Serum N-glycomic Changes In Patients With Lung Cancer And Clinical Application In The Treatment Of Integrated Traditional Chinese And Western Medicine

Objective: To analyze the characteristic expression of serum N-glycome profiles of patients with primary lung cancer,benign lung diseases and healthy control and establish non-invasive diagnostic models for primary lung cancer based on N-glycomics.To explore the clinical value of serum N-sugar chains in the evaluation of prognosis and short-term clinical efficacy of patients with primary lung cancer and it’s correlation with T.C.M.syndrome.And to explore the possible targets of integrated medicine intervention in lung cancer.Methods: In the first part,the peripheral blood of 130 patients with primary lung cancer,77 patients with benign lung diseases and 80 healthy controls were enrolled,the serum N-glycomics were analyzed by the DNA sequencer-assisted,fluorophore-assisted carbohydrate electrophoresis(DSA-FACE).Binomial logistic regression method was used to establish mathematical diagnostic models based on the results of the N-glycograph atlas,and the receiver operating characteristic(ROC)curves were used to evaluate the diagnostic efficacy of the models.Furthermore the N-glycom profiles and mathematical diagnostic models’ relationship between pathological type of lung cancer,TNM staging and serum tumor markers were explored.In part two peripheral blood samples of primary lung cancer patients were collected and the T.C.M.syndrome were determined by the ‘four diagnosis’.The N-glycom profiles were detected in patients with primary lung cancer to explore the relationship between T.C.M.syndromes,pathological types,TNM staging and serum tumor markers.In the third part,56 patients with stage III-IV primary lung cancer were treated by traditional Chinese medicine combined with chemotherapy or targeted therapy.The shortterm clinical efficacy,the changes of serum N-glycom profiles and serum tumor markers were evaluated before and after treatment to clarify the clinical efficacy of N-glycograph and diagnostic model in lung cancer patients and to explore the possible targets of integrated medicine intervention.Results: 1.The N-glycom profiles showed Peak 2,3,4,5,6,9,10,11,12 and Sum Fuc were different in primary lung cancer,benign lung diseases and healthy controls(P<0.05).From the healthy control to the benign lung diseases and to the primary lung cancer patients,Peak2,Peak5,Peak9 showed a gradual upward trend,while Peak3,Peak4,Peak6 and Sum Fuc showed a gradual downward trend.2.Based on the profile of N-glycome,LCtest A was set up to distinguish primary lung cancer from non-lung cancer,LCtest B was set up to distinguish primary lung cancer from benign lung diseases,while LCtest C was set up to distinguish primary lung cancer from healthy control.The area under the ROC curve of LCtest A was 0.728(95%CI:0.670-0.787)which was bigger than that of CEA 0.587(95%CI:0.517-0.658).The area under the ROC curve of LCtest B was 0.791(95%CI:0.728-0.854)which was bigger than that of CEA0.603(95%CI:0.527-0.680).The area under the ROC curve of LCtest C was 0.868(95%CI:0.820-0.917)which was bigger than that of CEA 0.573(95%CI:0.497-0.649).The sensitivity and accuracy of LCtest A,LCtest B and LCtest C was higher than CEA,but the specificity was lower than CEA.The values of LCtest A,LCtest B and LCtest C were the highest in the primary lung cancer group.The level of LCtest A and LCtest C showed a gradual increase trend from healthy controls to benign lung diseases in primary lung cancer.3.There were relationships between N-glycome profiles,diagnostic models,TNM staging and tumor markers in primary lung cancer patients.Peak3,Peak4,Peak6,Peak7 and Sum Fuc were negatively correlated with lung cancer staging,while Peak5,Peak9,Peak12,LCtest A and LCtest C were positively correlated with TNM staging.Peak3,Peak4,Peak6 and Sum Fuc were negatively correlated with CEA.Peak5,Peak9,Peak12 and LCtest C were positively correlated with CEA.There was no statistically significant difference between the N-glycome profiles and the diagnostic models in different pathological types of primary lung cancer(P>0.05).4.With the progression of TNM staging in primary lung cancer group,the proportion of Qi deficiency and phlegm-dampness syndrome decreased,while the proportion of Qi and Yin deficiency syndrome increased.The N-glycome profiles and diagnostic models had statistically significant differences in patients with different syndrome,but there was no statistical difference between the pathology and serum tumor markers(P>0.05).Peak1,Peak6 and Sum Fuc showed a gradual downward trend from Qi deficiency and phlegm-dampness syndrome,deficiency yin and excessive heat syndrome to Qi and Yin deficiency syndrome.Peak5,Peak11 and LCtest B value showed a gradual upward trend among the those syndromes.5.56 patients with primary lung cancer of Ⅲ-Ⅳ stage were treated with integrated traditional Chinese and western medicine for one month.51 cases were with stable disease and 5 cases with progressive disease.After treatment Peak3 was significantly higher than before treatment(P<0.05),but there was no significant difference in serum tumor marker before and after treatment(P>0.05).After treatment,Peak3 in the stable disease group was significantly higher than before treatment(P<0.05),while there was no statistical difference in the N-glycome profiles before and after treatment in the progressive disease group(P>0.05).After the treatment of T.C.M.combined with chemotherapy,Peak3 and Sum Fuc were significantly higher than before treatment while Peak5 was significantly lower than before treatment(P<0.05).There was no statistical difference in serum tumor markers before and after treatment(P>0.05).Conclusion: 1.The serum N-glycome profiles of the primary lung cancer patients changed distinguishably when compared with those of benign lung diseases and healthy controls.The N-glycome profiles have potential application value in screening and diagnosis of primary lung cancer.2.Compared to CEA,the non-invasive diagnostic models based on N-glycome profiles have higher sensitivity and accuracy in the screening of primary lung cancer.3.The N-glycome profiles of peripheral blood are correlated with TNM staging,T.C.M.syndrome and short-term clinical efficacy in patients with primary lung cancer.4.The integrated traditional Chinese and Western medicine treatment can affect the Peak3 in the peripheral blood N-glycome profiles of patients with primary lung cancer,but it still needs prospective studies to verify it.