title: Aberrant large tumor suppressor 2 (LATS2) gene expression correlates with EGFR mutation and survival in lung adenocarcinomas.
abstract: BACKGROUND
  Large tumor suppressor 2 (LATS2) gene is a putative tumor suppressor gene with potential roles in regulation of cell proliferation and apoptosis in lung cancer. The aim of this study is to explore the association of aberrant LATS2 expression with EGFR mutation and survival in lung adenocarcinoma (AD), and the effects of LATS2 silencing in both lung AD cell lines.
  
  
  METHODS
  LATS2 mRNA and protein expression in resected lung AD were correlated with demographic characteristics, EGFR mutation and survival. LATS2-specific siRNA was transfected into four EGFR wild-type (WT) and three EGFR mutant AD cell lines and the changes in LATS2 expression and relevant signaling molecules before and after LATS2 knockdown were assayed.
  
  
  RESULTS
  Fifty resected lung AD were included (M:F=23:27, smokers:non-smokers=19:31, EGFR mutant:wild-type=21:29) with LATS2 mRNA levels showed no significant difference between gender, age, smoking and pathological stages while LATS2 immunohistochemical staining on an independent set of 79 lung AD showed similar trend. LATS2 mRNA level was found to be a significant independent predictor for survival status (disease-free survival RR=0.217; p=0.003; Overall survival RR=0.238; p=0.036). siRNA-mediated suppression of LATS2 expression resulted in augmentation of ERK phosphorylation in EGFR wild-type AD cell lines with high basal LATS2 expression, discriminatory modulation of Akt signaling between EGFR wild-type and mutant cells, and induction of p53 accumulation in AD cell lines with low baseline p53 levels.
  
  
  CONCLUSIONS
  LATS2 expression level is predictive of survival in patients with resected lung AD. LATS2 may modulate and contribute to tumor growth via different signaling pathways in EGFR mutant and wild-type tumors.
authors: Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong.
authors: Susan Y
authors: SY
authors: Luo
authors: Department of Cardiothoracic Surgery, Queen Mary Hospital, University of Hong Kong, Hong Kong.
authors: Ko-Yung
authors: KY
authors: Sit
authors: Department of Cardiothoracic Surgery, Queen Mary Hospital, University of Hong Kong, Hong Kong.
authors: Alan D L
authors: AD
authors: Sihoe
authors: Department of Cardiothoracic Surgery, Queen Mary Hospital, University of Hong Kong, Hong Kong.
authors: Wai-Sing
authors: WS
authors: Suen
authors: Department of Cardiothoracic Surgery, Queen Mary Hospital, University of Hong Kong, Hong Kong.
authors: Wing-Kuk
authors: WK
authors: Au
authors: Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, USA.
authors: Ximing
authors: X
authors: Tang
authors: Department of Pathology, Hong Kong Sanatorium and Hospital, Hong Kong.
authors: Edmond S K
authors: ES
authors: Ma
authors: Department of Pathology, Hong Kong Sanatorium and Hospital, Hong Kong.
authors: Wai-Kong
authors: WK
authors: Chan
authors: Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, USA.
authors: Ignacio I
authors: II
authors: Wistuba
authors: Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center at Dallas, TX, USA.
authors: John D
authors: JD
authors: Minna
authors: Department of Anatomy, Queen Mary Hospital, University of Hong Kong, Hong Kong.
authors: George S W
authors: GS
authors: Tsao
authors: Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong. Electronic address: dcllam@hku.hk.
authors: David C L
authors: DC
authors: Lam
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000601:surgery; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000601:surgery; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C406449:LATS2 protein, human; D066246:ErbB Receptors; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: EGFR signaling; Gene expression; Gene silencing; Large tumor suppressor 2 gene; Lung cancer