Variation in bulk RNA-seq and estimated cell type proportion using deconvolution when comparing pancreatic cancer...

Area of Science:

• Oncology
• Genomics
• Bioinformatics

Background:

• Genomic data holds promise for personalized cancer treatment.
• Intratumor genetic heterogeneity necessitates understanding variations within a tumor.
• Assessing gene expression across multiple tumor samples is crucial for treatment strategy.

Purpose of the Study:

• To investigate if tumor gene expression analysis interpretation varies between two specimens from the same patient.
• To compare cell type proportions and gene expression reliability across paired tumor samples.

Main Methods:

• Bulk RNA-sequencing was performed on FFPE samples from 16 patients.
• Three deconvolution methods were used to compare cell type proportions.
• Transcripts per million normalization and batch effect adjustment were applied for gene expression comparison.

Main Results:

• Significant variations in average cell type proportions were observed for NK cells and macrophages between samples.
• No significant differences in average expression were found for selected key pancreatic cancer genes.
• Concordance in gene expression measurements varied, with substantial agreement only for JUN.

Conclusions:

• Findings suggest that multiple tumor samples may be required for effective cancer treatment planning.
• Differences in observed expression values could be attributed to varying cell type proportions.
• Further studies are needed to confirm interpretations due to small sample size and different sequencing technologies.