title: Validation of podocalyxin-like protein as a biomarker of poor prognosis in colorectal cancer.
abstract: BACKGROUND
  Podocalyxin-like 1 (PODXL) is a cell-adhesion glycoprotein and stem cell marker that has been associated with an aggressive tumour phenotype and adverse outcome in several cancer types. We recently demonstrated that overexpression of PODXL is an independent factor of poor prognosis in colorectal cancer (CRC). The aim of this study was to validate these results in two additional independent patient cohorts and to examine the correlation between PODXL mRNA and protein levels in a subset of tumours.
  
  
  METHODS
  PODXL protein expression was analyzed by immunohistochemistry in tissue microarrays with tumour samples from a consecutive, retrospective cohort of 270 CRC patients (cohort 1) and a prospective cohort of 337 CRC patients (cohort 2). The expression of PODXL mRNA was measured by real-time quantitative PCR in a subgroup of 62 patients from cohort 2. Spearman's Rho and Chi-Square tests were used for analysis of correlations between PODXL expression and clinicopathological parameters. Kaplan Meier analysis and Cox proportional hazards modelling were applied to assess the relationship between PODXL expression and time to recurrence (TTR), disease free survival (DFS) and overall survival (OS).
  
  
  RESULTS
  High PODXL protein expression was significantly associated with unfavourable clinicopathological characteristics in both cohorts. In cohort 1, high PODXL expression was associated with a significantly shorter 5-year OS in both univariable (HR = 2.28; 95% CI 1.43-3.63, p = 0.001) and multivariable analysis (HR = 2.07; 95% CI 1.25-3.43, p = 0.005). In cohort 2, high PODXL expression was associated with a shorter TTR (HR = 2.93; 95% CI 1.26-6.82, p = 0.013) and DFS (HR = 2.44; 95% CI 1.32-4.54, p = 0.005), remaining significant in multivariable analysis, HR = 2.50; 95% CI 1.05-5.96, p = 0.038 for TTR and HR = 2.11; 95% CI 1.13-3.94, p = 0.019 for DFS.No significant correlation could be found between mRNA levels and protein expression of PODXL and there was no association between mRNA levels and clinicopathological parameters or survival.
  
  
  CONCLUSIONS
  Here, we have validated the previously demonstrated association between immunohistochemical expression of PODXL and poor prognosis in CRC in two additional independent patient cohorts. The results further underline the potential utility of PODXL as a biomarker for more precise prognostication and treatment stratification of CRC patients.
authors: Department of Clinical Sciences, Division of Pathology, Lund University, Skåne University Hospital, 221 85, Lund, Sweden. anna_h.larsson@med.lu.se
authors: Anna
authors: A
authors: Larsson
authors: Marie
authors: M
authors: Fridberg
authors: Alexander
authors: A
authors: Gaber
authors: Björn
authors: B
authors: Nodin
authors: Per
authors: P
authors: Levéen
authors: Göran
authors: G
authors: Jönsson
authors: Mathias
authors: M
authors: Uhlén
authors: Helgi
authors: H
authors: Birgisson
authors: Karin
authors: K
authors: Jirström
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D016009:Chi-Square Distribution; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D012795:Sialoglycoproteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C001643:podocalyxin