Bulk RNA-seq deconvolution heterogeneity across paired pancreatic cancer human samples

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 differences between tumor samples is crucial for treatment planning.

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.
• To evaluate the concordance of key gene expression in pancreatic cancer.

Main Methods:

• Bulk RNA-sequencing (RNA-seq) was performed on formalin-fixed paraffin-embedded (FFPE) samples from 16 patients.
• Three deconvolution methods were used to compare cell type proportions between paired samples.
• Transcripts per million (TPM) normalization and batch effect adjustment were applied for comparative analysis of gene expression.

Main Results:

• Significant variations in cell type proportions were observed for NK cells and macrophages between paired samples (adjusted p-value < 0.002).
• No significant differences in average expression were found for selected genes (KRAS, TP53, SMAD4, CDKN2A, CTNNB1, JUN, SMAD3, SMAD7, TCF7).
• Substantial concordance (kappa = 0.75) was observed for JUN, with low to moderate concordance for other genes.

Conclusions:

• Findings suggest that multiple tumor samples may be required for effective cancer treatment planning due to observed variations.
• Differences in expression values could be attributed to varying cell type proportions between samples.
• Further studies with larger sample sizes and consistent sequencing technologies are needed to confirm these interpretations.