ROR1 and ROR2 expression in pancreatic cancer

Dongli Liu; George Sharbeen; Phoebe Phillips; Caroline E. Ford; Amber L. Johns; Amber L. Gill; Lorraine A. Chantrill; Paul Timpson; Angela Chou; Marina Pajic; Tanya Dwarte; David Herrmann; Claire Vennin; Thomas R. Cox; Brooke Pereira; Shona Ritchie; Daniel A. Reed; Cecilia R. Chambers; Xanthe Metcalf; Max Nobis; Nicola Waddell; John V. Pearson; AnnMarie Patch; Katia Nones; Felicity Newell; Pamela Mukhopadhyay; Venkateswar Addala; Stephen Kazakoff; Oliver Holmes; Conrad Leonard; Scott Wood; Sean M. Grimmond; Oliver Hofmann; Jaswinder S. Samra; Nick Pavlakis; Jennifer Arena; Hilda A. High; Ray Asghari; Neil D. Merrett; Amitabha Das; Peter H. Cosman; Kasim Ismail; Alina Stoita; David Williams; Allan Spigellman; Vincent W. Lam; Duncan McLeod; Judy Kirk; James G. Kench; Peter Grimison; null et al

doi:10.1186/s12885-021-08952-9

ROR1 and ROR2 expression in pancreatic cancer

Dongli Liu, George Sharbeen, Phoebe Phillips, Caroline E. Ford, Amber L. Johns, Amber L. Gill, Lorraine A. Chantrill, Paul Timpson, Angela Chou, Marina Pajic, Tanya Dwarte, David Herrmann, Claire Vennin, Thomas R. Cox, Brooke Pereira, Shona Ritchie, Daniel A. Reed, Cecilia R. Chambers, Xanthe Metcalf, Max NobisNicola Waddell, John V. Pearson, AnnMarie Patch, Katia Nones, Felicity Newell, Pamela Mukhopadhyay, Venkateswar Addala, Stephen Kazakoff, Oliver Holmes, Conrad Leonard, Scott Wood, Sean M. Grimmond, Oliver Hofmann, Jaswinder S. Samra, Nick Pavlakis, Jennifer Arena, Hilda A. High, Ray Asghari, Neil D. Merrett, Amitabha Das, Peter H. Cosman, Kasim Ismail, Alina Stoita, David Williams, Allan Spigellman, Vincent W. Lam, Duncan McLeod, Judy Kirk, James G. Kench, Peter Grimison, et al

Western Sydney University

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Article number	1199
Number of pages	11
Journal	BMC Cancer
Volume	21
DOIs	https://doi.org/10.1186/s12885-021-08952-9
Publication status	Published - 2021

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© The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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10.1186/s12885-021-08952-9

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Liu, D., Sharbeen, G., Phillips, P., Ford, C. E., Johns, A. L., Gill, A. L., Chantrill, L. A., Timpson, P., Chou, A., Pajic, M., Dwarte, T., Herrmann, D., Vennin, C., Cox, T. R., Pereira, B., Ritchie, S., Reed, D. A., Chambers, C. R., Metcalf, X., ... et al (2021). ROR1 and ROR2 expression in pancreatic cancer. BMC Cancer, 21, Article 1199. https://doi.org/10.1186/s12885-021-08952-9

@article{d07eff95965c4ed5a1ce234c27be5f89,

title = "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 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.",

author = "Dongli Liu and George Sharbeen and Phoebe Phillips and Ford, {Caroline E.} and Johns, {Amber L.} and Gill, {Amber L.} and Chantrill, {Lorraine A.} and Paul Timpson and Angela Chou and Marina Pajic and Tanya Dwarte and David Herrmann and Claire Vennin and Cox, {Thomas R.} and Brooke Pereira and Shona Ritchie and Reed, {Daniel A.} and Chambers, {Cecilia R.} and Xanthe Metcalf and Max Nobis and Nicola Waddell and Pearson, {John V.} and AnnMarie Patch and Katia Nones and Felicity Newell and Pamela Mukhopadhyay and Venkateswar Addala and Stephen Kazakoff and Oliver Holmes and Conrad Leonard and Scott Wood and Grimmond, {Sean M.} and Oliver Hofmann and Samra, {Jaswinder S.} and Nick Pavlakis and Jennifer Arena and High, {Hilda A.} and Ray Asghari and Merrett, {Neil D.} and Amitabha Das and Cosman, {Peter H.} and Kasim Ismail and Alina Stoita and David Williams and Allan Spigellman and Lam, {Vincent W.} and Duncan McLeod and Judy Kirk and Kench, {James G.} and Peter Grimison and {et al}",

