{"470491":{"#nid":"470491","#data":{"type":"news","title":"Metabolic Profiles Distinguish Early Stage Ovarian Cancer with Unprecedented Accuracy","body":[{"value":"\u003Cp\u003EStudying blood serum compounds of different molecular weights has led scientists to a set of biomarkers that may enable development of a highly accurate screening test for early-stage ovarian cancer.\u003C\/p\u003E\u003Cp\u003EUsing advanced liquid chromatography and mass spectrometry techniques coupled with machine learning computer algorithms, researchers have identified 16 metabolite compounds that provided unprecedented accuracy in distinguishing 46 women with early-stage ovarian cancer from a control group of 49 women who did not have the disease. Blood samples for the study were collected from a broad geographic area \u2013 Canada, Philadelphia and Atlanta.\u003C\/p\u003E\u003Cp\u003EWhile the set of biomarkers reported in this study are the most accurate reported thus far for early-stage ovarian cancer, more extensive testing across a larger population will be needed to determine if the high diagnostic accuracy will be maintained across a larger group of women representing a diversity of ethnic and racial groups.\u003C\/p\u003E\u003Cp\u003EThe research was reported November 17 in the journal \u003Cem\u003EScientific Reports\u003C\/em\u003E, an open access journal from the publishers of \u003Cem\u003ENature\u003C\/em\u003E.\u003C\/p\u003E\u003Cp\u003E\u201cThis work provides a proof of concept that using an integrated approach combining analytical chemistry and learning algorithms may be a way to identify optimal diagnostic features,\u201d said \u003Ca href=\u0022http:\/\/www.biology.gatech.edu\/people\/john-mcdonald\u0022\u003EJohn McDonald\u003C\/a\u003E, a professor in the \u003Ca href=\u0022http:\/\/www.biology.gatech.edu\/\u0022\u003ESchool of Biolog\u003C\/a\u003Ey at the Georgia Institute of Technology and director of its Integrated Cancer Research Center. \u201cWe think our results show great promise and we plan to further validate our findings across much larger samples.\u201d\u003C\/p\u003E\u003Cp\u003EOvarian cancer has been difficult to treat because it typically is not diagnosed until after it has metastasized to other areas of the body. Researchers have been seeking a routine screening test that could diagnose the disease in stage one or stage two \u2013 when the cancer is confined to the ovaries.\u003C\/p\u003E\u003Cp\u003EWorking with three cancer treatment centers in the U.S. and Canada, the Georgia Tech researchers obtained blood samples from women with stage one and stage two ovarian cancer. They separated out the serum, which contains proteins and metabolites \u2013 molecules produced by enzymatic reactions in the body.\u003C\/p\u003E\u003Cp\u003EThe serum samples were analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS), which is two instruments joined together to better separate samples into their individual components. Heavier molecules are separated from lighter molecules, and the molecular signatures are determined with enough accuracy to identify the specific compounds. The Georgia Tech researchers decided to look only at the metabolites in their research.\u003C\/p\u003E\u003Cp\u003E\u201cPeople have been looking at proteins for diagnosis of ovarian cancer for a couple of decades, and the results have not been very impressive,\u201d said \u003Ca href=\u0022http:\/\/www.chemistry.gatech.edu\/people\/Fernandez\/Facundo%20M.\u0022\u003EFacundo Fern\u00e1ndez\u003C\/a\u003E, a professor in Georgia Tech\u2019s \u003Ca href=\u0022http:\/\/www.chemistry.gatech.edu\/\u0022\u003ESchool of Chemistry and Biochemistry\u003C\/a\u003E who led the analytical chemistry part of the research. \u201cWe decided to look in a different place for molecules that could potentially provide diagnostic capabilities. It\u2019s one of the places that people had really not studied before.\u201d\u003C\/p\u003E\u003Cp\u003ESamples from each of the 46 cancer patients were divided so they could be analyzed in duplicate. The researchers also looked at serum samples from 49 women who did not have cancer. The work required eliminating unrelated compounds such as caffeine, and molecules that were not present in all the cancer patients.\u003C\/p\u003E\u003Cp\u003E\u201cWe used really high resolution equipment and instrumentation to be able to separate most of the components of the samples,\u201d Fern\u00e1ndez explained. \u201cOtherwise, detection of early-stage ovarian cancer is very difficult because you have a lot of confounding factors.\u201d\u003C\/p\u003E\u003Cp\u003EThe chemical work identified about a thousand candidate compounds. That number was reduced to about 255 through the work of research scientist David Gaul, who removed duplicates and unrelated molecules from the collection.\u003C\/p\u003E\u003Cp\u003EThese 255 compounds were then analyzed by a learning algorithm which evaluated the predictive value of each one. Molecules that did not contribute to the predictive accuracy of the screening were eliminated. Ultimately, the algorithm produced a list of 16 molecules that together differentiated cancer patients with extremely high accuracy \u2013 greater than 90 percent.\u003C\/p\u003E\u003Cp\u003E\u201cThe algorithm looks at the metabolic features and correlates them with whether the samples were from cancer or control patients,\u201d McDonald explained. \u201cThe algorithm has no idea what these compounds are. It is simply looking for the combination of molecules that provides the optimal predictive accuracy. What is encouraging is that many of the diagnostic features identified are metabolites that have been previously implicated in ovarian cancer.\u201d\u003C\/p\u003E\u003Cp\u003EAs a next step, McDonald and Fern\u00e1ndez would like to study samples from a larger population that includes significant numbers of different ethnic and racial groups. Those individuals may have different metabolites that could serve as biomarkers for ovarian cancer.\u003C\/p\u003E\u003Cp\u003EThough sophisticated laboratory equipment was required to identify the 16 molecules, a screening test would not require the same level of sophistication, Fern\u00e1ndez said.\u003C\/p\u003E\u003Cp\u003E\u201cOnce you know what these molecules are, the next step would be to set up a clinical assay,\u201d he said. \u201cMass spectrometry is a common tool in this field. We could use a clinical mass spectrometer to look at only the molecules we are interested in. Moving this to a clinical assay would take work, but I don\u2019t see any technical barriers to doing it.\u201d\u003C\/p\u003E\u003Cp\u003EThe Fern\u00e1ndez and McDonald groups have used a similar approach with prostate cancer and plan to explore its utility for detecting other types of cancer.\u003C\/p\u003E\u003Cp\u003E\u003Cem\u003EThe research was supported by grants from The Laura Crandall Brown Ovarian Cancer Foundation, The Ovarian Cancer Research Fund, The Ovarian Cancer Institute, Northside Hospital (Atlanta), The Robinson Family Fund, and the Deborah Nash Endowment Fund.\u003C\/em\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ECITATION\u003C\/strong\u003E: David A. Gaul, et al., \u201cHighly-accurate metabolomics detection of early-stage ovarian cancer,\u201d (Scientific Reports, 2015). \u003Ca href=\u0022http:\/\/www.dx.doi.org\/10.1038\/srep16351\u0022 title=\u0022http:\/\/www.dx.doi.org\/10.1038\/srep16351\u0022\u003Ehttp:\/\/www.dx.doi.org\/10.1038\/srep16351\u003C\/a\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EResearch News\u003C\/strong\u003E\u003Cbr \/\u003E\u003Cstrong\u003EGeorgia Institute of Technology\u003C\/strong\u003E\u003Cbr \/\u003E\u003Cstrong\u003E177 North Avenue\u003C\/strong\u003E\u003Cbr \/\u003E\u003Cstrong\u003EAtlanta, Georgia 30332-0181 USA\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EMedia Relations Contact\u003C\/strong\u003E: John Toon (\u003Ca href=\u0022mailto:jtoon@gatech.edu\u0022\u003Ejtoon@gatech.edu\u003C\/a\u003E) (404-894-6986).\u003Cbr \/\u003E\u003Cstrong\u003EWriter\u003C\/strong\u003E: John Toon\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003EStudying blood serum compounds of different molecular weights has led scientists to a set of biomarkers that may enable development of a highly accurate screening test for early-stage ovarian cancer.\u0026nbsp;\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"A new study has produced a set of biomarkers that may enable development of an accurate ovarian cancer screening test."}],"uid":"27303","created_gmt":"2015-11-17 10:48:08","changed_gmt":"2016-10-08 03:20:03","author":"John Toon","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2015-11-17T00:00:00-05:00","iso_date":"2015-11-17T00:00:00-05:00","tz":"America\/New_York"},"extras":[],"hg_media":{"470421":{"id":"470421","type":"image","title":"UPLC-MS analysis of samples","body":null,"created":"1449257160","gmt_created":"2015-12-04 19:26:00","changed":"1475895218","gmt_changed":"2016-10-08 02:53:38","alt":"UPLC-MS analysis of samples","file":{"fid":"203887","name":"ovarian-cancer001.jpg","image_path":"\/sites\/default\/files\/images\/ovarian-cancer001_0.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/ovarian-cancer001_0.jpg","mime":"image\/jpeg","size":1337488,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/ovarian-cancer001_0.jpg?itok=tn0wvRpL"}},"470431":{"id":"470431","type":"image","title":"UPLC-MS analysis of samples2","body":null,"created":"1449257160","gmt_created":"2015-12-04 19:26:00","changed":"1475895220","gmt_changed":"2016-10-08 02:53:40","alt":"UPLC-MS analysis of samples2","file":{"fid":"203888","name":"ovarian-cancer004.jpg","image_path":"\/sites\/default\/files\/images\/ovarian-cancer004_1.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/ovarian-cancer004_1.jpg","mime":"image\/jpeg","size":1003858,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/ovarian-cancer004_1.jpg?itok=nXvrOqJq"}},"470461":{"id":"470461","type":"image","title":"UPLC-MS analysis of samples3","body":null,"created":"1449257176","gmt_created":"2015-12-04 19:26:16","changed":"1475895220","gmt_changed":"2016-10-08 02:53:40","alt":"UPLC-MS analysis of samples3","file":{"fid":"203890","name":"ovarian-cancer006.jpg","image_path":"\/sites\/default\/files\/images\/ovarian-cancer006_0.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/ovarian-cancer006_0.jpg","mime":"image\/jpeg","size":1232375,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/ovarian-cancer006_0.jpg?itok=sWO_eP10"}},"470481":{"id":"470481","type":"image","title":"UPLC-MS analysis of samples4","body":null,"created":"1449257176","gmt_created":"2015-12-04 19:26:16","changed":"1475895220","gmt_changed":"2016-10-08 02:53:40","alt":"UPLC-MS analysis of samples4","file":{"fid":"203892","name":"ovarian-cancer007.jpg","image_path":"\/sites\/default\/files\/images\/ovarian-cancer007_0.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/ovarian-cancer007_0.jpg","mime":"image\/jpeg","size":1478703,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/ovarian-cancer007_0.jpg?itok=rLw-SJTE"}}},"media_ids":["470421","470431","470461","470481"],"groups":[{"id":"1188","name":"Research Horizons"}],"categories":[{"id":"140","name":"Cancer Research"},{"id":"146","name":"Life Sciences and Biology"},{"id":"135","name":"Research"}],"keywords":[{"id":"7579","name":"biomarkers"},{"id":"385","name":"cancer"},{"id":"17301","name":"Facundo Fernandez"},{"id":"2371","name":"John McDonald"},{"id":"2372","name":"ovarian cancer"},{"id":"171503","name":"screening test"}],"core_research_areas":[{"id":"39441","name":"Bioengineering and Bioscience"}],"news_room_topics":[{"id":"71891","name":"Health and Medicine"}],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003EJohn Toon\u003C\/p\u003E\u003Cp\u003EResearch News\u003C\/p\u003E\u003Cp\u003E\u003Ca href=\u0022mailto:jtoon@gatech.edu\u0022\u003Ejtoon@gatech.edu\u003C\/a\u003E\u003C\/p\u003E\u003Cp\u003E(404) 894-6986\u003C\/p\u003E","format":"limited_html"}],"email":["jtoon@gatech.edu"],"slides":[],"orientation":[],"userdata":""}},"428651":{"#nid":"428651","#data":{"type":"news","title":"Cancer may not be caused by mutations alone","body":[{"value":"\u003Cp class=\u0022p1\u0022\u003EThere are more than 200 diseases called cancer and they all start when abnormal cells in a part of the body divide uncontrollably, growing with reckless abandon. Why these bad cells run amok is the focus of thousands of researchers across the world and billions of dollars.\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EThe current consensus among the vast majority of researchers is that most if not all cancers are caused by a change in or damage to genes, collectively called \u201cmutations.\u201d But research from two Georgia Institute of Technology cancer geneticists may alter the prevailing view.\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u201cWith the exception of the few things that we know are related to predisposition, the consensus view now is that cancer is due to \u2018de novo\u2019 mutations,\u201d says John McDonald, professor of Biology and director of the Integrated Cancer Research Center (ICRC) at the Petit Institute for Bioengineering and Bioscience.\u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EThe term \u201cmutation\u201d is typically used to encompass a broad spectrum on genomic level lesions ranging from small changes in the single letter DNA code (point mutations) to large chromosomal deletions and rearrangements (structural mutations) that can adversely affect the architecture and function of cells.\u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EThe explosion in the number of genome sequencing studies carried out over the past several years comparing normal and cancer tissues has generated an abundance of genome databases ripe for computational analyses of the spectrum of mutations associated with cancer. \u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EIn a study just reported in the online journal \u003Cem\u003E\u003Ca href=\u0022http:\/\/www.biomedcentral.com\/1755-8794\/8\/40\u0022\u003EBMC Medical Genomics \u003C\/a\u003E\u0026nbsp;\u003C\/em\u003EMcDonald and Vinay Mittal (former graduate student in McDonald\u2019s lab, now a bioinformatics scientist with Thermo Fisher Scientific in Michigan) report the results of a detailed analysis of structural mutations associated with ovarian cancer \u2013 the deadliest of all gynecological cancers.\u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EUnlike most computational analyses of cancer mutations, the authors not only analyzed the structural variants found in cancer tissues but also those naturally occurring mutations present in the normal tissues of the same patients.\u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u201cThe results were remarkable in the shear number of structural mutations identified,\u201d says McDonald. They found 4,516 structural mutations in the cancer tissues and 5,518 in the normal tissues.\u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u201cMost of the structural variants identified are probably of little functional significance,\u201d says Mittal. \u201cBut around 10 percent of the variants identified are \u2018gene-fusions\u2019 with the potential to generate hybrid proteins that may contribute significantly to cancer onset and progression.\u201d\u003C\/p\u003E\u003Ch6 class=\u0022p1\u0022\u003E\u003Cstrong\u003EDisease of Misinformation\u003C\/strong\u003E\u003C\/h6\u003E\u003Cp class=\u0022p1\u0022\u003EIn addition to identifying and categorizing all of the structural variants associated with the ovarian cancer patients, Mittal and McDonald went on to determine the extent to which these variants were actually being expressed in the normal and cancer tissues.\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EWhile our DNA harbors all of the genetic information in our cells, like a blueprint, not all of this information is transmitted or \u201cexpressed\u201d at any given time.\u0026nbsp; Information in DNA must be transmitted to an intermediary RNA molecule before it can result in the manufacture of a functional protein. For example, many of the genes necessary for liver cell function are not expressed in the brain, and vice versa.\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EThe detailed pattern of regulatory controls typical in normal cells is often disrupted in cancer cells. Thus, cancer cells not only contain DNA lesions or mutations not detected in normal cells, they may also display abnormal expression patterns, \u201cgenetic information that is silenced in normal cells but abnormally expressed in cancer cells,\u201d says McDonald, who has called cancer, \u201ca disease of misinformation.\u201d\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003ECells get wrong information, such as being told to rapidly divide when they should be inactive. It could be an error in the cell\u2019s blueprint (a mutation). Or, it could be an error in the flow of information (abnormal expression), a regulation problem, which gets to what may be the most remarkable and unexpected finding of the study, according to McDonald.\u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u201cAt least some of the functionally significant abnormal gene-fusions expressed in the cancer tissues are also present in normal tissues,\u201d he says. \u201cBut they are not being expressed.\u201d\u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EThe results of the study underscore the importance of gene regulation in cancer. It raises questions about how and when cancer is due to a de novo mutational event or a mistake in information flow.\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u201cThe accumulation of structural variants and other mutations in our cells with the potential to cause cancer may be inevitable as we age, but our cells may naturally strive to suppress the expression of some of this misinformation,\u201d says McDonald. \u201cThis suggests that while mutations may be necessary for the onset of most cancers, they my not be sufficient. We need to better understand the regulatory mechanisms that can suppress cancer causing mutations in some individuals and how these mechanisms break down in cancer patients.\u201d\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EStudies are currently on-going to see if the suppression of cancer causing genetic lesions extends to other classes of mutation and to understand the molecular processes that may underlie the suppression mechanism. The hope is that this work will lead to novel and more effective therapies and treatments for cancer.\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u003Cem\u003EThe Parker H. Petit Institute for Bioengineering and Bioscience, an internationally recognized hub of multidisciplinary research at the Georgia Institute of Technology, brings engineers, scientists, and clinicians together to solve some of the world\u2019s most complex health challenges. With 17 research centers, more than 170 faculty members, and $24 million in state-of-the-art facilities, the Petit Institute is translating scientific discoveries into game-changing solutions to solve real-world problems.\u003C\/em\u003E\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u003Cstrong\u003E\u003Cbr \/\u003E\u003C\/strong\u003E\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u003Cstrong\u003ECONTACT:\u003C\/strong\u003E\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u003Cstrong\u003E\u003Ca href=\u0022http:\/\/hg.gatech.edu\/node\/jerry.grillo@ibb.gatech.edu\u0022\u003EJerry Grillo\u003C\/a\u003E\u003C\/strong\u003E\u003Cbr \/\u003ECommunications Officer II\u003Cbr \/\u003EParker H. Petit Institute for\u003Cbr \/\u003EBioengineering and Bioscience\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":[{"value":"New research by Georgia Tech scientists underscores importance of gene regulation"}],"field_summary":[{"value":"\u003Cp class=\u0022p1\u0022\u003E\u003Cstrong\u003ENew research by Georgia Tech scientists underscores importance of gene regulation\u0026nbsp;\u003C\/strong\u003E\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"New research by Georgia Tech scientists underscores importance of gene regulation"}],"uid":"28153","created_gmt":"2015-07-27 14:38:16","changed_gmt":"2016-10-08 03:19:15","author":"Jerry Grillo","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2015-07-27T00:00:00-04:00","iso_date":"2015-07-27T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"337561":{"id":"337561","type":"image","title":"John McDonald","body":null,"created":"1449245216","gmt_created":"2015-12-04 16:06:56","changed":"1475895051","gmt_changed":"2016-10-08 02:50:51","alt":"John McDonald","file":{"fid":"200556","name":"timthumb_3.jpeg","image_path":"\/sites\/default\/files\/images\/timthumb_3_0.jpeg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/timthumb_3_0.jpeg","mime":"image\/jpeg","size":71197,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/timthumb_3_0.jpeg?itok=QVvOiO_g"}}},"media_ids":["337561"],"groups":[{"id":"1292","name":"Parker H. Petit Institute for Bioengineering and Bioscience (IBB)"}],"categories":[],"keywords":[{"id":"280","name":"Cancer research"}],"core_research_areas":[{"id":"39441","name":"Bioengineering and Bioscience"}],"news_room_topics":[],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003E\u003Ca href=\u0022http:\/\/hg.gatech.edu\/node\/jerry.grillo@ibb.gatech.edu\u0022\u003EJerry Grillo\u003C\/a\u003E\u003Cbr \/\u003ECommunications Officer II\u003Cbr \/\u003EParker H. Petit Institute for\u003Cbr \/\u003EBioengineering and Bioscience\u003C\/p\u003E","format":"limited_html"}],"email":["jerry.grillo@ibb.gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}