A single gene may make the difference between surviving stomach cancer or not, according to a new study from the medical center. The research, published in the Dec. 10 issue of the journal Proceedings of the National Academy of Sciences, describes the discovery of a gene that produces less protein in the tumors of people who die early from the disease — information that could someday enhance diagnosis and treatment.

Samuel So, MD, associate professor of surgery at the School of Medicine and leader of the study, said the discovery of the gene’s role in gastric cancer could help researchers devise new treatments for the deadly disease. Stomach cancer ranks as the second-leading cause of cancer deaths worldwide and the 10th-leading cause of cancer deaths in the United States, especially in Asian populations. The chances of living five years after being diagnosed with stomach cancer is only 20 percent, So said.

In the study, So and his colleagues at Stanford and the University of Hong Kong searched for genes that make either more or less protein in stomach tumors than in surrounding stomach tissue. These genes, which have different expression patterns in tumors, have led to novel treatments in some cancers, such as the drug Herceptin for treating breast tumors that produce a particular protein.

The researchers first took tissue from 89 stomach tumors and extracted a molecule called mRNA from the cells. mRNA is produced by active genes and is eventually translated into a protein product — the more of a particular mRNA in a cell, the more protein is made.

They then attached a fluorescent molecule to the mRNA before washing it over the surface of a glass slide dotted with more than 30,000 genes. When the mRNA encountered its corresponding gene it stuck to the area, forming a glowing spot. The more mRNA from a particular gene, the brighter the spot appeared.

Upon comparing the pattern of spots between stomach tumor tissue and normal stomach tissue, So and his colleagues found a single spot that didn’t exist in normal tissue but was bright in the tumor tissue, indicating that the gene is turned on only in tumors. "When we looked at the data, the one gene stuck out like a sore thumb," said So, who is also director of Stanford’s Asian Liver Center.

The team then divided the tissue into those with high levels of the protein — called PLA2G2A — and those that made lower levels, comparing how long patients in the two groups survived.

It turns out that 60 percent of those who made large amounts of the protein survived five years, compared with 20 percent of those who made lower levels of the protein. "It seems to have a very predictive pattern," So added.

The question on researchers’ minds is what role the protein plays in preventing cancer. If they can work out its normal function, researchers could devise a way to either treat the cancer or better understand how it forms. Doctors could also test stomach tumors for PLA2G2A; patients with low expression would then be candidates for more aggressive treatment.

Although So and his team don’t fully understand the protein’s role in stomach cancer, past work shows that it acts as a first line of defense against bacteria in addition to being active in other types of cancers in both humans and mice. This could help explain one mystery in stomach cancer: The common stomach bacteria H. pylori has been implicated in causing stomach cancer, but 25 percent of those with stomach cancer have no signs of H. pylori infection. It could be that PLA2G2A helps fight infection from both H. pylori and an additional but still unknown cancer-causing bacteria, So said.

If the work results in a treatment or prevention strategy for the disease, it will greatly benefit the Asian population, which has the highest rate of stomach cancer. The disease ranks among the top five cancers in Asian populations in the San Francisco Bay area. For now, So said, the best strategy for treating gastric cancer is to catch it early.

So recommends people with stomach pain that isn’t relieved by over-the-counter remedies see their doctor for stomach cancer screening — particularly if the person is of Asian descent or has a family history of stomach cancer.