How mutations affect mRNA and protein levels in cancer
Author Information
Author(s): Yuqi Liu, Abdulkadir Elmas, Kuan-lin Huang
Primary Institution: Icahn School of Medicine at Mount Sinai
Hypothesis
How do somatic mutations affect protein expression in addition to gene expression across different cancer types?
Conclusion
Somatic mutations can have distinct impacts on mRNA and protein levels, highlighting the importance of integrating proteogenomic data for identifying functionally significant cancer mutations.
Supporting Evidence
- 47.2% of somatic expression quantitative trait loci (seQTLs) were validated for protein-level impacts.
- TP53 missense mutations were associated with higher protein expression in multiple cancer cohorts.
- Significant enrichment for truncations was found in protein quantitative trait loci (pQTLs).
- Concordant effects were observed in 88.9% of significant seQTLs and spQTLs.
Takeaway
This study looks at how changes in genes from cancer can affect both the messages that tell cells to make proteins and the proteins themselves, which can be different.
Methodology
The study used proteogenomic datasets from 953 cancer cases with paired genomics and proteomic profiling across 6 cancer types, applying multiple regression analyses to identify significant gene-cancer pairs.
Potential Biases
Potential biases may arise from the reliance on FDR thresholds and the assumption of linear relationships in regression models.
Limitations
The study does not distinguish between mechanisms leading to discordant effects of mutations on gene and protein expression and is limited by sample sizes and the linear regression model used.
Participant Demographics
The study included diverse cancer types, with specific sample sizes for each type, but detailed demographics were not provided.
Statistical Information
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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