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Additive clinical impact of epidermal growth factor receptor and podocalyxin-like protein expression in pancreatic and periampullary adenocarcinomas

Heby, Margareta LU ; Karnevi, Emelie LU ; Elebro, Jacob LU ; Nodin, Björn LU ; Eberhard, Jakob LU ; Saukkonen, Kapo ; Hagström, Jaana ; Mustonen, Harri ; Seppänen, Hanna and Haglund, Caj , et al. (2020) In Scientific Reports 10(1).
Abstract

The outcome of periampullary adenocarcinomas remains poor with few treatment options. Podocalyxin-like protein (PODXL) is an anti-adhesive protein, the high expression of which has been shown to confer a poor prognosis in numerous malignancies. A correlation and adverse prognostic synergy between PODXL and the epidermal growth factor receptor (EGFR) has been observed in colorectal cancer. Here, we investigated whether this also applies to periampullary adenocarcinomas. We analyzed the immunohistochemical expression of PODXL and EGFR in tissue microarrays with tumors from two patient cohorts; (Cohort 1, n = 175) and (Cohort 2, n = 189). The effect of TGF-β-induced expression and siRNA-mediated knockdown of PODXL and EGFR, were... (More)

The outcome of periampullary adenocarcinomas remains poor with few treatment options. Podocalyxin-like protein (PODXL) is an anti-adhesive protein, the high expression of which has been shown to confer a poor prognosis in numerous malignancies. A correlation and adverse prognostic synergy between PODXL and the epidermal growth factor receptor (EGFR) has been observed in colorectal cancer. Here, we investigated whether this also applies to periampullary adenocarcinomas. We analyzed the immunohistochemical expression of PODXL and EGFR in tissue microarrays with tumors from two patient cohorts; (Cohort 1, n = 175) and (Cohort 2, n = 189). The effect of TGF-β-induced expression and siRNA-mediated knockdown of PODXL and EGFR, were investigated in pancreatic cancer cells (PANC-1) in vitro. We found a correlation between PODXL and EGFR in these cancers, and a synergistic adverse effect on survival. Furthermore, silencing PODXL in pancreatic cancer cells resulted in the down-regulation of EGFR, but not vice versa. Consequently, these findings suggest a functional link between PODXL and EGFR, and the potential combined utility as biomarkers possibly improving patient stratification. Further studies examining the mechanistic basis underlying these observations may open new avenues of targeted treatment options for subsets of patients affected by these particularly aggressive cancers.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
10
issue
1
article number
10373
publisher
Nature Publishing Group
external identifiers
  • pmid:32587323
  • scopus:85087061625
ISSN
2045-2322
DOI
10.1038/s41598-020-67187-z
language
English
LU publication?
yes
id
bf6ad253-0c4b-49db-ac48-00254e911fa5
date added to LUP
2020-07-07 08:32:04
date last changed
2024-03-04 23:24:56
@article{bf6ad253-0c4b-49db-ac48-00254e911fa5,
  abstract     = {{<p>The outcome of periampullary adenocarcinomas remains poor with few treatment options. Podocalyxin-like protein (PODXL) is an anti-adhesive protein, the high expression of which has been shown to confer a poor prognosis in numerous malignancies. A correlation and adverse prognostic synergy between PODXL and the epidermal growth factor receptor (EGFR) has been observed in colorectal cancer. Here, we investigated whether this also applies to periampullary adenocarcinomas. We analyzed the immunohistochemical expression of PODXL and EGFR in tissue microarrays with tumors from two patient cohorts; (Cohort 1, n = 175) and (Cohort 2, n = 189). The effect of TGF-β-induced expression and siRNA-mediated knockdown of PODXL and EGFR, were investigated in pancreatic cancer cells (PANC-1) in vitro. We found a correlation between PODXL and EGFR in these cancers, and a synergistic adverse effect on survival. Furthermore, silencing PODXL in pancreatic cancer cells resulted in the down-regulation of EGFR, but not vice versa. Consequently, these findings suggest a functional link between PODXL and EGFR, and the potential combined utility as biomarkers possibly improving patient stratification. Further studies examining the mechanistic basis underlying these observations may open new avenues of targeted treatment options for subsets of patients affected by these particularly aggressive cancers.</p>}},
  author       = {{Heby, Margareta and Karnevi, Emelie and Elebro, Jacob and Nodin, Björn and Eberhard, Jakob and Saukkonen, Kapo and Hagström, Jaana and Mustonen, Harri and Seppänen, Hanna and Haglund, Caj and Jirström, Karin and Larsson, Anna H.}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Additive clinical impact of epidermal growth factor receptor and podocalyxin-like protein expression in pancreatic and periampullary adenocarcinomas}},
  url          = {{http://dx.doi.org/10.1038/s41598-020-67187-z}},
  doi          = {{10.1038/s41598-020-67187-z}},
  volume       = {{10}},
  year         = {{2020}},
}