Dataset Information

Identifying genetic expression patterns as marker for sensitivity to oncolytic viruses using patient-derived pancreatic ductal adenocarcinoma organoids

ABSTRACT: Purpose: Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers, with a poor prognosis. Viro-immunotherapy using oncolytic viruses (OVs) represents a promising treatment for PDAC. However, PDACs from different patients respond differently to OV therapies, highlighting the need for predictive biomarkers to optimize outcomes. This study aimed to identify gene expression profiles (GEPs) that could serve as predictors for OV sensitivity. Experimental design: Patient-derived organoids (PDOs) from ten PDAC patients were assessed for sensitivity to various OVs: Newcastle Disease Virus, a Reovirus strain entering cells independently of JAM-A expression, the Edmonston vaccine strain of Measles Virus, and a gorilla-derived adenovirus. To identify GEPs with predictive value, OV sensitivity was correlated with the transcriptome of uninfected PDOs. These GEPs were analyzed in the Gene Ontology database to reveal biological processes associated with them. Results: PDOs showed heterogenic responses to OVs, with nine of ten being sensitive to at least one. Analysis of the generated GEPs using the Gene Ontology database identified intracellular aberrations as the primary determinant of OV sensitivity. Sensitivity to all OVs was associated with GEPs related to embryonic development, while varied sensitivity of the ten PDOs to four OVs was linked to cell cycle regulation, metabolism, and proliferation. Conclusions: This study revealed that OV sensitivity was associated with GEPs comprising genes involved in multiple biological processes. Further investigation into screening tumors for the identified GEPs may yield biomarkers for selecting the most effective OV for PDAC. This approach is a stepping stone toward personalized OV treatments.

ORGANISM(S): Homo sapiens

PROVIDER: GSE288907 | GEO | 2025/02/11

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Recurrent non-medullary thyroid carcinoma (NMTC) is a rare disease. We initially characterized 27 recurrent NMTC: 13 papillary thyroid cancers (PTC), 10 oncocytic follicular carcinomas (FTC-OV), and 4 non-oncocytic follicular carcinomas (FTC). A validation cohort composed of benign and malignant (both recurrent and non-recurrent) thyroid tumours was subsequently analysed (n = 20). Methods Data from genome-wide SNP arrays and flow cytometry were combined to determine the chromosomal dosage (allelic state) in these tumours, including mutation analysis of components of PIK3CA/AKT and MAPK pathways. Results All FTC-OVs showed a very distinct pattern of genomic alterations. Ten out of 10 FTC-OV cases showed near-haploidisation with or without subsequent genome endoreduplication. Near-haploidisation was seen in 5/10 as extensive chromosome-wide monosomy (allelic state [A]) with near-haploid DNA indices and retention of especially chromosome 7 (seen as a heterozygous allelic state [AB]). In the remaining 5/10 chromosomal allelic states AA with near diploid DNA indices were seen with allelic state AABB of chromosome 7, suggesting endoreduplication after preceding haploidisation. The latter was supported by the presence of both near-haploid and endoreduplicated tumour fractions in some of the cases. Results were confirmed using FISH analysis. Relatively to FTC-OV limited numbers of genomic alterations were identified in other types of recurrent NMTC studied, except for chromosome 22q which showed alterations in 6 of 13 PTCs. Only two HRAS, but no mutations of EGFR or BRAF were found in FTC-OV. The validation cohort showed two additional tumours with the distinct pattern of genomic alterations (both with oncocytic features and recurrent). Conclusions We demonstrate that recurrent FTC-OV is frequently characterised by genome-wide DNA haploidisation, heterozygous retention of chromosome 7, and endoreduplication of a near-haploid genome. Whether normal gene dosage on especially chromosome 7 (containing EGFR, BRAF, cMET) is crucial for FTC-OV tumour survival is an important topic for future research. 28 thyroid tumors from 27 patients were profiled by SNP array. Comparisons between different types were made.

Dataset Information

Identifying genetic expression patterns as marker for sensitivity to oncolytic viruses using patient-derived pancreatic ductal adenocarcinoma organoids

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets