title: Expression of GRK2 and IGF1R in hepatocellular carcinoma: clinicopathological and prognostic significance.
abstract: OBJECTIVE
  It has been shown that G-protein-coupled receptor kinase 2 (GRK2) negatively regulates the insulin-like growth factor 1 receptor (IGF1R) signalling pathway in hepatocellular carcinoma (HCC). The aim of this study was to evaluate the clinicopathological and prognostic significance of GRK2 and IGF1R in HCC.
  
  
  METHODS
  Expression of GRK2 and IGF1R was first detected by tissue microarray-based immunohistochemistry in 156 patients with HCC. Staining results, termed the H-score, were then correlated with clinicopathological variables and patient survival. Finally, the prognostic value of GRK2 and IGF1R was validated in the publically available TCGA (The Cancer Genome Atlas) RNA-sequencing database.
  
  
  RESULTS
  The H-score of GRK2 staining (which was significantly lower in tumour than non-tumour tissue) was negatively associated with that of IGF1R with a reverse trend. No clinicopathological significance of the proteins was found except for a relationship between tumoral IGF1R expression and tumour-node-metastasis stage. In univariate analysis, high IGF1R expression predicted poor overall and disease-free survival, whereas GRK2 was not prognostic. In multivariate analysis, IGF1R was significant for overall survival. Furthermore, IGF1R was also of prognostic value in the TCGA database.
  
  
  CONCLUSIONS
  Our data indicate that GRK2 and IGF1R show a negative correlation in HCC. IGF1R could be a potential marker of poor prognosis for this malignancy.
authors.affiliation: International Medical Services, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China.
authors.forename: Song-Bai
authors.initials: SB
authors.lastname: Lin
authors.affiliation: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Liang
authors.affiliation: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China.
authors.forename: Wei-Xun
authors.initials: WX
authors.lastname: Zhou
authors.affiliation: Clinical Research Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000556:secondary / Q000601:surgery; D016009:Chi-Square Distribution; D030541:Databases, Genetic; D018572:Disease-Free Survival; D005260:Female; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000032:analysis* / Q000235:genetics; D012307:Risk Factors; D017423:Sequence Analysis, RNA; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C000597236:IGF1R protein, human; D017451:Receptors, Somatomedin; D017526:Receptor, IGF Type 1; C496567:GRK2 protein, human; D054769:G-Protein-Coupled Receptor Kinase 2
keywords: CANCER RESEARCH; HISTOPATHOLOGY; LIVER CANCER; PROTEINS; SURGICAL PATHOLOGY