Transcriptomic Analysis of Laser Capture Microdissected Tumors of Pancreatic Ductal Adenocarcinoma

ABSTRACT: 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-seq analysis of cancer and adjacent stroma of 19 treatment-naïve PDAC tumors were performed. Gene expression signatures were tested for their robustness in a large independent validation set. An RNA in situ hybridization (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 (p=5.55E-07), with S1 associated with better prognoses when paired with C1 and C2. Thirteen genes were found to be predominantly expressed in cancer cells and corresponded with DFS in a validation using existing RNA-seq datasets. A second validation on an independent cohort of patients using RNA-ISH probes to six of these prognostic genes demonstrated significant association with overall survival (median 17 versus 25 months; p<0.02). 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE164665 | GEO | 2021/06/30

REPOSITORIES: GEO