215P - Detection of MUTYH for the prognosis and chemotherapy responsiveness of patients with non-small cell lung cancer

Background

Lung cancer is the most prevalent cancer in Hong Kong and over 80% of the lung cancers are non-small cell lung cancer (NSCLC). Mutation of MUTYH has been suggested to be associated with a number of malignancies such as breast, colorectal, and bladder cancers. However, the role of MUTYH in NSCLC remains highly elusive. The objectives of the study are to investigate the functional role of MUTYH in NSCLC, to correlate the expression of MUTYH with the prognosis of NSCLC patients, and to correlate the gene expression of MUTYH with the chemotherapy responsiveness of NSCLC patients.

Methods

Plasmid transfection of MUTYH by Lipofectamine method was performed to generate cell lines with MUTYH overexpression. Gene and protein expression levels were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting respectively. Apoptosis by Annexin V assay was carried out to examine the effect of cisplatin on MUTYH-overexpressing cells while trans-well invasion and migration assays were done to investigate their invasive and migratory ability. Immunohistochemistry was performed to examine the protein expression level of MUTYH in NSCLC tissue samples whereas RT-qPCR was performed to determine the gene expression level of MUTYH in both tissue and blood samples.

Results

MUTYH-overexpressing cancer cells demonstrated reduced invasive and migratory ability but a higher apoptotic percentage, indicating higher expression of MUTYH would lower the capacity of cancer cells to escape from primary tumours and invade adjacent tissues leading to metastases but promote the occurrence of programmed cell death. Moreover, higher expression of MUTYH conferred better prognosis but no correlation with treatment prediction as Kaplan Meier analysis revealed a significantly longer median overall survival and relapse-free survival in the high-expression group of MUTYH than the low-expression one.

Conclusions

This study identified MUTYH as a potential prognostic marker of NSCLC and the findings of this study may provide more precise prognostication of NSCLC and thus better clinical management of lung cancer for patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Queen Elizabeth Hospital.

Funding

The project was supported by the Health and Medical Research Fund (project reference number: 07180176), the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region.

Disclosure

All authors have declared no conflicts of interest.