title: Expression and prognostic value of GalNAc-T3 in patients with completely resected small (≤2 cm) peripheral lung adenocarcinoma after IASLC/ATS/ERS classification.
abstract: BACKGROUND
  GalNAc-T3 catalyzes initial glycosylation of mucin-type O-linked protein involved in proliferation, adhesion, and migration of tumor cells. This study was performed to explore the relationships of the expression of GalNAc-T3 in small peripheral lung adenocarcinoma, especially as an indicator of prognosis.
  
  
  METHODS
  A retrospective analysis of the patients with small peripheral lung lesions, including 106 adenocarcinoma and two precancerous lesions (atypical adenomatous hyperplasia and adenocarcinoma in situ) after complete surgical resection, was launched. Expression of GalNAc-T3 was examined using immunohistochemistry staining on primary tumor specimens, and the tumors were reclassified in light of the IASLC/ATS/ERS (International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society) adenocarcinoma classifications followed by grading and scoring. Moreover, reverse transcription polymerase chain reaction and Western blot were used to study the expression of GalNAc-T3 in vivo.
  
  
  RESULTS
  The low expression of GalNAc-T3 was found in the cytoplasm of tumor cells in 56 of 108 patients (51.9%) and was associated with IASLC/ATS/ERS classification of high risk groups (P=0.007), high Sica score (P=0.036), poorly differentiated tumor (P=0.023), poor tumor-node-metastasis (TNM) stage (P=0.007), pleural invasion (P=0.007), and vascular invasion (P<0.001) by Pearson's chi-squared test, but not with sex, age, smoking status, concentration of carcinoembryonic antigen, and lymph node metastasis. In logistic regression analysis, low GalNAc-T3 expression was only correlated with high-ranking TNM stage (odds ratio [OR] =8.975, 95% confidence interval [CI]: 1.797-44.661), vascular invasion (OR =5.668, 95% CI: 1.827-17.578), and the higher risk grade (low risk grade: OR =0.141, 95% CI: 0.027-0.719; moderate risk grade: OR =0.122, 95% CI: 0.017-40.871). The low expression of the GalNAc-T3 usually in adenocarcinoma cell lines was compared with normal bronchial epithelium cell line. Based on the univariate and multivariate analysis, poor TNM stage (P<0.001), pleural invasion (hazard ratio [HR]: 7.958, P=0.021), vascular invasion (HR: 2.403, P=0.040), and low GalNAc-T3 expression (HR: 3.317, P=0.016) were shown to be independently associated with an unfavorable prognosis. However, IASLC/ATS/ERS classification of risk groups and Sica score (P=0.034 and P=0.032, respectively) was correlated with overall survival on Kaplan-Meier method but not Cox regression model.
  
  
  CONCLUSIONS
  GalNAc-T3 expression was correlated with the IASLC/ATS/ERS classification and also associated with prognosis of patients with completely resected small (≤2 cm) peripheral lung adenocarcinoma.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China ; Lung Cancer Diagnosis and Treatment Center, Dalian, People's Republic of China.
authors.forename: Shilei
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China ; Lung Cancer Diagnosis and Treatment Center, Dalian, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Guo
authors.affiliation: Lung Cancer Diagnosis and Treatment Center, Dalian, People's Republic of China.
authors.forename: Jinxiu
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Saitama Cancer Center, Saitama, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Uramoto
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Guan
authors.affiliation: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, People's Republic of China.
authors.forename: Wuguo
authors.initials: W
authors.lastname: Deng
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China ; Lung Cancer Diagnosis and Treatment Center, Dalian, People's Republic of China.
authors.forename: Chundong
authors.initials: C
authors.lastname: Gu
keywords: GalNAc-T3; classification; lung adenocarcinoma; prognosis