The findings, published online December 1 in Cancer Research, a journal of the American Association for Cancer Research, could lead to a simple blood test to detect lung cancer in its earliest phases, when it can be most successfully treated.
Wistar investigators Louise C. Showe, Ph.D., and Michael K. Showe Ph.D., and colleagues examined gene expression profiles in blood samples from more than 200 patients with lung cancer or other, non-malignant, lung diseases. Focusing on non-small cell lung cancer (NSCLC), and the large at-risk population of smokers and ex-smokers, the researchers sought to determine whether lung tumors—even at the earliest stages—leave a gene expression signature in circulating blood cells. Recent studies have shown that in some late-stage cancers, an immune system response can be detected in the blood which can contain information on responsiveness to therapy or identify markers associated with prognosis.
For the study, peripheral blood was drawn from lung disease patients at the University of Pennsylvania Medical Center (Penn) and the New York University School of Medicine from 2003 through 2007, and the gene expression patterns in the samples were analyzed at Wistar. The team was able to identify a 29-gene “signature” that separated 137 patients with NSCLC tumors from 91 patient controls with non-malignant lung conditions, with 86 percent accuracy. Immune cells, which normally function to fight tumors, showed certain changes in the patients with malignant tumors that distinguished them from those of patients with other lung diseases such as chronic obstructive pulmonary disease or emphysema and patients with benign lung nodules.
When 18 NSCLC patients had peripheral blood drawn before surgery and again two to five months after their tumors were surgically removed, 13 of the samples showed a decrease in or complete disappearance of the tumor gene signature present in the pre-surgery samples after tumor removal. This finding demonstrates that the tumor presence can be communicated to the peripheral immune system and this signal can be detected in the gene expression patterns in peripheral blood.
Lung cancer is the most commonly occurring cancer in both men and women in the United States, accounting for 162,000 deaths in 2008, more than any other cancer. Early diagnosis followed by surgery presently is the most effective treatment for NSCLC, which accounts for 75 percent of lung tumors. Detecting cancer at its earliest stages would greatly improve the likelihood of survival; however, no simple and accurate screening test such as mammography for breast cancer or colonoscopy for colon cancer exists for lung cancer. In addition, early-stage lung cancers show few symptoms and tend to spread rapidly before they are found.
With further study, the findings may serve as the basis for developing a simpler screening test for lung cancer. “People routinely get blood taken at their doctor’s offices, for cholesterol levels, diabetes, and other standard tests, so why not utilize this method to screen for other conditions such as the risk of developing lung cancer?” says Louise Showe, a professor in Wistar’s Molecular and Cellular Oncology and Immunology programs and director of its genomics facility. “Such a test could be especially useful for remote areas where typically technologies that are used in urban centers are not available. In addition, this test could be useful in a clinical setting to help to decide whether a small tumor detected on an x-ray is likely to be malignant.”
The team is working to develop a simpler method for collecting and processing blood samples for analysis. In addition, the clinical collaborators are gathering follow-up data from patients which will be used to analyze the data for signatures of recurrence and/or response to therapy. The researchers are also conducting additional analyses to further explore the basis for the changes in the peripheral immune system after tumor removal.
The lead author on the Cancer Research publication is Michael K. Showe, Ph.D. Other researchers involved in the study from The Wistar Institute include Andrew V. Kossenkov, Ph.D.; Elena V. Nikonova, M.D.; Celia Chang, Ph.D.; Calen Nichols and David A. Speicher, Ph.D. Collaborators from the University of Pennsylvania School of Medicine include Steven M. Albelda, M.D.; Anil Vachani, M.D.; John Kucharczuk, M.D.; Bao Tran and Elliot Wakeam and from the New York University School of Medicine William N. Rom, M.D., M.P.H.; and Ting an Yie, M.S.
This study was support by Pennsylvania Department of Health (PA DOH) Tobacco Settlement Grants, the PA DOH Commonwealth Universal Research Enhancement Program, the National Cancer Institute, and a Wistar Cancer Center Support Grant.
The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the country, Wistar has long held the prestigious Cancer Center designation from the National Cancer Institute. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. The Wistar Institute: Today’s Discoveries – Tomorrow’s Cures. On the Web at www.wistar.org.
Michael K. Showe | Newswise Science News
Investigators may unlock mystery of how staph cells dodge the body's immune system
22.09.2017 | Cedars-Sinai Medical Center
Monitoring the heart's mitochondria to predict cardiac arrest?
21.09.2017 | Boston Children's Hospital
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
22.09.2017 | Life Sciences
22.09.2017 | Medical Engineering
22.09.2017 | Physics and Astronomy