A TP53-associated immune prognostic signature for the prediction of the overall survival and therapeutic responses in pancreatic cancer
Open accessAbstract
Pancreatic cancer (PC) is a highly fatal disease correlated with an inferior prognosis. The tumor protein p53 (TP53) is one of the frequent mutant genes in PC and has been implicated in prognosis. We collected somatic mutation data, RNA sequencing data, and clinical information of PC samples in the Cancer Genome Atlas (TCGA) database. TP53 mutation was an independent prognostic predictor of PC patients. According to TP53 status, Gene set enrichment analysis (GSEA) suggested that TP53 mutations were related to the immunophenotype of pancreatic cancer. We identified 102 differentially expressed immune genes (DEIGs) based on TP53 mutation status and developed a TP53-associated immune prognostic model (TIPM), including Epiregulin (EREG) and Prolactin receptor (PRLR). TIPM identified the high-risk group with poor outcomes and more significant response potential to cisplatin, gemcitabine, and paclitaxel therapies. And we verified the TIPM in the International Cancer Genome Consortium (ICGC) cohort (PACA-AU) and Gene Expression Omnibus (GEO) cohort (GSE78229 and GSE28735). Finally, we developed a nomogram that reliably predicts overall survival in PC patients on the bias of TIPM and other clinicopathological factors. Our study indicates that the TIPM derived from TP53 mutation patterns might be an underlying prognostic therapeutic target. But more comprehensive researches with a large sample size is necessary to confirm the potential.
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The TP53 mutational status-based genomic signature has independent predictive value for overall survival and good prognostic estimate in pancreatic cancer patients.
“Studies demonstrate its independent predictive value for overall survival and good prognostic estimate in pancreatic cancer patients.”
From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [22]
The accuracy of the TP53 genomic signature is underscored by its association with the immunophenotype of PDAC.
“The accuracy of this genomic signature is underscored by its association with the immunophenotype of PDAC [21,22,23].”
From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [22]
The TP53 mutational status-based genomic signature is a critical factor for disease prognosis and therapeutic responses.
“The TP53 mutational status-based genomic signature emerges as a critical factor for disease prognosis and therapeutic responses.”
From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [22]
Cites
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<i>STK11/LKB1</i> Mutations and PD-1 Inhibitor Resistance in <i>KRAS</i> -Mutant Lung Adenocarcinoma
Skoulidis, F., Goldberg, M. E., Greenawalt, D. M., Hellmann, M. D., Awad, M. M., Gainor, J. F., Schrock, A. B., Hartmaier, R. J., Trabucco, S. E., Gay, L., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0099 · Cited by 1,641 · see citing works
Self-citationWhole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets
Witkiewicz, A. K., McMillan, E. A., Balaji, U., Baek, G., Lin, W.-C., Mansour, J., Mollaee, M., Wagner, K.-U., Koduru, P., Yopp, A., et al. (2015) · Nature Communications · doi:10.1038/ncomms7744 · Cited by 1,115 · see citing works
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Targeting mutant p53 for efficient cancer therapy
Bykov, V. J. N., Eriksson, S. E., Bianchi, J., & Wiman, K. G. (2018) · Nature Reviews Cancer · doi:10.1038/nrc.2017.109 · Cited by 889 · see citing works
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Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer
Stefanoudakis, D., Frountzas, M., Schizas, D., Michalopoulos, N. V., Drakaki, A., & Toutouzas, K. G. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb46040177 · Cited by 110 · see citing works
- Authors
- Liu, Y., Department of Colorectal and Anal Surgery, T. F. H. O. J. U., Cheng, L., Song, X., Li, C., Zhang, J., Wang, L., Department of Orthopedics, T. F. H. O. J. U., & Department of Hepatobiliary and Pancreatic Surgery, T. F. H. O. J. U.
- Affiliations
- First Hospital of Jilin University (CN)
- Corresponding author
- Wang, Lei
- Venue
- Mathematical Biosciences and Engineering
- Published
- 2022
- Volume
- 19
- Issue
- 1
- Pages
- 191-208
- ISSN
- 1547-1063 (ISSN-L)
- 1551-0018
- OpenAlex
- W3212229335
- Cited by
- 14
- References
- 5
- Citations by year
- 2025: 8 · 2024: 2 · 2023: 1 · 2022: 3
- FWCI
- 0.55
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- Mathematical Biosciences & Engineering (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
- Keywords
- pancreatic cancer, TP53 mutation, tumor immune microenvironment, epiregulin, prolactin receptor, overall survival prediction, treatment response prediction, cisplatin, gemcitabine, paclitaxel, nomogram, prognostic model
- MeSH terms
- Humans, Mutation, Pancreatic Neoplasms, Prognosis, Tumor Suppressor Protein p53, Nomograms
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