title: High PHLPP expression is associated with better prognosis in patients with resected lung adenocarcinoma.
abstract: BACKGROUND
  PH domain Leucine-rich-repeats protein phosphatase (PHLPP) is a novel family of Ser/Thr protein dephosphatases that play a critical role in maintaining the balance in cell signaling. PHLPP negatively regulates PI3K/Akt and RAF/RAS/' signaling activation, which is crucial in development, growth, and proliferation of lung cancer. The aim of this study was to investigate the association of PHLPP expression with biological behavior and prognosis of lung adenocarcinoma.
  
  
  METHODS
  One hundred and fifty eight patients with pathologically documented stage I, II or IIIA lung adenocarcinoma were recruited in this study. Expression of PHLPP, p-AKT and p-ERK were evaluated by immunohistochemistry (IHC) in paraffin-embedded resected specimens. The correlation of their expression, which was dichotomized to low expression (a score of 0, 1) versus high expression (a score of 2, 3), with the clinicopathological parameters and prognosis of the patients also analyzed.
  
  
  RESULTS
  High PHLPP expression rate in lung adenocarcinoma was 23.4 %. PHLPP expression level was significantly associated with tumor differentiation (p = 0.025) and tumor stage (p = 0.024). Patients with high expression of PHLPP showed significantly longer average survival time and higher 3 years survival rate than those with low expression of PHLPP (45 months versus 38 months, 85.8 % versus 73.5 % respectively) (Log rank test x(2) = 7.086, p =0.008). A significant inverse correlation was observed between PHLPP expression and p-AKT (r = -0.523, p = 0.000) or p-ERK (r = -0.530, p = 0.000).
  
  
  CONCLUSIONS
  Our results suggest that high levels of PHLPP might reflect a less aggressive lung adenocarcinoma phenotype and predict better survival in patients with lung adenocarcinoma. PHLPP can be a potential prognostic marker to screen patients for favorable prognoses.
authors.affiliation: Laboratory of Cellular and Molecular Radiation Oncology, Taizhou Hospital, Wenzhou Medical University, Zhejiang Province, 317000, China. lvdq@enzemed.com.|Department of Pulmonary Medicine, Taizhou Hospital, Wenzhou Medical University, Zhejiang Province, 317000, China. lvdq@enzemed.com.
authors.forename: Dongqing
authors.initials: D
authors.lastname: Lv
authors.affiliation: Laboratory of Cellular and Molecular Radiation Oncology, Taizhou Hospital, Wenzhou Medical University, Zhejiang Province, 317000, China. yhh93181@hotmail.com.|Department of Radiation Oncology, Taizhou Hospital, Wenzhou Medical University, Zhejiang Province, 317000, China. yhh93181@hotmail.com.
authors.forename: Haihua
authors.initials: H
authors.lastname: Yang
authors.affiliation: Laboratory of Cellular and Molecular Radiation Oncology, Taizhou Hospital, Wenzhou Medical University, Zhejiang Province, 317000, China. w.w11520@hotmail.com.|Department of Radiation Oncology, Taizhou Hospital, Wenzhou Medical University, Zhejiang Province, 317000, China. w.w11520@hotmail.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Laboratory of Cellular and Molecular Radiation Oncology, Taizhou Hospital, Wenzhou Medical University, Zhejiang Province, 317000, China. xieyy@enzemed.com.|Department of Radiation Oncology, Taizhou Hospital, Wenzhou Medical University, Zhejiang Province, 317000, China. xieyy@enzemed.com.
authors.forename: Youyou
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Laboratory of Cellular and Molecular Radiation Oncology, Taizhou Hospital, Wenzhou Medical University, Zhejiang Province, 317000, China. Huw@enzemed.com.|Department of Radiation Oncology, Taizhou Hospital, Wenzhou Medical University, Zhejiang Province, 317000, China. Huw@enzemed.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Thoracic Surgery, Taizhou Hospital, Wenzhou Medical University, Zhejiang Province, 317000, China. ymh@enzemed.com.
authors.forename: Minhua
authors.initials: M
authors.lastname: Ye
authors.affiliation: Enze Medical Research Center, Taizhou Hospital, Wenzhou Medical University, Zhejiang Province, 317000, China. chenxf@enzemed.com.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C400601:PHLPP1 protein, human; D010749:Phosphoprotein Phosphatases