1.Genetic features associated with ¹⁸F-FDG uptake in intrahepatic cholangiocarcinoma
Keun Soo AHN ; Koo Jeong KANG ; Yong Hoon KIM ; Tae Seok KIM ; Bong Il SONG ; Hae Won KIM ; Daniel O'BRIEN ; Lewis R ROBERTS ; Jeong Woo LEE ; Kyoung Sook WON
Annals of Surgical Treatment and Research 2019;96(4):153-161
PURPOSE: In intrahepatic cholangiocarcinoma (iCCA), genetic characteristics on ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG)-PET scans are not yet clarified. If specific genetic characteristics were found to be related to FDG uptake in iCCA, we can predict molecular features based on the FDG uptake patterns and to distinguish different types of treatments. In this purpose, we analyzed RNA sequencing in iCCA patients to evaluate gene expression signatures associated with FDG uptake patterns. METHODS: We performed RNA sequencing of 22 cases iCCA who underwent preoperative ¹⁸F-FDG-PET, and analyzed the clinical and molecular features according to the maximum standard uptake value (SUVmax). Genes and biological pathway which are associated with SUVmax were analyzed. RESULTS: Patients with SUVmax higher than 9.0 (n = 9) had poorer disease-free survival than those with lower SUVmax (n = 13, P = 0.035). Genes related to glycolysis and gluconeogenesis, phosphorylation and cell cycle were significantly correlated with SUVmax (r ≥ 0.5). RRM2, which is related to the toxicity of Gemcitabine was positively correlated with SUVmax, and SLC27A2 which is associated with Cisplastin response was negatively correlated with SUVmax. According to the pathway analysis, cell cycle, cell division, hypoxia, inflammatory, and metabolism-related pathways were enriched in high SUVmax patients. CONCLUSION: The genomic features of gene expression and pathways can be predicted by FDG uptake features in iCCA. Patients with high FDG uptake have enriched cell cycle, metabolism and hypoxic pathways, which may lead to a more rational targeted treatment approach.
Anoxia
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Cell Cycle
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Cell Division
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Cholangiocarcinoma
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Disease-Free Survival
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Fluorodeoxyglucose F18
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Gene Expression
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Gluconeogenesis
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Glycolysis
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Humans
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Metabolism
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Phosphorylation
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Positron-Emission Tomography
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Sequence Analysis, RNA
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Transcriptome
2.Identification of new genetic risk factors for prostate cancer.
Michelle GUY ; Zsofia KOTE-JARAI ; Graham G GILES ; Ali Amin Al OLAMA ; Sarah K JUGURNAUTH ; Shani MULHOLLAND ; Daniel A LEONGAMORNLERT ; Stephen M EDWARDS ; Jonathan MORRISON ; Helen I FIELD ; Melissa C SOUTHEY ; Gianluca SEVERI ; Jenny L DONOVAN ; Freddie C HAMDY ; David P DEARNALEY ; Kenneth R MUIR ; Charmaine SMITH ; Melisa BAGNATO ; Audrey T ARDERN-JONES ; Amanda L HALL ; Lynne T O'BRIEN ; Beatrice N GEHR-SWAIN ; Rosemary A WILKINSON ; Angela COX ; Sarah LEWIS ; Paul M BROWN ; Sameer G JHAVAR ; Malgorzata TYMRAKIEWICZ ; Artitaya LOPHATANANON ; Sarah L BRYANT ; null ; null ; null ; Alan HORWICH ; Robert A HUDDART ; Vincent S KHOO ; Christopher C PARKER ; Christopher J WOODHOUSE ; Alan THOMPSON ; Tim CHRISTMAS ; Chris OGDEN ; Cyril FISHER ; Charles JAMESON ; Colin S COOPER ; Dallas R ENGLISH ; John L HOPPER ; David E NEAL ; Douglas F EASTON ; Rosalind A EELES
Asian Journal of Andrology 2009;11(1):49-55
There is evidence that a substantial part of genetic predisposition to prostate cancer (PCa) may be due to lower penetrance genes which are found by genome-wide association studies. We have recently conducted such a study and seven new regions of the genome linked to PCa risk have been identified. Three of these loci contain candidate susceptibility genes: MSMB, LMTK2 and KLK2/3. The MSMB and KLK2/3 genes may be useful for PCa screening, and the LMTK2 gene might provide a potential therapeutic target. Together with results from other groups, there are now 23 germline genetic variants which have been reported. These results have the potential to be developed into a genetic test. However, we consider that marketing of tests to the public is premature, as PCa risk can not be evaluated fully at this stage and the appropriate screening protocols need to be developed. Follow-up validation studies, as well as studies to explore the psychological implications of genetic profile testing, will be vital prior to roll out into healthcare.
Genetic Predisposition to Disease
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genetics
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Genetic Testing
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Humans
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Kallikreins
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genetics
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Male
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Membrane Proteins
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genetics
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Prostatic Neoplasms
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diagnosis
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genetics
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Prostatic Secretory Proteins
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genetics
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Protein-Serine-Threonine Kinases
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genetics
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Risk Factors