Significant association and synergistic adverse prognostic effect of podocalyxin-like protein and epidermal growth factor receptor expression in colorectal cancer

Journal of Translational Medicine

Research

Eugenia Kuteeva¹  Magnus Sundström²  Helgi Birgisson³  Sakarias Wangefjord⁴  Jakob Eberhard⁴  Anna H. Larsson⁴  Sophie Lehn⁴  Karin Jirström⁴  Björn Nodin⁴  Emelie Karnevi⁴  Mathias Uhlén⁵ 

[1] Atlas Antibodies AB, AlbaNova University Center, Stockholm, Sweden;Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden;Department of Surgical Sciences, Colorectal Surgery, Uppsala University, Uppsala, Sweden;Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden;Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden;

关键词: Podocalyxin-like;    EGFR;    BRAF;    Colorectal cancer;    Prognosis;   

DOI  :  10.1186/s12967-016-0882-0

 received in 2015-10-07, accepted in 2016-04-28,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundPodocalyxin-like 1 (PODXL) is an anti-adhesive transmembrane protein that has been demonstrated to be an independent factor of poor prognosis in colorectal cancer (CRC). The gene encoding PODXL is located to chromosome 7, which also harbours the gene for the epidermal growth factor receptor (EGFR). The aim of this study was to examine the associations between PODXL and EGFR expression in CRC in vitro and in vivo.MethodsEGFR expression was analysed in tumours from three independent patient cohorts; cohort 1 (n = 533), cohort 2 (n = 259) and cohort 3 (n = 310), previously analysed for immunohistochemical PODXL expression and KRAS and BRAF mutations (cohort 1 and 3). Levels of EGFR and PODXL were determined by western blot in six different CRC cell lines.ResultsHigh expression of PODXL was significantly associated with high EGFR expression (p < 0.001) in all three cohorts, and with BRAF mutation (p < 0.001) in cohort 1 and 3. High EGFR expression correlated with BRAF mutation (p < 0.001) in cohort 1. High EGFR expression was associated with adverse clinicopathological factors and independently predicted a reduced 5-year overall survival (OS) in cohort 1 (HR 1.77; 95 % CI 1.27–2.46), cohort 2 (HR 1.58; 95 % CI 1.05–2.38) and cohort 3 (HR 1.83; 95 % CI 1.19–2.81). The highest risk of death within 5 years was observed in patients with tumours displaying high expression of both EGFR and PODXL in cohort 1 and 3 (HR 1.97; 95 % CI 1.18–3.28 and HR 3.56; 95 % CI 1.75–7.22, respectively). Western blot analysis showed a uniform expression of PODXL and EGFR in all six examined CRC cell lines.ConclusionsThe results from this study demonstrate that high expression of EGFR is an independent factor of poor prognosis in CRC. Moreover, strong links have been uncovered between expression of the recently proposed biomarker candidate PODXL with EGFR expression in CRC in vivo and in vitro, and with BRAF mutation in vivo. High expression of both PODXL and EGFR may also have a synergistic adverse effect on survival. These findings suggest a potential functional link in CRC between PODXL, EGFR and BRAF, all originating from chromosome 7, which may be highly relevant in the clinical setting and therefore merit future in-depth study.

【 授权许可】

CC BY   
© The Author(s) 2016