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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-11-01
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| Series: | BMC Cancer |
| Online Access: | https://doi.org/10.1186/s12885-021-08952-9 |
| _version_ | 1818926802852118528 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T03:02:55Z |
| format | Article |
| id | doaj.art-77c1d36dfb864511964d2a94105709b4 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-20T03:02:55Z |
| publishDate | 2021-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-77c1d36dfb864511964d2a94105709b42022-12-21T19:55:41ZengBMCBMC Cancer1471-24072021-11-0121111110.1186/s12885-021-08952-9ROR1 and ROR2 expression in pancreatic cancerDongli Liu0George Sharbeen1Phoebe Phillips2Australian Pancreatic Cancer Genome Initiative3Caroline E. Ford4Gynaecological Cancer Research Group, Lowy Cancer Research Centre, School of Women’s and Children’s Health, Faculty of Medicine & Health, University of New South WalesPancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, School of Medical Science, Faculty of Medicine & Health, University of New South WalesPancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, School of Medical Science, Faculty of Medicine & Health, University of New South WalesAustralian Pancreatic Cancer Genome Initiative (APGI)Gynaecological Cancer Research Group, Lowy Cancer Research Centre, School of Women’s and Children’s Health, Faculty of Medicine & Health, University of New South WalesAbstract 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.https://doi.org/10.1186/s12885-021-08952-9 |
| spellingShingle | Dongli Liu George Sharbeen Phoebe Phillips Australian Pancreatic Cancer Genome Initiative Caroline E. Ford ROR1 and ROR2 expression in pancreatic cancer BMC Cancer |
| title | 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_short | ROR1 and ROR2 expression in pancreatic cancer |
| title_sort | ror1 and ror2 expression in pancreatic cancer |
| url | https://doi.org/10.1186/s12885-021-08952-9 |
| work_keys_str_mv | AT dongliliu ror1andror2expressioninpancreaticcancer AT georgesharbeen ror1andror2expressioninpancreaticcancer AT phoebephillips ror1andror2expressioninpancreaticcancer AT australianpancreaticcancergenomeinitiative ror1andror2expressioninpancreaticcancer AT carolineeford ror1andror2expressioninpancreaticcancer |