title: Differential expression of IQGAP1/2 in Hepatocellular carcinoma and its relationship with clinical outcomes.
abstract: OBJECTIVE
  To investigate IQGAP1 and IQGAP2 expression in hepatocellular carcinoma (HCC) and itsassociation with HCC clinicopathological characteristics and survival outcomes.
  
  
  METHODS
  IQGAP1 and IQGAP2 mRNA and protein were measured in HCC tissues, para-tumor tissues and normal tissues by RT-PCR and Western blotting. We further examined 150 HCC samples with adjacent para-tumor tissues and 11 normal specimens by immunohistochemistry to evaluate the correlation of IQGAP1 and IQGAP2 with clinicopathological features and prognosis.
  
  
  RESULTS
  IQGAP1 mRNA and protein were up-regulated while IQGAP2 mRNA and protein were down-regulated in human HCC tissues compared with para-tumor and normal liver tissues (p<0.05). IQGAP1 expression was higher in primary HCC (122/150, 81.3%) than matched adjacent tissues (30/150, 20%, p<0.001), whereas IQGAP2 was lower (31/150, 20.7% as compared to 112/150, 74.7%, P<0.001). Positive IQGAP1 expression correlated with larger tumor size (p=0.002), advanced TNM stage (p=0.002) and tumor differentiation (III and IV, p=0.034). Negative IQGAP2 expression was significantly associated with larger tumor size (p=0.009), multicentric tumor occurrence (p=0.01), advanced TNM stage (0.009) and tumor differentiation (III and IV, p=0.020). Survival analysis revealed that patients with either IQGAP1+ or IQGAP2- tumors had significantly reduced disease-free survival (p<0.001 and 0.006 respectively) and overall survival (p<0.001 for both). Multivariate analysis showed that IQGAP1/2 switch was an independent prognosis factor for disease-free survival (HR=2.824) and overall survival (HR=2.189).
  
  
  CONCLUSIONS
  Positive IQGAP1 and negative IQGAP2 expression were closely correlated with tumor progression and could be used as adjunctive biomarkers to improve prognostication for HCC patients.
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China E-mail : lixinyingcn@126.com.
authors.forename: Fa-Da
authors.initials: FD
authors.lastname: Xia
authors.forename: Zhuo-Lu
authors.initials: ZL
authors.lastname: Wang
authors.forename: Hong-Xi
authors.initials: HX
authors.lastname: Chen
authors.forename: Yun
authors.initials: Y
authors.lastname: Huang
authors.forename: Jin-Dong
authors.initials: JD
authors.lastname: Li
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Wang
authors.forename: Xin-Ying
authors.initials: XY
authors.lastname: Li
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C101203:IQ motif containing GTPase activating protein 1; C101002:IQGAP2 protein, human; D012333:RNA, Messenger; D020703:ras GTPase-Activating Proteins