Transcriptomic Analysis of Laser Capture Microdissected Tumors Reveals Cancer- and Stromal-Specific Molecular Subtypes of Pancreatic Ductal Adenocarcinoma.
Aged
Biomarkers, Tumor
/ genetics
Carcinoma, Pancreatic Ductal
/ genetics
Datasets as Topic
Disease-Free Survival
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Humans
Laser Capture Microdissection
Male
Middle Aged
Pancreas
/ pathology
Pancreatectomy
Pancreatic Neoplasms
/ genetics
Prognosis
RNA-Seq
Risk Assessment
/ methods
Stromal Cells
/ pathology
Tumor Microenvironment
/ genetics
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
15 04 2021
15 04 2021
Historique:
received:
24
03
2020
revised:
22
11
2020
accepted:
01
02
2021
pubmed:
7
2
2021
medline:
15
3
2022
entrez:
6
2
2021
Statut:
ppublish
Résumé
Pancreatic ductal adenocarcinoma (PDAC) lethality is multifactorial; although studies have identified transcriptional and genetic subsets of tumors with different prognostic significance, there is limited understanding of features associated with the minority of patients who have durable remission after surgical resection. In this study, we performed laser capture microdissection (LCM) of PDAC samples to define their cancer- and stroma-specific molecular subtypes and identify a prognostic gene expression signature for short-term and long-term survival. LCM and RNA sequencing (RNA-seq) analysis of cancer and adjacent stroma of 19 treatment-naïve PDAC tumors was performed. Gene expression signatures were tested for their robustness in a large independent validation set. An RNA-ISH assay with pooled probes for genes associated with disease-free survival (DFS) was developed to probe 111 PDAC tumor samples. Gene expression profiling identified four subtypes of cancer cells (C1-C4) and three subtypes of cancer-adjacent stroma (S1-S3). These stroma-specific subtypes were associated with DFS ( Our results identified specific signatures from the epithelial and the stroma components of PDAC, which add clarity to the nature of PDAC molecular subtypes and may help predict survival.
Identifiants
pubmed: 33547202
pii: 1078-0432.CCR-20-1039
doi: 10.1158/1078-0432.CCR-20-1039
pmc: PMC8118131
mid: NIHMS1672815
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Validation Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
2314-2325Subventions
Organisme : NCI NIH HHS
ID : R01 CA235412
Pays : United States
Organisme : NCI NIH HHS
ID : R03 CA241971
Pays : United States
Informations de copyright
©2021 American Association for Cancer Research.
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