Lack of Olig1 protein in lung tumors may increase risk of death

Apr 2 2007

A study of human lung tumors indicates that lung cancer patients who lack a particular protein may do more poorly than those with normal levels of that same protein.

If the findings are verified in a clinical trial, the absence of the protein might be used to identify lung cancer patients who need more aggressive therapy after surgery.

The protein is the product of a gene called Olig1, which previously has not been linked with lung cancer, and it is located in a chromosome region that is often lost in the tumor cells of many lung-cancer patients.

The research examined tumors from people with non-small cell lung cancer (NSCLC), the most common form of lung cancer. It sought to identify genes that are turned off, or silenced, by a process called aberrant DNA methylation.

The study wanted to learn if the pattern of silenced genes could distinguish between two subtypes of NSCLC, adenocarcinoma and squamous cell carcinoma.

The research identified 47 genes that together can differentiate between the two lung cancer subtypes. It also found that the silencing of the Olig1 gene, which results in the absence or low levels of its protein product, was linked to poor survival in NSCLC patients.

The study, led by researchers at the Ohio State University Comprehensive Cancer Center, is published in the March 27 issue of PLoS Medicine.

"We found that when the Olig1 protein is down-regulated or absent, the risk of death is significantly higher compared with patients who have normal levels of the protein," says first-author Romulo M. Brena, a graduate research associate in molecular genetics and in molecular virology, immunology and medical genetics.

"Even low levels of the protein were associated with better survival," he says.

The findings might have important clinical significance, says coauthor Gregory Otterson, associate professor of internal medicine and a medical oncologist who specializes in lung cancer treatment.

"This study identified a novel gene that had no known role in lung cancer development and that is silenced in a large number of patients," says Otterson, also a researcher with the Ohio State University Comprehensive Cancer Center . "The absence of the protein may have important prognostic implications."

Lung cancer is the leading cause of cancer illness and death worldwide. Every year, an estimated 1.2 million people are diagnosed with the malignancy, and 1.1 million others die from the disease. More than 85 percent of these cases are NSCLC.

Presently, a lung-cancer patient's prognosis is based on how far the disease has progressed, which is determined by staging the disease.

"There is a high correlation between survival and a patient's stage," Brena says. "But there is also wide variation in overall survival among patients who are in the same stage. Some live for only a short time, others for a longer time.

"We don't know why that is, but it is probably related to the molecular and genetic characteristics of the tumor," he says. "The presence or absence of Olig1 may be one of those characteristics."

An analysis of patient survival data indicated that patients with little or no Olig1 in their tumor cells had about a 15 percent decrease in survival.

The researchers are now trying to learn the role of the Olig1 gene and protein in lung cells and how their loss may contribute to cancer development.

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