was 78.04%.4.The diagnostic accuracy of GF1 in the retrospective validation group and prospective cohort were 88.00% and 81.13%,respectively.The diagnostic accuracy of GF2 in the retrospective verification group was 82.61%.5.Comparison of serum monosaccharides in patients with CRC before and one week after surgery: There was no significant difference in GF1 value(P> 0.05).Fifteen(50%)of 30 CRC patients who were followed up 3 months after surgery had negative GF1 values.6.Degraded monosaccharide content of tumor tissue: Fuc-D: 0.037(0.023-0.055)mg / g;GalN-D: 0.110(0.088-0.145)mg / g;GlcN-D: 0.340(0.264-0.424)mg / g;Gal-D: 0.273(0.225-0.308)mg / g,Glc-D: 0.188(0.135-0.263)mg / g and Man-D: 0.186(0.149-0.221)mg / g.Degraded monosaccharide content in adjacent tissues: Fuc-D: 0.018(0.014-0.024)mg / g;GalN-D: 0.058(0.046-0.074)mg / g;GlcN-D: 0.234(0.175-0.306)mg / g;Gal-D: 0.198(0.159-0.227)mg / g,Glc-D: 0.203(0.149-0.286)mg / g and Man-D: 0.127(0.105-0.146)mg / g.The results showed that except for Glc-D,the contents of fucose,galactosamine,glucosamine,galactose,and mannose in tumor tissues were higher than those in adjacent tissues(P <0.05).Correlation analysis of tumor monosaccharide content and serum monosaccharide content showed no significant correlation between the two(P> 0.05).Conclusion:1.The levels of free monosaccharides and degraded monosaccharides in serum of patients with CRC are higher than those in healthy controls.2.The diagnostic model GF1 based on serum monosaccharide content has better diagnostic value for CRC than CEA and CA19-9.The diagnostic model GF2 has certain diagnostic value for colorectal adenoma.3.The content of degraded monosaccharides except glucose in tumor tissues was higher than that in adjacent tissues,and the content of glucode was lower than that in adjacent tissues.There was no significant correlation between serum degraded monosaccharide content and tumor tissue degraded monosaccharide content in CRC patients. |
PDF Full Text Request