A team of researchers has found that the expression pattern of certain microRNAs (miRNAs) may predict tumor aggressiveness in some patients with lung cancer. These findings indicate that miRNAs may represent a new class of diagnostic and prognostic tools for lung cancer, according to study results in the March 13 Cancer Cell.

miRNAs are small segments of RNA thought to control gene expression. Their actions could change the expression of cancer-related genes within a cell and lead to malignancies.

The researchers identified two miRNAs - has-mir-155 and has-let-7a-2 - that could be used as prognostic indicators in patients with adenocarcinoma of the lung. High levels of has-mir-155 or low levels of has-let-7a-2 were associated with poor prognosis. Specifically, overexpression of has-mir-155 was the most significant indicator of this prognosis, independent of tumor stage. Although these miRNAs have been identified in other cancers, this is the first evidence linking has-mir-155 to lung cancer.

A tumor with an overexpression of has-mir-155 or reduced expression of has-let-7a-2 would indicate the need for aggressive chemotherapy or radiation treatments. Other tumors that do not show high has-mir-155 or low has-let-7a-2 levels are less aggressive, and those patients might not require more therapy.

"This study is significant because it provides another tool for studying prognosis that is independent of tumor stage," said Dr. Curtis Harris, chief of the Laboratory of Human Carcinogenesis in NCI's Center for Cancer Research (CCR) and co-leader of this study. "Following surgery, 50 to 60 percent of patients with stage I lung cancer will develop metastatic disease within 5 years. This may indicate that there are micrometastases that have not been detected by imaging, scanning, or pathology.

"In the future, we can use miRNAs and other biological predictors to select patients who may need more aggressive treatment versus those who may not," Dr. Harris continued. "Additional studies confirming these results are the next step before incorporating miRNA analysis into routine clinical practice."

The study was a collaboration among researchers at Ohio State University Comprehensive Cancer Center, Jikei University School of Medicine in Tokyo, the National Cancer Center Research Institute in Tokyo, and NCI's CCR.

The researchers examined 104 pairs of primary tumor tissues and corresponding noncancerous lung tissues. Each tissue pair was obtained from the same patient to eliminate genetic differences between tumor and normal tissues.

Patterns of miRNA expression in each tumor and normal tissue pair were studied by microarray analysis. Five miRNAs displayed different expression levels in tumor tissues versus their controls and were selected for further study. Statistical analysis 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.

By Lynette Grouse