title: Significant correlation between urinary N(1), N(12)-diacetylspermine and tumor invasiveness in patients with clinical stage IA non-small cell lung cancer.
abstract: BACKGROUND
  To select optimal candidates for limited lung resection, it is necessary to accurately differentiate the non-invasive tumors from other small-sized lung cancer. Urinary N(1), N(12)-diacetylspermine (DiAcSpm) has been reported to be a useful tumor marker for various cancers. We aimed to examine the correlation between preoperative urinary DiAcSpm levels and specific clinicopathological characteristics such as the histological tumor invasiveness in patients with clinical stage IA non-small cell lung cancer (NSCLC).
  
  
  METHODS
  We defined non-invasive tumors as NSCLC showing no vascular invasion, lymphatic permeation, pleural invasion, or lymph node metastasis. Preoperative urine samples were obtained from 516 consecutive patients with NSCLC resected at our institution between April 2008 and January 2013. Urinary DiAcSpm values were determined for all preoperative urine samples using the colloid gold aggregation procedure. Among these patients, 171 patients with clinical stage IA NSCLC met the criteria of our study cohort. Finally, we investigated the correlation between non-invasive tumor and urinary DiAcSpm levels.
  
  
  RESULTS
  The median urine DiAcSpm for males was 147.2 nmol/g creatinine and 161.8 nmol/g creatinine in females. These median values were set as the cut-off values for each gender. Patients with higher urinary DiAcSpm levels frequently had significantly elevated serum CEA (p = 0.023) and greater lymph node metastasis (p = 0.048), lymphatic permeation (p = 0.046), and vascular invasion (p = 0.010). Compared with patients with non-invasive tumors, patients with invasive tumors had a tumor size >2.0 cm (p = 0.001), serum CEA >5.0 mg/dL (p < 0.001), high urinary DiAcSpm (p = 0.002), and a tumor disappearance rate (TDR) <0.75 (p < 0.001). Multivariate analysis revealed that a tumor size < 2.0 cm (RR = 2.901, 95% CI; 1.372-6.136, p = 0.005), high urinary DiAcSpm (RR = 3.374, 95% CI; 1.547-7.361, p = 0.002), and TDR < 0.75 (RR = 4.673, 95% CI; 2.178-10.027, p < 0.001) were independent predictors for invasive tumors.
  
  
  CONCLUSIONS
  We successfully showed that there was a significant correlation between urinary DiAcSpm levels and pathological tumor invasiveness in patients with clinical stage IA NSCLC. Further research would elucidate the clinical usefulness of DiAcSpm levels as a predictor of tumor invasiveness.
authors.affiliation: Department of Thoracic Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22 Hon-komagome, Bunkyo-ku, Tokyo, Japan. yusuketakahashigts@gmail.com.|Department of General Thoracic Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, Japan. yusuketakahashigts@gmail.com.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Department of Thoracic Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22 Hon-komagome, Bunkyo-ku, Tokyo, Japan. hirohori@cick.jp.
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Horio
authors.affiliation: Department of Thoracic Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22 Hon-komagome, Bunkyo-ku, Tokyo, Japan. sakaguchi-kouji@pref-nagano-hosp.jp.|Department of Thoracic Surgery, Nagano Prefectural Suzaka Hospital, 1332 Oaza-suzaka, Suzaka, Nagano, Japan. sakaguchi-kouji@pref-nagano-hosp.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Sakaguchi
authors.affiliation: Center for Medical Research Cooperation, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kami-kitazawa, Setagaya-ku, Tokyo, Japan. hiramatsu-kk@igakuken.or.jp.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hiramatsu
authors.affiliation: Center for Medical Research Cooperation, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kami-kitazawa, Setagaya-ku, Tokyo, Japan. kawakita-ms@igakuken.or.jp.
authors.forename: Masao
authors.initials: M
authors.lastname: Kawakita
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology* / Q000652:urine; D003404:Creatinine / Q000652:urine; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology* / Q000652:urine; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D013096:Spermine / Q000031:analogs & derivatives* / Q000652:urine
chemical_list: D014408:Biomarkers, Tumor; D013096:Spermine; C029453:N',N''-diacetylspermine; D003404:Creatinine