Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Serine-arginine protein kinase 1 (SRPK1) is under-expressed in mucinous colorectal cancer, and may mediate resistance to oxaliplatin

Duggan, William P ; Azimi, Mohammedreza ; Flanagan, Lyndsey ; Sullivan, Graeme P ; Reynolds, Ian S ; Fay, Joanna ; Dussmann, Heiko ; Ní Chonghaile, Tríona ; Sheehan, Katherine M and Jirström, Karin LU orcid , et al. (2025) In Pharmacogenomics Journal 25(5). p.1-10
Abstract

5-15% of all colorectal cancers (CRCs) are mucinous. Mucinous CRCs are associated with an inhibited response to standard adjuvant and neoadjuvant therapies. Serine-Arginine Protein Kinase 1 (SRPK1) is an enzyme, which modulates the activity of multiple splicing factors. SRPK1 under-expression is associated with resistance to platinum-based chemotherapeutic agents in multiple tumor types. The objectives of this study were to evaluate SRPK1 expression in mucinous CRC and to explore the potential relationship between differential SRPK1 expression and oxaliplatin resistance in mucinous CRC. Rectal cancer and CRC Tissue Microarrays (TMA) were stained with SRPK1 to compare expression between mucinous and non-mucinous tumors. SRPK1 expression... (More)

5-15% of all colorectal cancers (CRCs) are mucinous. Mucinous CRCs are associated with an inhibited response to standard adjuvant and neoadjuvant therapies. Serine-Arginine Protein Kinase 1 (SRPK1) is an enzyme, which modulates the activity of multiple splicing factors. SRPK1 under-expression is associated with resistance to platinum-based chemotherapeutic agents in multiple tumor types. The objectives of this study were to evaluate SRPK1 expression in mucinous CRC and to explore the potential relationship between differential SRPK1 expression and oxaliplatin resistance in mucinous CRC. Rectal cancer and CRC Tissue Microarrays (TMA) were stained with SRPK1 to compare expression between mucinous and non-mucinous tumors. SRPK1 expression was analyzed in mucinous and non-mucinous CRC cell lines. Cells were treated with oxaliplatin to explore differences in treatment response. Mucinous cells were transfected with an SRPK1 CRISPR/Cas9 lentiviral activation plasmid to investigate the relationship between SRPK1 expression and oxaliplatin resistance. The TMA cohorts included 117 patients with mucinous and 441 patients with non-mucinous CRC. SRPK1 was found to be under-expressed in both the mucinous rectal cancer (P < 0.001) and CRC cohorts (P = 0.003). On univariate analysis, SRPK1 under-expression was found to be associated with worse 5-year OS (P = 0.001). Treatment of mucinous CRC cells with oxaliplatin did not result in a significant increase in cell death (P = 0.149). However overexpression of SRPK1 following transfection with a CRISPR/CAS9 activation plasmid resulted in a significant increase in sensitivity of these cells to oxaliplatin treatment (P = 0.029). SRPK1 is under-expressed in mucinous CRC, and under-expression is associated with worse OS. This may be due to the positive effects of SRPK1 on oxaliplatin sensitivity.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Oxaliplatin/therapeutic use, Drug Resistance, Neoplasm/genetics, Colorectal Neoplasms/drug therapy, Male, Female, Adenocarcinoma, Mucinous/drug therapy, Protein Serine-Threonine Kinases/genetics, Middle Aged, Antineoplastic Agents/therapeutic use, Cell Line, Tumor, Aged, Gene Expression Regulation, Neoplastic, Tissue Array Analysis
in
Pharmacogenomics Journal
volume
25
issue
5
article number
26
pages
1 - 10
publisher
Springer Nature
external identifiers
  • pmid:41044076
ISSN
1470-269X
DOI
10.1038/s41397-025-00384-z
language
English
LU publication?
yes
additional info
© 2025. The Author(s), under exclusive licence to Springer Nature Limited.
id
7e10339f-143e-428f-936b-91b4e07de957
date added to LUP
2025-10-06 07:03:12
date last changed
2025-10-06 08:01:54
@article{7e10339f-143e-428f-936b-91b4e07de957,
  abstract     = {{<p>5-15% of all colorectal cancers (CRCs) are mucinous. Mucinous CRCs are associated with an inhibited response to standard adjuvant and neoadjuvant therapies. Serine-Arginine Protein Kinase 1 (SRPK1) is an enzyme, which modulates the activity of multiple splicing factors. SRPK1 under-expression is associated with resistance to platinum-based chemotherapeutic agents in multiple tumor types. The objectives of this study were to evaluate SRPK1 expression in mucinous CRC and to explore the potential relationship between differential SRPK1 expression and oxaliplatin resistance in mucinous CRC. Rectal cancer and CRC Tissue Microarrays (TMA) were stained with SRPK1 to compare expression between mucinous and non-mucinous tumors. SRPK1 expression was analyzed in mucinous and non-mucinous CRC cell lines. Cells were treated with oxaliplatin to explore differences in treatment response. Mucinous cells were transfected with an SRPK1 CRISPR/Cas9 lentiviral activation plasmid to investigate the relationship between SRPK1 expression and oxaliplatin resistance. The TMA cohorts included 117 patients with mucinous and 441 patients with non-mucinous CRC. SRPK1 was found to be under-expressed in both the mucinous rectal cancer (P &lt; 0.001) and CRC cohorts (P = 0.003). On univariate analysis, SRPK1 under-expression was found to be associated with worse 5-year OS (P = 0.001). Treatment of mucinous CRC cells with oxaliplatin did not result in a significant increase in cell death (P = 0.149). However overexpression of SRPK1 following transfection with a CRISPR/CAS9 activation plasmid resulted in a significant increase in sensitivity of these cells to oxaliplatin treatment (P = 0.029). SRPK1 is under-expressed in mucinous CRC, and under-expression is associated with worse OS. This may be due to the positive effects of SRPK1 on oxaliplatin sensitivity.</p>}},
  author       = {{Duggan, William P and Azimi, Mohammedreza and Flanagan, Lyndsey and Sullivan, Graeme P and Reynolds, Ian S and Fay, Joanna and Dussmann, Heiko and Ní Chonghaile, Tríona and Sheehan, Katherine M and Jirström, Karin and Prehn, Jochen H M and Burke, John P}},
  issn         = {{1470-269X}},
  keywords     = {{Humans; Oxaliplatin/therapeutic use; Drug Resistance, Neoplasm/genetics; Colorectal Neoplasms/drug therapy; Male; Female; Adenocarcinoma, Mucinous/drug therapy; Protein Serine-Threonine Kinases/genetics; Middle Aged; Antineoplastic Agents/therapeutic use; Cell Line, Tumor; Aged; Gene Expression Regulation, Neoplastic; Tissue Array Analysis}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{5}},
  pages        = {{1--10}},
  publisher    = {{Springer Nature}},
  series       = {{Pharmacogenomics Journal}},
  title        = {{Serine-arginine protein kinase 1 (SRPK1) is under-expressed in mucinous colorectal cancer, and may mediate resistance to oxaliplatin}},
  url          = {{http://dx.doi.org/10.1038/s41397-025-00384-z}},
  doi          = {{10.1038/s41397-025-00384-z}},
  volume       = {{25}},
  year         = {{2025}},
}