# Effectors and potential targets selectively upregulated in human KRAS-mutant lung adenocarcinomas

## TL;DR

This study identifies proteins and genes that are more active in lung cancer tumors with KRAS mutations, highlighting potential new treatment targets.

## Contribution

The study identifies new potential therapeutic targets and effectors specifically upregulated in KRAS-mutant lung adenocarcinomas.

## Key findings

- KRAS-mutant tumors show stronger activation of Raf/MAPK signaling components compared to other tumor types.
- Genes like PTPRE and activators of Rac/Rho proteins are strongly upregulated in KRAS-mutant tumors.
- Differential activation of PDK1 and PKC-alpha is associated with co-occurring mutations in KRAS-mutant tumors.

## Abstract

Genetic and proteomic analysis of human tumor samples can provide an important compliment to information obtained from model systems. Here we examined protein and gene expression from the Cancer Genome and Proteome Atlases (TCGA and TCPA) to characterize proteins and protein-coding genes that are selectively upregulated in KRAS-mutant lung adenocarcinomas. Phosphoprotein activation of several Raf/MAPK signaling components was considerably stronger in KRAS-mutants than any other group of tumors. However, both KRAS-mutants and tumors with other activating mutations in the Raf/MAPK pathway showed comparable activation of mTOR. Co-occurring mutations in KRAS-mutants were associated with differential activation of PDK1 and PKC-alpha. Genes showing strong activation in RNA-seq data included negative regulators of Raf/MAPK signaling along with potential oncogenic effectors including activators of Rac and Rho proteins and the receptor protein-tyrosine phosphatase gene PTPRE. These results corroborate Raf/MAPK signaling as an important therapeutic target in KRAS-mutant lung adenocarcinomas and pinpoint new potential targets.