ROR1 and ROR2 expression in pancreatic cancer

Abstract Background The Wnt receptors ROR1 and ROR2 are generating increased interest as cancer therapeutic targets but remain understudied in pancreatic ductal adenocarcinoma (PDAC). Compared to canonical Wnt/ β-catenin signalling, the role of noncanonical Wnt signalling in PDAC remains largely unk...

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Autores principales: Dongli Liu, George Sharbeen, Phoebe Phillips, Australian Pancreatic Cancer Genome Initiative, Caroline E. Ford
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Lenguaje:EN
Publicado: BMC 2021
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Acceso en línea:https://doaj.org/article/77c1d36dfb864511964d2a94105709b4
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spelling oai:doaj.org-article:77c1d36dfb864511964d2a94105709b42021-11-14T12:30:17ZROR1 and ROR2 expression in pancreatic cancer10.1186/s12885-021-08952-91471-2407https://doaj.org/article/77c1d36dfb864511964d2a94105709b42021-11-01T00:00:00Zhttps://doi.org/10.1186/s12885-021-08952-9https://doaj.org/toc/1471-2407Abstract Background The Wnt receptors ROR1 and ROR2 are generating increased interest as cancer therapeutic targets but remain understudied in pancreatic ductal adenocarcinoma (PDAC). Compared to canonical Wnt/ β-catenin signalling, the role of noncanonical Wnt signalling in PDAC remains largely unknown. Only one study has investigated the prognostic significance of the noncanonical Wnt signalling receptor, ROR2 in PDAC. No studies have investigated the prognostic role of ROR1 in PDAC. Methods Here, we performed analysis of ROR1 and ROR2 mRNA expression in three publicly available datasets ICGC-PACA-AU (n = 81), TCGA-PAAD (n = 150) and CPTAC-PDAC (n = 137). ROR1 and ROR2 protein expression from the CPTAC-PDAC discovery cohort were also analysed. Immunohistochemistry (IHC) using the validated anti ROR1 monoclonal antibody (4A5) was performed on the Australian Pancreatic Cancer Genome Initiative (APGI) cohort of PDAC samples (n = 152). Association between ROR1 cytoplasmic staining intensity and clinicopathological parameters including stage, grade and overall survival (OS) was investigated. Results High ROR1 mRNA expression levels correlated with a favourable OS outcome in all of the ICGC-PACA-AU, TCGA-PAAD and CPTAC-PDAC cohorts. ROR1 protein expression was not associated with stage, grade or OS in the APGI cohort. Conclusion ROR1 and ROR2 have potential as prognostic markers when measured at the mRNA level in PDAC. Our IHC cohort did not support ROR1 protein expression in predicting OS, and highlighted the discrepancy of prognostic biomarkers when measured by MS, IHC and RNAseq.Dongli LiuGeorge SharbeenPhoebe PhillipsAustralian Pancreatic Cancer Genome InitiativeCaroline E. FordBMCarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBMC Cancer, Vol 21, Iss 1, Pp 1-11 (2021)
institution DOAJ
collection DOAJ
language EN
topic Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Dongli Liu
George Sharbeen
Phoebe Phillips
Australian Pancreatic Cancer Genome Initiative
Caroline E. Ford
ROR1 and ROR2 expression in pancreatic cancer
description Abstract Background The Wnt receptors ROR1 and ROR2 are generating increased interest as cancer therapeutic targets but remain understudied in pancreatic ductal adenocarcinoma (PDAC). Compared to canonical Wnt/ β-catenin signalling, the role of noncanonical Wnt signalling in PDAC remains largely unknown. Only one study has investigated the prognostic significance of the noncanonical Wnt signalling receptor, ROR2 in PDAC. No studies have investigated the prognostic role of ROR1 in PDAC. Methods Here, we performed analysis of ROR1 and ROR2 mRNA expression in three publicly available datasets ICGC-PACA-AU (n = 81), TCGA-PAAD (n = 150) and CPTAC-PDAC (n = 137). ROR1 and ROR2 protein expression from the CPTAC-PDAC discovery cohort were also analysed. Immunohistochemistry (IHC) using the validated anti ROR1 monoclonal antibody (4A5) was performed on the Australian Pancreatic Cancer Genome Initiative (APGI) cohort of PDAC samples (n = 152). Association between ROR1 cytoplasmic staining intensity and clinicopathological parameters including stage, grade and overall survival (OS) was investigated. Results High ROR1 mRNA expression levels correlated with a favourable OS outcome in all of the ICGC-PACA-AU, TCGA-PAAD and CPTAC-PDAC cohorts. ROR1 protein expression was not associated with stage, grade or OS in the APGI cohort. Conclusion ROR1 and ROR2 have potential as prognostic markers when measured at the mRNA level in PDAC. Our IHC cohort did not support ROR1 protein expression in predicting OS, and highlighted the discrepancy of prognostic biomarkers when measured by MS, IHC and RNAseq.
format article
author Dongli Liu
George Sharbeen
Phoebe Phillips
Australian Pancreatic Cancer Genome Initiative
Caroline E. Ford
author_facet Dongli Liu
George Sharbeen
Phoebe Phillips
Australian Pancreatic Cancer Genome Initiative
Caroline E. Ford
author_sort Dongli Liu
title ROR1 and ROR2 expression in pancreatic cancer
title_short ROR1 and ROR2 expression in pancreatic cancer
title_full ROR1 and ROR2 expression in pancreatic cancer
title_fullStr ROR1 and ROR2 expression in pancreatic cancer
title_full_unstemmed ROR1 and ROR2 expression in pancreatic cancer
title_sort ror1 and ror2 expression in pancreatic cancer
publisher BMC
publishDate 2021
url https://doaj.org/article/77c1d36dfb864511964d2a94105709b4
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AT georgesharbeen ror1andror2expressioninpancreaticcancer
AT phoebephillips ror1andror2expressioninpancreaticcancer
AT australianpancreaticcancergenomeinitiative ror1andror2expressioninpancreaticcancer
AT carolineeford ror1andror2expressioninpancreaticcancer
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