title: Combining clinicopathological predictors and molecular biomarkers in the oncogenic K-RAS/Ki67/HIF-1α pathway to predict survival in resectable pancreatic cancer.
abstract: BACKGROUND
  The dismal prognosis of patients diagnosed with pancreatic cancer points to our limited arsenal of effective anticancer therapies. Oncogenic K-RAS hyperactivation is virtually universal in pancreatic cancer, that confers drug resistance, drives aggressive tumorigenesis and rapid metastasis. Pancreatic tumours are often marked by hypovascularity, increased hypoxia and ineffective drug delivery. Thus, biomarker discovery and developing innovative means of countervailing oncogenic K-RAS activation are urgently needed.
  
  
  METHODS
  Tumour specimens from 147 pancreatic cancer patients were analysed by immunohistochemical (IHC) staining and tissue microarray (TMA). Statistical correlations between selected biomarkers and clinicopathological predictors were examined to predict survival.
  
  
  RESULTS
  We find that heightened hypoxia response predicts poor clinical outcome in resectable pancreatic cancer. SIAH is a tumour-specific biomarker. The combination of five biomarkers (EGFR, phospho-ERK, SIAH, Ki67 and HIF-1α) and four clinicopathological predictors (tumour size, pathological grade, margin and lymph node status) predict patient survival post surgery in pancreatic cancer.
  
  
  CONCLUSIONS
  Combining five biomarkers in the K-RAS/Ki67/HIF-1α pathways with four clinicopathological predictors may assist to better predict survival in resectable pancreatic cancer.
authors.affiliation: Department of Health Sciences Research, Mayo Clinic Cancer Center, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: R
authors.initials: R
authors.lastname: Qin
authors.affiliation: Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic Cancer Center, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Smyrk
authors.affiliation: Department of Surgery, Mayo Clinic Cancer Center, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: N R
authors.initials: NR
authors.lastname: Reed
authors.affiliation: 1] Department of Biochemistry and Molecular Biology, Mayo Clinic Cancer Center, Mayo Clinic, Rochester, MN 55905, USA [2] Upper Iowa University, Fayette, IA 52142, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Schmidt
authors.affiliation: Department of Surgery, Mayo Clinic Cancer Center, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: T
authors.initials: T
authors.lastname: Schnelldorfer
authors.affiliation: 1] Department of Medicine, Mayo Clinic Cancer Center, Mayo Clinic, Rochester, MN 55905, USA [2] Department of Oncology, Mayo Clinic Cancer Center, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: S T
authors.initials: ST
authors.lastname: Chari
authors.affiliation: Department of Health Sciences Research, Mayo Clinic Cancer Center, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: G M
authors.initials: GM
authors.lastname: Petersen
authors.affiliation: 1] Department of Surgery, Mayo Clinic Cancer Center, Mayo Clinic, Rochester, MN 55905, USA [2] Department of Biochemistry and Molecular Biology, Mayo Clinic Cancer Center, Mayo Clinic, Rochester, MN 55905, USA [3] Department of Microbiology and Molecular Cell Biology, Leroy T. Canoles Jr. Cancer Research Center, Eastern Virginia Medical School, Norfolk, VA 23507, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Tang
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis* / Q000378:metabolism; D019394:Ki-67 Antigen / Q000032:analysis* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D015398:Signal Transduction; D016019:Survival Analysis; D046888:Tissue Array Analysis; D018631:ras Proteins / Q000032:analysis* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C117307:KRAS protein, human; D019394:Ki-67 Antigen; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins