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Anoikis-related genes linked with patient outcome in pancreatic cancer

Lin, Lizhi LU ; Deng, Jing ; Yu, Jiaye ; Bauden, Monika LU orcid ; Andersson, Roland LU ; Shen, Xian ; Ansari, Daniel LU and Xue, Xiangyang (2024) In Gene 930.
Abstract

Anoikis is programmed cell death occurring upon cell detachment from the extracellular matrix. Cancer cells need to evade anoikis to be able to metastasize to distant sites. However, the molecular features and prognostic value of anoikis-related genes (ARGs) in pancreatic cancer remain unclear. In this study, we utilized transcriptome data from the TCGA and GSE102238 databases to identify 64 ARGs significantly associated with prognosis. We used the "ConsensusClusterPlus" R package to stratify patients into high and low-risk prognostic subgroups. The KEGG and GSEA analyses revealed that the clusters with poor prognosis were enriched for the ECM receptor interaction pathway, the TP53 signaling pathway, and the galactose metabolism... (More)

Anoikis is programmed cell death occurring upon cell detachment from the extracellular matrix. Cancer cells need to evade anoikis to be able to metastasize to distant sites. However, the molecular features and prognostic value of anoikis-related genes (ARGs) in pancreatic cancer remain unclear. In this study, we utilized transcriptome data from the TCGA and GSE102238 databases to identify 64 ARGs significantly associated with prognosis. We used the "ConsensusClusterPlus" R package to stratify patients into high and low-risk prognostic subgroups. The KEGG and GSEA analyses revealed that the clusters with poor prognosis were enriched for the ECM receptor interaction pathway, the TP53 signaling pathway, and the galactose metabolism pathway, and that the cell cycle pathway was upregulated. A prognostic model consisting of seven ARGs (SERPINE1, EGF, E2F1, MSLN, RAB27B, ETV7, MST1) was constructed using LASSO regression and when combined with clinicopathological parameters using Cox regression, a prognostic Nomogram was created, which demonstrated high prognostic utility. Among the biomarker candidates, we report ETV7 as a novel, independent prognostic marker in pancreatic cancer. ETV7 was highly expressed in KRAS and TP53 co-occurrent mutant TCGA patients, indicating that it may be regulated by the two major driver genes of pancreatic cancer. Therefore, targeting ETV7 could be a potential focus for future therapeutic studies.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Pancreatic Neoplasms/genetics, Anoikis/genetics, Prognosis, Biomarkers, Tumor/genetics, Gene Expression Regulation, Neoplastic, Male, Transcriptome, Female, Tumor Suppressor Protein p53/genetics, Gene Expression Profiling/methods, Nomograms, Proto-Oncogene Proteins p21(ras)/genetics
in
Gene
volume
930
article number
148868
publisher
Elsevier
external identifiers
  • pmid:39154969
  • scopus:85201472712
ISSN
0378-1119
DOI
10.1016/j.gene.2024.148868
language
English
LU publication?
yes
additional info
Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.
id
c122c6a2-9a0f-4315-affc-fa275198286f
date added to LUP
2024-09-12 10:19:36
date last changed
2024-12-20 16:14:38
@article{c122c6a2-9a0f-4315-affc-fa275198286f,
  abstract     = {{<p>Anoikis is programmed cell death occurring upon cell detachment from the extracellular matrix. Cancer cells need to evade anoikis to be able to metastasize to distant sites. However, the molecular features and prognostic value of anoikis-related genes (ARGs) in pancreatic cancer remain unclear. In this study, we utilized transcriptome data from the TCGA and GSE102238 databases to identify 64 ARGs significantly associated with prognosis. We used the "ConsensusClusterPlus" R package to stratify patients into high and low-risk prognostic subgroups. The KEGG and GSEA analyses revealed that the clusters with poor prognosis were enriched for the ECM receptor interaction pathway, the TP53 signaling pathway, and the galactose metabolism pathway, and that the cell cycle pathway was upregulated. A prognostic model consisting of seven ARGs (SERPINE1, EGF, E2F1, MSLN, RAB27B, ETV7, MST1) was constructed using LASSO regression and when combined with clinicopathological parameters using Cox regression, a prognostic Nomogram was created, which demonstrated high prognostic utility. Among the biomarker candidates, we report ETV7 as a novel, independent prognostic marker in pancreatic cancer. ETV7 was highly expressed in KRAS and TP53 co-occurrent mutant TCGA patients, indicating that it may be regulated by the two major driver genes of pancreatic cancer. Therefore, targeting ETV7 could be a potential focus for future therapeutic studies.</p>}},
  author       = {{Lin, Lizhi and Deng, Jing and Yu, Jiaye and Bauden, Monika and Andersson, Roland and Shen, Xian and Ansari, Daniel and Xue, Xiangyang}},
  issn         = {{0378-1119}},
  keywords     = {{Humans; Pancreatic Neoplasms/genetics; Anoikis/genetics; Prognosis; Biomarkers, Tumor/genetics; Gene Expression Regulation, Neoplastic; Male; Transcriptome; Female; Tumor Suppressor Protein p53/genetics; Gene Expression Profiling/methods; Nomograms; Proto-Oncogene Proteins p21(ras)/genetics}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Gene}},
  title        = {{Anoikis-related genes linked with patient outcome in pancreatic cancer}},
  url          = {{http://dx.doi.org/10.1016/j.gene.2024.148868}},
  doi          = {{10.1016/j.gene.2024.148868}},
  volume       = {{930}},
  year         = {{2024}},
}