The Functional Effects of Key Driver KRAS Mutations on Gene Expression in Lung Cancer.

Jisong Zhang,Hanliang Jiang,Jihong Zhu,Shan Xu,Zhengfu He,Huihui Hu,E Qin,Enguo Chen

doi:10.3389/fgene.2020.00017

Jisong Zhang, Hanliang Jiang + Show 6 more

Open Access

https://doi.org/10.3389/fgene.2020.00017

Copy DOI

Abstract

Lung cancer is a common malignant cancer. Kirsten rat sarcoma oncogene (KRAS) mutations have been considered as a key driver for lung cancers. KRAS p.G12C mutations were most predominant in NSCLC which was comprised about 11–16% of lung adenocarcinomas (p.G12C accounts for 45–50% of mutant KRAS). But it is still not clear how the KRAS mutation triggers lung cancers. To study the molecular mechanisms of KRAS mutation in lung cancer. We analyzed the gene expression profiles of 156 KRAS mutation samples and other negative samples with two stage feature selection approach: (1) minimal Redundancy Maximal Relevance (mRMR) and (2) Incremental Feature Selection (IFS). At last, 41 predictive genes for KRAS mutation were identified and a KRAS mutation predictor was constructed. Its leave one out cross validation MCC was 0.879. Our results were helpful for understanding the roles of KRAS mutation in lung cancer.

Highlights

Lung cancer, known as a malignant cancer which defined as the overgrowth of uncontrolled cell in lung tissues, has proved be a key cause of cancer death
Non-small-cell lung cancer (NSCLC) can be further divided into adenocarcinoma, squamous cell carcinoma (SCC), and large cell carcinoma (Sandler et al, 2006; Morgensztern et al, 2010)
Since the sizes of Kirsten rat sarcoma oncogene (KRAS) mutation + samples and KRAS mutation - samples were imbalance and Mathew’s correlation coefficient (MCC) can trade-off sensitivity and specificity (Chen et al, 2018a; Li et al, 2018; Pan et al, 2018; Pan et al, 2019a; Pan et al, 2019b), MCC was used as the main performance metric

Summary

INTRODUCTION

Known as a malignant cancer which defined as the overgrowth of uncontrolled cell in lung tissues, has proved be a key cause of cancer death. The pathogenesis of lung cancer is not very clear, but is generally believed that one of the most important reason is the accumulation of mutations including single nucleotide transformation, small fragments of insertions and deletions, the changes of copy number, and chromosome rearrangement. These mutations are closed with cell proliferation, invasion, metastasis, and apoptosis (Scagliotti et al, 2008; Liu et al, 2012). Other common KRAS mutations in lung cancer are G12V and G12D In other cancers, such as pancreatic cancer and colorectal cancer, KRAS mutations are frequent. Forty-one discriminative genes for KRAS mutations were identified using two stage feature selection approach: (1) minimal Redundancy Maximal Relevance (mRMR) and (2) Incremental Feature Selection (IFS)

METHODS

RESULTS AND DISCUSSION

DATA AVAILABILITY STATEMENT