Lung cancer is the leading cause of death due to cancer and is primarily caused by exposure to tobacco smoke. Scientists seek to better understand the mechanisms underlying this disease, and miRNAs may provide a way to examine the regulation of cancer-related genes.

"miRNAs are going to be important biomarkers of not only diagnosis and prognosis, but therapy, as well," said Harris. "The next step is to identify the genes that the miRNAs are affecting; they could be used as potential targets for developing novel therapies."


In the study, a total of 104 pairs of primary tumor tissues and corresponding noncancerous lung tissues were examined. The tumor and corresponding normal tissues were obtained from the same patient to eliminate genetic differences between tumor and normal tissues.

Researchers focused primarily on the more common adenocarcinomas in their analysis; adenocarcinomas and squamous cell carcinomas. Unlike adenocarcinomas, squamous cell carcinomas form in the cells lining the internal surfaces in the lung. These two tumor types are the most common lung cancers and are referred to as non-small cell lung cancers (NSCLC). In the study, adenocarcinomas of the lung comprised 63 percent of the tumors studied and squamous cell carcinomas comprised 37 percent.

Patterns of miRNA expression in each tumor and normal tissue pair were studied by microarray analysis. A microarray allows the measurement of hundreds of miRNAs simultaneously in a single sample. Five miRNAs displayed different expression levels in tumor tissues versus their corresponding noncancerous controls and, thus, were selected for further study. Upon statistical analysis, data showed that patients with high has-mir-155 or low has-let-7a-2 had poorer survival than patients showing low has-mir-155 or high has-let-7a-2 expression. The difference in the prognosis of these two groups was highly statistically significant.

After examining tissue from lung cancer patients, and following each patient to see how long they lived, researchers found that miRNA expression patterns were independent of tumor stage. When the scientists combined all clinical and molecular factors, they found that a high level of has-mir-155 or a low level of has-let-7a-2 was the most significant prognostic factor for an unfavorable patient outcome.

"This is promising research and is the first study to link these miRNAs to lung cancer," said Carlo Croce, M.D., chair of Molecular Virology, Immunology and Medical Genetics at The Ohio State University and study co-leader. "We are proposing that has-mir-155 may be acting like an oncogene in lung cancer." Oncogenes control cell growth and, when mutated, can contribute to abnormal cell growth. "miRNAs control the expression of a number of genes," noted Croce, "so if the miRNA is altered, this could lead to the alteration of a number of genes affecting malignant tumor growth. Although these results are encouraging, further testing is required to demonstrate the validity of using these markers for predicting patient outcomes."

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