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

Larsson AH, Lehn S, Wangefjord S, Karnevi E, Kuteeva E, Sundström M, Nodin B, Uhlén M, Eberhard J, Birgisson H, Jirström K - J Transl Med (2016)

Bottom Line: EGFR 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.High expression of both PODXL and EGFR may also have a synergistic adverse effect on survival.

View Article: PubMed Central - PubMed

Affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden. anna_h.larsson@med.lu.se.

ABSTRACT

Background: Podocalyxin-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.

Methods: EGFR 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.

Results: High 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.

Conclusions: The 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.

No MeSH data available.


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Western blot and immunocytochemical analysis of EGFR and PODXL in CRC cells. a Western blot and b immunocytochemical analysis of PODXL and EGFR protein levels in six different CRC cell lines; Caco-2, SW480, SW620, HCT-116, RKO and HT-29
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Fig3: Western blot and immunocytochemical analysis of EGFR and PODXL in CRC cells. a Western blot and b immunocytochemical analysis of PODXL and EGFR protein levels in six different CRC cell lines; Caco-2, SW480, SW620, HCT-116, RKO and HT-29

Mentions: As shown in Fig. 3, western blot analysis demonstrated that all cell lines with expression of PODXL also expressed EGFR, whereas the cell lines without PODXL expression did not. In cell lines derived from the same patient, EGFR and PODXL were expressed in the primary tumour cell line (SW480), but not in the metastatic derivative (SW620).Fig. 3


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

Larsson AH, Lehn S, Wangefjord S, Karnevi E, Kuteeva E, Sundström M, Nodin B, Uhlén M, Eberhard J, Birgisson H, Jirström K - J Transl Med (2016)

Western blot and immunocytochemical analysis of EGFR and PODXL in CRC cells. a Western blot and b immunocytochemical analysis of PODXL and EGFR protein levels in six different CRC cell lines; Caco-2, SW480, SW620, HCT-116, RKO and HT-29
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4862047&req=5

Fig3: Western blot and immunocytochemical analysis of EGFR and PODXL in CRC cells. a Western blot and b immunocytochemical analysis of PODXL and EGFR protein levels in six different CRC cell lines; Caco-2, SW480, SW620, HCT-116, RKO and HT-29
Mentions: As shown in Fig. 3, western blot analysis demonstrated that all cell lines with expression of PODXL also expressed EGFR, whereas the cell lines without PODXL expression did not. In cell lines derived from the same patient, EGFR and PODXL were expressed in the primary tumour cell line (SW480), but not in the metastatic derivative (SW620).Fig. 3

Bottom Line: EGFR 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.High expression of both PODXL and EGFR may also have a synergistic adverse effect on survival.

View Article: PubMed Central - PubMed

Affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden. anna_h.larsson@med.lu.se.

ABSTRACT

Background: Podocalyxin-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.

Methods: EGFR 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.

Results: High 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.

Conclusions: The 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.

No MeSH data available.


Related in: MedlinePlus