title: Expression of Na+-K+-2Cl- cotransporter isoform 1 (NKCC1) predicts poor prognosis in lung adenocarcinoma and EGFR-mutated adenocarcinoma patients.
abstract: BACKGROUND
  Sodium-potassium-chloride cotransporter isoform 1 (NKCC1) is an active ions cotransporter and modulates cellular volume and migration. NKCC1 blockers can inhibit cancer cell growth.
  
  
  OBJECTIVE
  We aimed to elucidate the expression and prognostic significance of NKCC1 in non-small cell lung cancer (NSCLC).
  
  
  METHODS
  We retrospectively analyzed 788 NSCLC patients with either adenocarcinoma (n = 503) or squamous cell carcinoma (n = 285) by immunohistochemistry to correlate NKCC1 expression with clinicopathologic and survival outcomes.
  
  
  RESULTS
  In adenocarcinoma, high NKCC1 expression was associated with larger tumor size (P = 0.013), vascular invasion (P < 0.001), lymphatic invasion (P < 0.001), perineural invasion (P = 0.019) and advanced pathologic stage (P < 0.001), but there are no significant correlations between NKCC1 expression and clinicopathological parameters in squamous cell carcinoma. Patients with high NKCC1 expression had significantly shorter disease-free survival (DFS;P < 0.001) and shorter overall survival (OS;P < 0.001) than those with low NKCC1 expression in adenocarcinoma. In squamous cell carcinoma, NKCC1 expression was not associated with prognosis. Multivariate analysis revealed that high NKCC1 expression was an independent prognostic factor for DFS in lung adenocarcinomas (HR, 1.709; 95% CI 1.029-2.130;P = 0.033) and for OS inEGFR-mutated adenocarcinoma patients (HR, 3.165; 95% CI 1.424-7.035;P = 0.005).
  
  
  CONCLUSIONS
  NKCC1 high expression predicted a bad clinical outcome for lung adenocarcinoma patients andEGFR-mutated subgroup. Therefore, NKCC1 may play a role in lung adenocarcinoma and novel therapeutic tactics could be developed by targeting NKCC1 protein.
authors.affiliation: From the Department of Pathology, Second Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Ping-Li
authors.initials: PL
authors.lastname: Sun
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Jongno-Gu, Seoul, Republic of Korea.
authors.forename: Hyojin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Jongno-Gu, Seoul, Republic of Korea.
authors.forename: Eunhyang
authors.initials: E
authors.lastname: Park
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
authors.forename: Sanghoon
authors.initials: S
authors.lastname: Jheon
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
authors.forename: Kwhanmien
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
authors.forename: Choon-Taek
authors.initials: CT
authors.lastname: Lee
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea chungjh@snu.ac.kr.
authors.forename: Jin-Haeng
authors.initials: JH
authors.lastname: Chung
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D016016:Proportional Hazards Models; D056910:Republic of Korea; D012189:Retrospective Studies; D064506:Solute Carrier Family 12, Member 2 / Q000235:genetics*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C578877:SLC12A2 protein, human; D064506:Solute Carrier Family 12, Member 2; C512478:EGFR protein, human; D066246:ErbB Receptors