The Study On Relationship Of Hyaluronic Acid And Lung Adenocarcinoma’s Progression

Objection: To explore the relationship between hyaluronidase,hyaluronic acid synthase and CD44,CD147 and CD168 expression in lung adenocarcinoma tissue and the development of lung adenocarcinoma in different clinical stages.Materials and Methods: The expression of hyaluronidase 1-4,hyaluronidase synthase subtypes(HAS1,HAS2,HAS3),CD44,CD147 and CD168 in 50 cases of TNM stage I-III lung adenocarcinoma(patients who underwent surgical resection without history of radiotherapy and chemotherapy)were screened by immunohistochemical method.The expression of hyaluronidase 1-4,hyaluronidase synthase subtypes(HAS1,HAS2,HAS3),CD44,CD147 and CD168 were observed under microscope and photograph Image-Pro plus 6.0 software was used to analyze the image and obtain IOD value.Variance analysis,correlation analysis and regression analysis were carried out with SPSS 22.0 software for the IOD.The function scale was used to standardize the IOD in R language,and hyaluronic acid synthase and hyaluronic acid synthase in different stages were standardized.The average values of the enzymes closely related to the production of hyaluronic acid fragments and the percentiles of 0.8,0.6,0.4 and 0.2 were calculated by the percentile function,and then compared with the average values,so as to obtain a comprehensive evaluation of hyaluronic acid synthase,hyaluronidase and their catalytic effects in various stages.Results: 1.The evaluation of the capacity of hyaluronic acid synthase: the expression of hyaluronic acid synthase was up-regulated in phase IA,and down-regulated rapidly in phase IB,reached a peak in phase IIA,then decreased to bottom,and increased again in phase III.2.The evaluation of the ability of hyaluronidase: the expression of hyaluronidase increased gradually from stage I to III.3.The evaluation of the production of hyaluronic acid fragments: the amount of hyaluronic acid expression increased gradually from stage I to II,and then gradually decreased from stage III,but it was still more than that of stage I.4.The expression profile of HAS 1-3: there was no significant difference of HAS1,among IA,IB,IIA,IIB and |III groups(p>0.05).The expression of HAS2 in group III was significantly higher than that in group IA and IB(p<0.05),and the expression in group IIA and IIB was not significantly different(p>0.05).There was no significant difference between HAS3,IA,IB,IIA,IIB and III groups(p>0.05).5.The expression of hyaluronidase 1-4: there was no significant difference in the expression of hyaluronidase 1 among groups(p>0.05).There was no significant difference in the expression of hyaluronidase 2 between groups IA,IB,IIA,IIB and III(p>0.05).There was no significant difference in the expression of hyaluronidase 3 between groups IA,IB,IIA and IIB(p>0.05).Compared with group IIB,there was a significant difference between group III and group IIB(p<0.05).Compared with the IA group,there was no significant difference in the expression of hyaluronidase 4 between the IB group,IIA group,IIB group and IA group(p>0.05),while there was significant difference between the III group and IA group(p<0.05).Compared with the IB group,there was no significant difference between the IA group,IIA group,IIB group and IB group(p>0.05),while there was significant difference between the III group and IB group(p<0.05).Compared with IIA group,there was no significant difference between IIB group,IA group,IB group and IIA group(p>0.05),while there was significant difference between III group and IIA group(p<0.05).Compared with IIB group,there was no significant difference between IA group,IB group,IIA group and IIB group(p>0.05),while there was significant difference between III group and IIB group(p<0.05).6.The expression profile of hyaluronic acid receptor(CD): CD44 expression in group III was significant difference compared with that in group IA,IB and IIB(p<0.05).The expression of CD147 in group III was significantly higher than that in group IA,IB,IIA and IIB(p<0.05).The expression of CD168 in group III was significant difference compared with that in group IA,IB and IIB(p<0.05),and there was no significant difference compared with that in group IIA(p>0.05).Conclusion: 1.The synthesis of hyaluronic acid precursors was mainly catalyzed by HAS1 and HAS2.The enzyme that changed with TNM stage of lung adenocarcinoma was HAS2.With the development of TNM stage from I to III,the expression of HAS2 increased significantly from I to II,but there was no significant change from II to III.This change was related to the significant increase of hyaluronidase 3 and hyaluronidase 4.2.As the TNM stage increased,the synthesis capacity of hyaluronic acid fragments gradually increased from stage I to stage II,and decreased from stage III,but it was still stronger than that of stage I.The production of hyaluronic acid was mainly composed of HAS1 and 2 isoform composite chain hyaluronic acid precursors,which were then decomposed by hyaluronic acid enzymes into short chain hyaluronic acid fragments to play the role of tumor metastasis.Among them,hyaluronidase 1 and hyaluronidase 4 were the most important decomposing enzymes,and their significant effects ran through stage I,II and III of lung adenocarcinoma.3.The expression of hyaluronidase 1 in lung adenocarcinoma tissues was mainly transmitted to cells through CD147,which promoted the cell proliferation and development of non-small cell lung cancer.Meanwhile,the expression of CD44,CD147 and CD168 was related to TNM stage of lung adenocarcinoma.