title: CD147-CD98hc complex contributes to poor prognosis of non-small cell lung cancer patients through promoting cell proliferation via the PI3K/Akt signaling pathway.
abstract: BACKGROUND
  It has been reported that CD147 and CD98 heavy chain (CD98hc) form a complex on the cell plasma membrane of several cancers; however, whether this complex exists in non-small cell lung cancer (NSCLC) cells and affects the prognosis of patients remains to be elucidated.
  
  
  METHODS
  The expression of CD147 and CD98hc was assessed in tissue samples from 241 NSCLC patients and NSCLC cell lines. The correlation between CD147 and CD98hc expression and their association with the prognosis of NSCLC patients were analyzed. We also evaluated the impact of CD147 and CD98hc on the growth of NSCLC cells as well as Akt phosphorylation.
  
  
  RESULTS
  Both CD147 and CD98hc were significantly upregulated in NSCLC cells, and their expression levels were significantly correlated (p < 0.001). Immunoflurenece staining and co-immunoprecipitation demonstrated that CD147 and CD98hc could form a complex on NSCLC cells. Compared with NSCLC patients with CD147-/CD98hc-, those with CD147+/CD98hc+ exhibited a significantly poor overall survival (OS) with a hazard ratio (HR) of 1.92 (p = 0.010), and a significantly increased risk of recurrence with a HR of 1.97 (p = 0.004). Also, we demonstrated that the proliferation of lung cancer cell lines was significantly affected by knockdown and force-expression of the CD147-CD98hc complex. Western blot analysis indicated that the phosphorylation of Akt in NSCLC cells was significantly affected by knockdown and overexpression of either or both CD147 and CD98hc.
  
  
  CONCLUSIONS
  Our findings indicate that the CD147-CD98hc complex significantly contributes to poor prognosis of NSCLC patients through promoting cell proliferation via the PI3K/Akt pathway.
authors.affiliation: State Key Laboratory of Cancer Biology, Cell Engineering Research Center & Department of Cell Biology, The Fourth Military Medical University, Xi'an, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Fei
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.forename: Deyang
authors.initials: D
authors.lastname: Li
authors.forename: Zhipei
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xu
authors.initials: X
authors.lastname: Guo
authors.forename: Hushan
authors.initials: H
authors.lastname: Yang
authors.forename: Zhinan
authors.initials: Z
authors.lastname: Chen
authors.forename: Jinliang
authors.initials: J
authors.lastname: Xing
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D051926:Basigin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D005260:Female; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D027282:Fusion Regulatory Protein 1, Heavy Chain; D027261:Fusion Regulatory Protein-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D015996:Survival Rate
chemical_list: C497886:BSG protein, human; D027282:Fusion Regulatory Protein 1, Heavy Chain; D027261:Fusion Regulatory Protein-1; D034741:RNA, Small Interfering; C545989:SLC3A2 protein, human; D051926:Basigin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt