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Lipidomics and cancer

Xueheng Zhao, Marion G Brusadelli, Sharon L Sauter, Melinda Butsch Kovacic, Wujuan Zhang, Lindsey E Romick-Rosendale, Paul F Lambert, Kenneth D Setchell, Susanne I Wells
PURPOSE: Mutations in Fanconi anemia (FA) genes are common in sporadic squamous cell carcinoma of the head and neck (HNSCC) and we have previously demonstrated that FA pathway depletion in HNSCC cell lines stimulates invasion. The goal of our studies was to use a systems approach in order to define FA pathway-dependent lipid metabolism, and to extract lipid-based signatures and effectors of invasion in FA-deficient cells. EXPERIMENTAL DESIGN: We subjected FA-isogenic HNSCC keratinocyte cell lines to untargeted and targeted lipidomics analyses to discover novel biomarkers and candidate therapeutic targets in FA-deficient cells...
March 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Hui Ran, Yemin Zhu, Ruyuan Deng, Qi Zhang, Xisheng Liu, Ming Feng, Jie Zhong, Shuhai Lin, Xuemei Tong, Qing Su
BACKGROUND: Diabetic patients have a higher risk factor for colorectal cancer (CRC) metastasis. Stearoyl-CoA desaturase 1 (SCD1), the main enzyme responsible for producing monounsaturated fatty acids(MUFA) from saturated fatty acids, is frequently deregulated in both diabetes and CRC. The function and mechanism of SCD1 in metastasis of CRC and its relevance to glucose remains largely unknown. METHODS: SCD1 expression levels were analyzed in human CRC tissues and the Cancer Browser database ( https://genome-cancer...
March 12, 2018: Journal of Experimental & Clinical Cancer Research: CR
Xuan-Mei Piao, Young Joon Byun, Wun-Jae Kim, Jayoung Kim
Precision medicine is designed to tailor treatments for individual patients by factoring in each person's specific biology and mechanism of disease. This paradigm shifted from a "one size fits all" approach to "personalized and precision care" requires multiple layers of molecular profiling of biomarkers for accurate diagnosis and prediction of treatment responses. Intensive studies are also being performed to understand the complex and dynamic molecular profiles of bladder cancer. These efforts involve looking bladder cancer mechanism at the multiple levels of the genome, epigenome, transcriptome, proteome, lipidome, metabolome etc...
March 2018: Investigative and Clinical Urology
Ana C O Neves, Camilo L M Morais, Thais P P Mendes, Boniek G Vaz, Kássio M G Lima
Cervical cancer is still an important issue of public health since it is the fourth most frequent type of cancer in women worldwide. Much effort has been dedicated to combating this cancer, in particular by the early detection of cervical pre-cancerous lesions. For this purpose, this paper reports the use of mass spectrometry coupled with multivariate analysis as an untargeted lipidomic approach to classifying 76 blood plasma samples into negative for intraepithelial lesion or malignancy (NILM, n = 42) and squamous intraepithelial lesion (SIL, n = 34)...
March 2, 2018: Scientific Reports
Anna Wojakowska, Laura M Cole, Mykola Chekan, Katarzyna Bednarczyk, Magdalena Maksymiak, Małgorzata Oczko-Wojciechowska, Barbara Jarząb, Malcolm R Clench, Joanna Polańska, Monika Pietrowska, Piotr Widlak
INTRODUCTION: The distinction of papillary thyroid carcinomas from benign thyroid lesions has important implication for clinical man-agement. Classification based on histopathological features can be supported by molecular biomarkers, including lipidomic signatures, identified with the use of high-throughput mass spectrometry techniques. Formalin fixation is a standard procedure for stabilization and preservation of tissue samples, therefore this type of samples constitute highly valuable source of clinical material for retrospective molecular studies...
2018: Endokrynologia Polska
Elke Schaeffeler, Florian Büttner, Anna Reustle, Verena Klumpp, Stefan Winter, Steffen Rausch, Pascale Fisel, Jörg Hennenlotter, Stephan Kruck, Arnulf Stenzl, Judith Wahrheit, Denise Sonntag, Marcus Scharpf, Falko Fend, Abbas Agaimy, Arndt Hartmann, Jens Bedke, Matthias Schwab
BACKGROUND: Renal cell carcinoma (RCC) consists of prognostic distinct subtypes derived from different cells of origin (eg, clear cell RCC [ccRCC], papillary RCC [papRCC], and chromophobe RCC [chRCC]). ccRCC is characterized by lipid accumulation and metabolic alterations, whereas data on metabolic alterations in non-ccRCC are limited. OBJECTIVE: We assessed metabolic alterations and the lipid composition of RCC subtypes and ccRCC-derived metastases. Moreover, we elucidated the potential of metabolites/lipids for subtype classification and identification of therapeutic targets...
February 13, 2018: European Urology Focus
Mónica P Cala, Julian Aldana, Jessica Medina, Julián Sánchez, José Guio, Julien Wist, Roland J W Meesters
Breast cancer (BC) is a highly heterogeneous disease associated with metabolic reprogramming. The shifts in the metabolome caused by BC still lack data from Latin populations of Hispanic origin. In this pilot study, metabolomic and lipidomic approaches were performed to establish a plasma metabolic fingerprint of Colombian Hispanic women with BC. Data from 1H-NMR, GC-MS and LC-MS were combined and compared. Statistics showed discrimination between breast cancer and healthy subjects on all analytical platforms...
2018: PloS One
Mariona Jové, Irene Pradas, Alba Naudí, Susana Rovira-Llopis, Celia Bañuls, Milagros Rocha, Manuel Portero-Otin, Antonio Hernández-Mijares, Victor M Victor, Reinald Pamplona
Purpose: In this work, a non-targeted approach was used to unravel changes in the plasma lipidome of PCOS patients. The aim is to offer new insights in PCOS patients strictly selected in order to avoid confounding factors such as dyslipemia, obesity, altered glucose/insulin metabolism, cardiovascular disease, or cancer. Results: Multivariate statistics revealed a specific lipidomic signature for PCOS patients without associated pathologies. This signature implies changes, mainly by down-regulation, in glycerolipid, glycerophospholipid and sphingolipid metabolism suggesting an altered biosynthetic pathway of glycerophospholipids and cell signaling as second messengers in women with PCOS...
January 12, 2018: Oncotarget
Pierre Le Pogam, Mickaël Doué, Yann Le Page, Denis Habauzit, Maxim Zhadobov, Ronan Sauleau, Yves Le Dréan, David Rondeau
The glucose-analogue 2-deoxyglucose (2-DG) impedes cancer progression in animal models and is currently being assessed as an anti-cancer therapy. Yet, the mode of action of this drug of high clinical significance has not been fully delineated. In an attempt to better characterize its pharmacodynamics, an integrative UPLC-Q-Exactive based joint metabolomic and lipidomic approach was undertaken to evaluate the metabolic perturbations induced by this drug in human HaCaT keratinocyte cells. R-XCMS data processing and subsequent multivariate pattern recognition, metabolites identification and pathway analyses identified 8 metabolites that were most significantly changed upon a 3 h 2-DG exposure...
February 12, 2018: Journal of Proteome Research
Ji Young Park, Ae Lee Jeong, Hyun Jeong Joo, Sora Han, So-Hyun Kim, Hye-Youn Kim, Jong-Seok Lim, Myeong-Sok Lee, Hyung-Kyoon Choi, Young Yang
Circulating tumor cells (CTCs) are essential for the establishment of distant metastasis. Numerous studies have characterized CTCs as metastatic precursors; however, the molecular nature of CTCs has not been completely revealed yet due to the low number of CTCs in the blood stream. As an alternative approach, we developed a long-term suspension cell culture model using human breast cancer cell lines to mimic CTCs. We found that more than 40 passaged suspension cells acquired the ability to enhance metastasis like cancer stem cells...
January 2, 2018: Oncotarget
Mandana Hunter, Nicholas J Demarais, Richard L M Faull, Angus C Grey, Maurice A Curtis
The subventricular zone is a key site of adult neurogenesis and is also implicated in neurodegenerative diseases and brain cancers. In the subventricular zone, cell proliferation, migration and differentiation of nascent stem cells and neuroblasts are regulated at least in part by lipids. The human subventricular zone is distinctly layered and each layer contains discrete cell types that support the processes of neuroblast migration and neurogenesis. We set out to determine the lipid signatures of each subventricular layer in the adult human brain (n = 4)...
February 7, 2018: Scientific Reports
Tamara Knific, Katja Vouk, Špela Smrkolj, Cornelia Prehn, Jerzy Adamski, Tea Lanišnik Rižner
In endometrial cancer, biomarkers for preoperative identification of patients with low risk for disease progression would enable stratification according to the extent of surgery needed, and would avoid the complications that can be associated with radical surgery. A panel of proteins, amino acids, enzymes, and miRNA has been investigated as potential biomarkers for endometrial cancer. At the time of the manuscript submission targeted metabolomics/lipidomics approaches have not been applied to biomarker research in endometrial cancer...
January 19, 2018: Journal of Steroid Biochemistry and Molecular Biology
Aiswarya B Pawar, Durba Sengupta
The association of single transmembrane receptors, such as the ErbB receptors is a key event in initiating cell signaling networks. The interactions between these receptors have been well characterized for both ligand-driven and pre-formed dimers. However, the role of the membrane in modulating association is less well understood and assumes greater importance in light of altered membrane composition in diseased states. Here, we discuss how membrane composition has been observed to induce both structural and dynamic differences in receptor association...
January 19, 2018: Journal of Membrane Biology
Ming Chen, Jiangwen Zhang, Katia Sampieri, John G Clohessy, Lourdes Mendez, Enrique Gonzalez-Billalabeitia, Xue-Song Liu, Yu-Ru Lee, Jacqueline Fung, Jesse M Katon, Archita Venugopal Menon, Kaitlyn A Webster, Christopher Ng, Maria Dilia Palumbieri, Moussa S Diolombi, Susanne B Breitkopf, Julie Teruya-Feldstein, Sabina Signoretti, Roderick T Bronson, John M Asara, Mireia Castillo-Martin, Carlos Cordon-Cardo, Pier Paolo Pandolfi
Lipids, either endogenously synthesized or exogenous, have been linked to human cancer. Here we found that PML is frequently co-deleted with PTEN in metastatic human prostate cancer (CaP). We demonstrated that conditional inactivation of Pml in the mouse prostate morphs indolent Pten-null tumors into lethal metastatic disease. We identified MAPK reactivation, subsequent hyperactivation of an aberrant SREBP prometastatic lipogenic program, and a distinctive lipidomic profile as key characteristic features of metastatic Pml and Pten double-null CaP...
January 15, 2018: Nature Genetics
Christoph Schmöcker, Ingrid W Zhang, Stefanie Kiesler, Ursula Kassner, Annika I Ostermann, Elisabeth Steinhagen-Thiessen, Nils H Schebb, Karsten-H Weylandt
Omega-6 polyunsaturated fatty acid (n-6 PUFA) is the predominant polyunsaturated fatty acid (PUFA), especially in Western diet. A high omega-6/omega-3 ratio in Western diets is implicated in the development of cardiovascular diseases and inflammatory processes. Studies in animal models and in humans have demonstrated beneficial effects of omega-3 PUFA (n-3 PUFA) in a variety of diseases, including cardiac arrhythmias and inflammatory diseases, as well as breast and colon cancer. The molecular mechanisms underlying the effects of n-3 PUFA are still not well understood...
January 8, 2018: International Journal of Molecular Sciences
Farshad Farshidfar, Karen A Kopciuk, Robert Hilsden, S Elizabeth McGregor, Vera C Mazurak, W Donald Buie, Anthony MacLean, Hans J Vogel, Oliver F Bathe
BACKGROUND: Early diagnosis of colorectal cancer (CRC) simplifies treatment and improves treatment outcomes. We previously described a diagnostic metabolomic biomarker derived from semi-quantitative gas chromatography-mass spectrometry. Our objective was to determine whether a quantitative assay of additional metabolomic features, including parts of the lipidome could enhance diagnostic power; and whether there was an advantage to deriving a combined diagnostic signature with a broader metabolomic representation...
January 4, 2018: BMC Cancer
Zongtao Yu, Hankui Chen, Junmei Ai, Yong Zhu, Yan Li, Jeffrey A Borgia, Jin-Song Yang, Jicai Zhang, Bin Jiang, Wei Gu, Youping Deng
Purpose: Lipids play roles in membrane structure, energy storage, and signal transduction as well as in human cancers. Here we adopt lipidomics to identify plasma lipid markers for early screening and detection of lung cancer. Experimental Design: Using mass spectrometry, we profiled 390 individual lipids using training and validation strategy in a total of 346 plasma samples from 199 early NSCLC patients, including 113 adenocacinoma and 86 squamous cell cancers (SqCC), and from 147 healthy controls...
December 8, 2017: Oncotarget
Yi-Hsuan Lai, Hsuan Liu, Wei-Fan Chiang, Ting-Wen Chen, Lichieh Julie Chu, Jau-Song Yu, Shu-Jen Chen, Hua-Chien Chen, Bertrand Chin-Ming Tan
During neoplastic development, a multitude of changes in genome-encoded information are progressively selected to confer growth and survival advantages to tumor cells. microRNAs-mRNAs regulatory networks, given their role as a critical layer of robust gene expression control, are frequently altered in neoplasm. However, whether and how these gene perturbations impact metabolic homeostasis remains largely unresolved. Methods: Through targeted miRNA expression screening, we uncovered an oral squamous cell carcinoma (OSCC)-associated miRNAome, among which miR-31-5p was identified based on extent of up-regulation, functional impact on OSCC cell migration and invasion, and direct regulation of the rate-limiting enzyme in peroxisomal β-oxidation, ACOX1...
2018: Theranostics
Lu Dai, Charles D Smith, Maryam Foroozesh, Lucio Miele, Zhiqiang Qin
Non-small cell lung cancer (NSCLC) accounts for about 85-90% of lung cancer cases, and is the number one killer among cancers in the United States. The majorities of lung cancer patients do not respond well to conventional chemo- and/or radio-therapeutic regimens, and have a dismal 5-year survival rate of ∼15%. The recent introduction of targeted therapy and immunotherapy gives new hopes to NSCLC patients, but even with these agents, not all patients respond, and responses are rarely complete. Thus, there is still an urgent need to identify new therapeutic targets in NSCLC and develop novel anti-cancer agents...
December 26, 2017: International Journal of Cancer. Journal International du Cancer
Zuzana Tylichová, Josef Slavík, Miroslav Ciganek, Petra Ovesná, Pavel Krčmář, Nicol Straková, Miroslav Machala, Alois Kozubík, Jiřina Hofmanová, Jan Vondráček
Docosahexaenoic acid (DHA) and sodium butyrate (NaBt) exhibit a number of interactive effects on colon cancer cell growth, differentiation or apoptosis; however, the molecular mechanisms responsible for these interactions and their impact on cellular lipidome are still not fully clear. Here, we show that both dietary agents together induce dynamic alterations of lipid metabolism, specific cellular lipid classes and fatty acid composition. In HT-29 cell line, a model of differentiating colon carcinoma cells, NaBt supported incorporation of free DHA into non-polar lipids and their accumulation in cytoplasmic lipid droplets...
December 23, 2017: Journal of Cellular Biochemistry
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