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PRR11 unveiled as a top candidate biomarker within the RBM3-regulated transcriptome in pancreatic cancer

Olsson Hau, Sofie LU ; Wahlin, Sara LU ; Cervin, Sophie ; Falk, Vilgot ; Nodin, Björn LU ; Elebro, Jacob LU ; Eberhard, Jakob LU ; Moran, Bruce ; Gallagher, William M. and Karnevi, Emelie LU , et al. (2022) In Journal of Pathology: Clinical Research 8(1). p.65-77
Abstract

The outlook for patients with pancreatic cancer remains dismal. Treatment options are limited and chemotherapy remains standard of care, leading to only modest survival benefits. Hence, there is a great need to further explore the mechanistic basis for the intrinsic therapeutic resistance of this disease, and to identify novel predictive biomarkers. RNA-binding motif protein 3 (RBM3) has emerged as a promising biomarker of disease severity and chemotherapy response in several types of cancer, including pancreatic cancer. The aim of this study was to unearth RBM3-regulated genes and proteins in pancreatic cancer cells in vitro, and to examine their expression and prognostic significance in human tumours. Next-generation RNA sequencing... (More)

The outlook for patients with pancreatic cancer remains dismal. Treatment options are limited and chemotherapy remains standard of care, leading to only modest survival benefits. Hence, there is a great need to further explore the mechanistic basis for the intrinsic therapeutic resistance of this disease, and to identify novel predictive biomarkers. RNA-binding motif protein 3 (RBM3) has emerged as a promising biomarker of disease severity and chemotherapy response in several types of cancer, including pancreatic cancer. The aim of this study was to unearth RBM3-regulated genes and proteins in pancreatic cancer cells in vitro, and to examine their expression and prognostic significance in human tumours. Next-generation RNA sequencing was applied to compare transcriptomes of MIAPaCa-2 cells with and without RBM3 knockdown. The prognostic value of differentially expressed genes (DEGs) was examined in The Cancer Genome Atlas (TCGA). Top deregulated genes were selected for further studies in vitro and for immunohistochemical analysis of corresponding protein expression in tumours from a clinically well-annotated consecutive cohort of 46 patients with resected pancreatic cancer. In total, 19 DEGs (p < 0.01) were revealed, among which some with functions in cell cycle and cell division stood out; PDS5A (PDS cohesin associated factor A) as the top downregulated gene, CCND3 (cyclin D3) as the top upregulated gene, and PRR11 (proline rich 11) as being highly prognostic in TCGA. Silencing of RBM3 in MiaPaCa-2 cells led to congruent alterations of PDS5A, cyclin D3, and PRR11 levels. High protein expression of PRR11 was associated with adverse clinicopathological features and shorter overall survival. Neither PDS5A nor cyclin D3 protein expression was prognostic. This study unveils several RBM3-regulated genes with potential clinical relevance in pancreatic cancer, among which PRR11 shows the most consistent association with disease severity, at both transcriptome and protein levels.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cyclin D3, pancreatic cancer, PDS5A, prognosis, PRR11, RBM3-regulated genes
in
Journal of Pathology: Clinical Research
volume
8
issue
1
pages
65 - 77
publisher
Wiley-Blackwell
external identifiers
  • scopus:85112363386
  • pmid:34379360
ISSN
2056-4538
DOI
10.1002/cjp2.238
project
Disease and illness trajectories of pancreatic cancer
language
English
LU publication?
yes
id
3891345f-3462-4bbe-84cb-8d4bfc276de5
date added to LUP
2021-09-17 13:07:21
date last changed
2024-06-15 16:30:36
@article{3891345f-3462-4bbe-84cb-8d4bfc276de5,
  abstract     = {{<p>The outlook for patients with pancreatic cancer remains dismal. Treatment options are limited and chemotherapy remains standard of care, leading to only modest survival benefits. Hence, there is a great need to further explore the mechanistic basis for the intrinsic therapeutic resistance of this disease, and to identify novel predictive biomarkers. RNA-binding motif protein 3 (RBM3) has emerged as a promising biomarker of disease severity and chemotherapy response in several types of cancer, including pancreatic cancer. The aim of this study was to unearth RBM3-regulated genes and proteins in pancreatic cancer cells in vitro, and to examine their expression and prognostic significance in human tumours. Next-generation RNA sequencing was applied to compare transcriptomes of MIAPaCa-2 cells with and without RBM3 knockdown. The prognostic value of differentially expressed genes (DEGs) was examined in The Cancer Genome Atlas (TCGA). Top deregulated genes were selected for further studies in vitro and for immunohistochemical analysis of corresponding protein expression in tumours from a clinically well-annotated consecutive cohort of 46 patients with resected pancreatic cancer. In total, 19 DEGs (p &lt; 0.01) were revealed, among which some with functions in cell cycle and cell division stood out; PDS5A (PDS cohesin associated factor A) as the top downregulated gene, CCND3 (cyclin D3) as the top upregulated gene, and PRR11 (proline rich 11) as being highly prognostic in TCGA. Silencing of RBM3 in MiaPaCa-2 cells led to congruent alterations of PDS5A, cyclin D3, and PRR11 levels. High protein expression of PRR11 was associated with adverse clinicopathological features and shorter overall survival. Neither PDS5A nor cyclin D3 protein expression was prognostic. This study unveils several RBM3-regulated genes with potential clinical relevance in pancreatic cancer, among which PRR11 shows the most consistent association with disease severity, at both transcriptome and protein levels.</p>}},
  author       = {{Olsson Hau, Sofie and Wahlin, Sara and Cervin, Sophie and Falk, Vilgot and Nodin, Björn and Elebro, Jacob and Eberhard, Jakob and Moran, Bruce and Gallagher, William M. and Karnevi, Emelie and Jirström, Karin}},
  issn         = {{2056-4538}},
  keywords     = {{cyclin D3; pancreatic cancer; PDS5A; prognosis; PRR11; RBM3-regulated genes}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{65--77}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of Pathology: Clinical Research}},
  title        = {{PRR11 unveiled as a top candidate biomarker within the RBM3-regulated transcriptome in pancreatic cancer}},
  url          = {{http://dx.doi.org/10.1002/cjp2.238}},
  doi          = {{10.1002/cjp2.238}},
  volume       = {{8}},
  year         = {{2022}},
}