Single-cell transcriptome reveals the heterogeneity of malignant ductal cells and the prognostic value of REG4 and SPINK1 in primary pancreatic ductal adenocarcinoma.
Humans
Carcinoma, Pancreatic Ductal
/ genetics
Trypsin Inhibitor, Kazal Pancreatic
/ genetics
Pancreatic Neoplasms
/ genetics
Prognosis
Single-Cell Analysis
Transcriptome
Lectins, C-Type
/ genetics
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
Biomarkers, Tumor
/ genetics
Female
Male
Pancreatitis-Associated Proteins
Ductal cell
Immune microenvironment
Metabolic reprogramming
Pancreatic ductal adenocarcinoma
Prognostic biomarker
Single-cell transcriptome
Journal
PeerJ
ISSN: 2167-8359
Titre abrégé: PeerJ
Pays: United States
ID NLM: 101603425
Informations de publication
Date de publication:
2024
2024
Historique:
received:
12
12
2023
accepted:
17
04
2024
medline:
3
6
2024
pubmed:
3
6
2024
entrez:
3
6
2024
Statut:
epublish
Résumé
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related deaths, with very limited therapeutic options available. This study aims to comprehensively depict the heterogeneity and identify prognostic targets for PDAC with single-cell RNA sequencing (scRNA-seq) analysis. ScRNA-seq analysis was performed on 16 primary PDAC and three adjacent lesions. A series of analytical methods were applied for analysis in cell clustering, gene profiling, lineage trajectory analysis and cell-to-cell interactions. A total of 32,480 cells were clustered into six major populations, among which the ductal cell cluster expressing high copy number variants (CNVs) was defined as malignant cells. Malignant cells were further subtyped into five subgroups which exhibited specific features in immunologic and metabolic activities. Pseudotime trajectory analysis indicated that components of various oncogenic pathways were differentially expressed along tumor progression. Furthermore, intensive substantial crosstalk between ductal cells and stromal cells was identified. Finally, genes (REG4 and SPINK1) screened out of differentially expressed genes (DEGs) were upregulated in PDAC cell lines. Silencing either of them significantly impaired proliferation, invasion, migration and stemness of PDAC cells. Our findings offer a valuable resource for deciphering the heterogeneity of malignant ductal cells in PDAC. REG4 and SPINK1 are expected to be promising targets for PDAC therapy.
Sections du résumé
Background
UNASSIGNED
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related deaths, with very limited therapeutic options available. This study aims to comprehensively depict the heterogeneity and identify prognostic targets for PDAC with single-cell RNA sequencing (scRNA-seq) analysis.
Methods
UNASSIGNED
ScRNA-seq analysis was performed on 16 primary PDAC and three adjacent lesions. A series of analytical methods were applied for analysis in cell clustering, gene profiling, lineage trajectory analysis and cell-to-cell interactions.
Results
UNASSIGNED
A total of 32,480 cells were clustered into six major populations, among which the ductal cell cluster expressing high copy number variants (CNVs) was defined as malignant cells. Malignant cells were further subtyped into five subgroups which exhibited specific features in immunologic and metabolic activities. Pseudotime trajectory analysis indicated that components of various oncogenic pathways were differentially expressed along tumor progression. Furthermore, intensive substantial crosstalk between ductal cells and stromal cells was identified. Finally, genes (REG4 and SPINK1) screened out of differentially expressed genes (DEGs) were upregulated in PDAC cell lines. Silencing either of them significantly impaired proliferation, invasion, migration and stemness of PDAC cells.
Conclusions
UNASSIGNED
Our findings offer a valuable resource for deciphering the heterogeneity of malignant ductal cells in PDAC. REG4 and SPINK1 are expected to be promising targets for PDAC therapy.
Identifiants
pubmed: 38827297
doi: 10.7717/peerj.17350
pii: 17350
pmc: PMC11141562
doi:
Substances chimiques
SPINK1 protein, human
0
Trypsin Inhibitor, Kazal Pancreatic
50936-63-5
REG4 protein, human
0
Lectins, C-Type
0
Biomarkers, Tumor
0
Pancreatitis-Associated Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e17350Informations de copyright
©2024 Ji et al.
Déclaration de conflit d'intérêts
The authors declare there are no competing interests.