One reason why lung cancer is one of the deadliest forms of cancer in the United States is that it is so difficult to detect at its earliest stages, when treatment is most effective. Unlike breast or skin cancer, there are no telltale lumps or spots to provide physicians an early sign in at-risk patients. Likewise, there are no routine diagnostic procedures, such as mammograms or colonoscopies, that can reliably spot cancer in the lungs.
But what if a simple blood test—no more invasive than having your cholesterol or blood sugar levels checked—could do the trick?
A recent study from The Wistar Institute confirms the effectiveness of detecting lung cancer by taking a snapshot of gene activity in blood-borne immune cells. According to the researchers, their efforts could lead to a simple blood test that could detect non-small cell lung cancer (NSCLC) at an early stage—when surgery is most effective—and also determine if any signs of the cancer remain following surgery.
“It has long been known that cancers interact with the immune system. Genomics technology has gotten to the point where we can see the effect cancer has on individual cells in that immune system,” said Louise C. Showe, Ph.D., a professor in Wistar’s Immunology and Molecular & Cellular Oncology programs and director of Wistar’s genomics facility. “With a simple blood draw, we can detect lung cancer, show the effectiveness of cancer surgery, by sampling the same patient’s blood for analysis after surgery and hopefully even determine if the cancer may return. We also show in this study that the expression patterns in the blood of small regulatory RNA molecules called microRNAs are also affected by the presence of the tumor and are also likely to have diagnostic potential.”
Their work follows up on a study the Showe lab published in 2009, which demonstrated the correlation between the presence of NSCLC and gene expression patterns—changes in gene activity—within peripheral mononuclear blood cells (PBCs), white blood cells like leukocytes and lymphocytes. The present study took the research further to show that such gene expression patterns change after tumor removal and in many cases could return to normal in patients following successful surgery. They also found a panel of genes that could distinguish between malignant tumors and non-malignant lung nodules, suggesting that such a blood test could also guide treatment decisions and help prevent unnecessary surgeries involving non-malignant lung nodules.
“It has become clear to us that we are on the correct path, and we are working to further validate and expand our findings by studying more patient samples so that we have enough evidence to take this concept into clinical trials,” Showe said.
Lung cancer has proven to be the deadliest cancer worldwide and, in the United States, accounted for over 158,000 deaths in 2010, according to the latest American Cancer Society statistics. Detecting the cancer early and surgically removing it is, at present, the most effective treatment for NSCLC, which accounts for 75 percent of lung tumors. Survival rates dramatically decline in later stages, as tumors metastasize, or spread, throughout the body.
“In the past, tests that offer a chance to detect cancer early, such as clonoscopies and mammograms, have dramatically affected breast and colon cancer survival rates,” Showe said. “Similarly, we believe that if we could create at routine and effective blood test to monitor the large numbers of people at-risk for lung cancer, that could save the many lives.”
Through a collaboration with doctors at the University of Pennsylvania School of Medicine and the New York University School of Medicine, the Wistar scientists tested blood samples taken from 18 patients just prior to surgery and again one to five months later. According to Showe, the changes are clearly related to the tumor’s absence and not the surgery itself, as they compared their results to samples taken from patients who had lung surgery for a smoking-related nonmalignant lung disease as well. In fact, the researchers found that removing the tumor changed the expression of a large number of protein-coding genes within the immune cells but only 50 of these genes were required to separate cancers from non-cancers.
Showe and her team, however, were also interested in understanding how the expression levels—a determination of how frequently a given gene is read or “expressed”—of these genes within PBMCs paint a picture of how cancer cells impact the immune system. “The immune system, in a sense, sees and reacts to the cancer, even if it cannot always successfully intervene,” Showe said.
From their panel of important genes, the researchers looked for relative amounts of messenger RNA (mRNA), the written transcript of a gene used for the production of proteins, and micro RNA (miRNA), short stretches of gene transcripts that have a regulatory function on their own. The researchers found that alterations in the expression of just five miRNAs could determine the presence or absence of lung cancer. The smaller the panel, the less expensive and more practical a blood test becomes, Showe says. This multi-pronged approach to understanding how the cancer and immune cells interact, and combining the different types of information may provide more robust ways of detecting early stage lung cancers.
“Genomics technology, the ability to detect and determine gene activity, has dramatically improved in just the last decade, and so have the costs associated with scanning for gene activity,” Showe said. “We are continuing to improve sample collection techniques, determine the most precise gene expression patterns, and refine a viable clinical blood test for lung cancer from this process.”
The Showe laboratory continues collecting patient samples through its collaborators at Penn and NYU and, soon, through Wistar's recent partnership with the Helen F. Graham Cancer Center at Christiana Care in Delaware.
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Partnership with Christiana Care