Ability of miR-182 to predict outcome of patients with NSCLC

This study investigated the relationship between the protein miR-182 and outcome of patients with non small-cell lung cancer, including the development of tumor blood supply.

Non small-cell lung cancer (NSCLC) is the most common type of lung cancer (80-85% of lung cancer patients) and despite improvements in treatment options it has the lowest rate of survival. New drugs have been developed that target mutations (changes to DNA) in proteins associated with NSCLC. To improve diagnosis and treatment options biomarkers (distinguishing feature of disease) are being investigated to identify patients who may best benefit from these new targeted drugs.

One such biomarker being investigated is miR-182, a small protein. In NSCLC high levels of miR-182 are associated with advanced disease and poor patient outcome.

This investigation was based on data from a previous study which showed that out of 281 proteins only miR-182 was higher in patients with lung cancer when compared to healthy patients. 

This paper investigated the ability of miR-182 to predict patient outcome and its relationship with the formation of blood vessels that supply the tumor.

335 patients were chose to participate in the study. Patients were divided based on cancer type; 191 patients had squamous cell carcinomas (SCC; arising from flat cells that line the inside of the lungs), 113 adenocarcinomas (AC; arising from gland cells), and 31 large-cell carcinomas (LCC; appear as large round cells under the microscope). All patients underwent surgical procedures to remove the cancer. Protein levels were measured from tissue samples and compared to a control group of 20 patients. Disease-specific survival (time from surgery to death by cancer) was calculated and average time of follow-up was 105 months.

Overall patients with higher than normal levels of miR-182 were shown to have a better outcome; however the opposite was seen in patients diagnosed with large cell carcinoma.

Research has shown the role of miR-182 varies between cancer types acting to either suppress or promote the growth of the tumor. Results from this investigation showed that in NSCLC miR-182 acts in tumor suppression; particularly evident was the tumor suppressor activity of high miR-182 levels in patients with stage 2 or squamous cell NSCLC.

Females were shown to have a longer average time of progression-free survival (time without worsening of disease: 190 months) when compared to men (98 months). Furthermore female patients were shown to have a significantly higher 5-year survival rate (64%) in comparison to males (56%).

Results showed that high levels of miR-182 were shown to correspond to lower rates of tumor blood vessel formation.

Although miR-182 has been shown to have varied effects on tumor progression in various cancer types, this study demonstrated that in certain types of NSCLC high levels indicates improved patient outcome.

There was a large sex disparity between the study group with 76% of patients being male; more females will be required to validate the results.