A Preliminary Study On Prognosis Of Galnac-t3to Forecast Patients With Small Peripheral Lung Adenocarcinoma

Objective:To explore the expression of N-acetyl galactosamine transferase-3(UDP-N-acetyl–alpha-D-galactosamine:polypeptide-N-acetylgalactosaminyltransferase-3)in differentNoguchi classification subtypes of small peripheral lung adenocarcinoma (<2cm), andsimultaneously evaluate the relationship between the GalNAc-T3expression level andprognosis in small peripheral lung adenocarcinoma patients in order to providefoundation of formulating the individualization treatment strategies for high-risk groupsof small peripheral lung adenocarcinoma.Methods:Forty-nine patients with lung adenocarcinoma who underwent complete surgicalresection were collected between January2006and June2009at the First AffiliatedHospital of Dalian Medical University. The criteria for inclusion into the study is thatpatients had not received preoperative chemotherapy or radiotherapy and had resectabletumor diameter<2cm（cut edge without residual tumor cells） and a complete clinicalfollow-up data (gender, age, IASLC/ATS/ERS classification of lung adenocarcinoma,organization pathologic stage and lymphatic, vascular metastasis, and disease-free rawsurvival time and overall survival time and so on). Conventional HE staining was usedfor the primary lung adenocarcinoma which was classified in accordance with theNoguchi classification, and we analyzed the GalNAc-T3status of the primary lungadenocarcinoma specimens by IHC analysis. For the postoperative follow-up, thepatients were examinedevery month within the first year and at approximately2-to4month intervals thereafter.The statistical significance was evaluated using the Table analysis. TheKaplan-Meier method was used to estimate the probability of survival andrecrudescence, and which differences were analyzed by the log-rank test. The Cox proportional hazards model was applied to evaluate independent associations using amultivariate regression logistic. Data was analysed with the use of spss19.0anddifference was considered to be significant at P﹤0.05.Result:The low expression of GalNAc-T3was associated with poorly differentiatedtumour (p=0.034),pleural invasion(p=0.028), lymphatic invasion(p=0.050), vascularinvasion(p=0.001), groups of the IASLC/ATS/ERS histological classification(p=0.006)and Noguchi’s subtypes (p=0.003),but not gender (p=0.154),ages (p=0.212),concentration of CEA (p=0.565) and pTNM (p=0.095).We found expression of GalNAc-T3was not different between subtype A or B andC in small peripheral lung adenocarcinoma(p=0.089), and its significantly differentbetween C and mixed group of D，E and F subtype (p=0.008). Moreover, betweengroups of high and moderate histological classification or moderate and low histologicalclassification had significantly different(respectively p=0.036, p=0.042) in accordingwith groups of the IASLC/ATS/ERS histological classification.The small peripheral lung adenocarcinoma patients with male gender,lowGalNAc-T3expression, poorly differentiated tumour, high pTNM, pleural invasion,vascular invasion， lymphatic invasion, low histological classification or poorlyNoguchi’s subtypes had a early relapse than those without (p﹤0.05), simultaneouslylow GalNAc-T3expression, pleural invasion, low histological classification or poorlyNoguchi’s subtypes had a early mortality than those without(p﹤0.05). In addition,multivariate analysis of the small peripheral lung adenocarcinoma patients indicated thatmale gender （p=0.016，rr=0.250）,the low expression of GalNAc-T3（p=0.006，rr=0.102）,vascular invasion（p=0.049，rr=0.359）, pleural invasion（p=0.012，rr=4.224）were significant independent factors for predicting early recurrence, furthermore thelow expression of GalNAc-T3（p=0.046，rr=0.302）, pleural invasion（p=0.038，rr=0.3.497）, low histological classification（p=0.039，rr=3.008） were significantindependent factors for predicting overall survival.Cell proliferation of the lung adenocarcinoma A549cell line infected with pll3.7-GalNAc-T3lentivirus group after72hours was remarkably descended compared withcontrol group（p=0.017） and lentivirus vector group（p=0.022）. The number of cellsin pll3.7-GalNAc-T3lentivirus group was fewer than control group (p=0.006) andlentivirus vector group (p=0.019)in the Tanswell invasion assay after24hours. Conclusion:The low expression of GalNAc-T3and pleural invasion may be a useful marker forpredicting poor prognosis and early recurrence in small peripheral adenocarcinomaspatients.