year = "2021",

doi = "10.1186/s12885-021-08952-9",

language = "English",

volume = "21",

journal = "BMC Cancer",

issn = "1471-2407",

publisher = "BioMed Central",

}

Liu, D, Sharbeen, G, Phillips, P, Ford, CE, Johns, AL, Gill, AL, Chantrill, LA, Timpson, P, Chou, A, Pajic, M, Dwarte, T, Herrmann, D, Vennin, C, Cox, TR, Pereira, B, Ritchie, S, Reed, DA, Chambers, CR, Metcalf, X, Nobis, M, Waddell, N, Pearson, JV, Patch, A, Nones, K, Newell, F, Mukhopadhyay, P, Addala, V, Kazakoff, S, Holmes, O, Leonard, C, Wood, S, Grimmond, SM, Hofmann, O, Samra, JS, Pavlakis, N, Arena, J, High, HA, Asghari, R, Merrett, ND, Das, A, Cosman, PH, Ismail, K, Stoita, A, Williams, D, Spigellman, A, Lam, VW, McLeod, D, Kirk, J, Kench, JG, Grimison, P & et al 2021, 'ROR1 and ROR2 expression in pancreatic cancer', BMC Cancer, vol. 21, 1199. https://doi.org/10.1186/s12885-021-08952-9

TY - JOUR

T1 - ROR1 and ROR2 expression in pancreatic cancer

AU - Liu, Dongli

AU - Sharbeen, George

AU - Phillips, Phoebe

AU - Ford, Caroline E.

AU - Johns, Amber L.

AU - Gill, Amber L.

AU - Chantrill, Lorraine A.

AU - Timpson, Paul

AU - Chou, Angela

AU - Pajic, Marina

AU - Dwarte, Tanya

AU - Herrmann, David

AU - Vennin, Claire

AU - Cox, Thomas R.

AU - Pereira, Brooke

AU - Ritchie, Shona

AU - Reed, Daniel A.

AU - Chambers, Cecilia R.

AU - Metcalf, Xanthe

AU - Nobis, Max

AU - Waddell, Nicola

AU - Pearson, John V.

AU - Patch, AnnMarie

AU - Nones, Katia

AU - Newell, Felicity

AU - Mukhopadhyay, Pamela

AU - Addala, Venkateswar

AU - Kazakoff, Stephen

AU - Holmes, Oliver

AU - Leonard, Conrad

AU - Wood, Scott

AU - Grimmond, Sean M.

AU - Hofmann, Oliver

AU - Samra, Jaswinder S.

AU - Pavlakis, Nick

AU - Arena, Jennifer

AU - High, Hilda A.

AU - Asghari, Ray

AU - Merrett, Neil D.

AU - Das, Amitabha

AU - Cosman, Peter H.

AU - Ismail, Kasim

AU - Stoita, Alina

AU - Williams, David

AU - Spigellman, Allan

AU - Lam, Vincent W.

AU - McLeod, Duncan

AU - Kirk, Judy

AU - Kench, James G.

AU - Grimison, Peter

AU - et al, null

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

UR - http://hdl.handle.net/1959.7/uws:63067

U2 - 10.1186/s12885-021-08952-9

DO - 10.1186/s12885-021-08952-9

M3 - Article

SN - 1471-2407

VL - 21

JO - BMC Cancer

JF - BMC Cancer

M1 - 1199

ER -

ROR1 and ROR2 expression in pancreatic cancer

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