KRAS mutation and protein levels in gastric cancer patients and response to MEK inhibitors

Background

Recent studies have suggested that KRAS plays an important role in gastric cancer. The aim of this study was to assess the prognostic effect of KRAS mutation and expression levels in gastric cancer patients and to explore its potential role in targeted therapy.

Methods

We examined KRAS protein levels in 132 stage I-IV gastric cancer using immunochemistry. KRAS mutation was detected by next generation exome sequencing. KRAS mutation was examined in five human gastric cell lines (AGS, SNU601, SNU668, KATO-III and NUGC-4) by Sanger sequencing. Cytosensitivity of MEK inhibitors (AZD6244) in the five cell lines was examined by MTT.

Results

The median age of the total number of 132 gastric cancer patients was 58 years (range: 30-82). There were 75 gastric cancer samples with the pathology of signet-ring cell carcinoma (SRCC), while another 57 samples with adenocarcinoma. 80% of gastric SRCC samples have high expression of KRAS protein compared with 34.69% of gastric adenocarcinomas (P 

Conclusions

KRAS is highly expressed in SRCC. Patients with KRAS mutations have shorter OS. Gastric SRCC cell lines with KRAS mutation are sensitive to MEK inhibitor (AZD6244). The results provide insights into the important role of mutant KRAS in the prognosis and response to MEK inhibitor of gastric SRCC patients.

Clinical trial identification

none

Legal entity responsible for the study

Jia Wei

Funding

Nation Science Foundation

Disclosure

All authors have declared no conflicts of interest.