Higher plasma levels of lysophosphatidylcholine 18:0 are related to a lower risk of common cancers in a prospective metabolomics study

Kühn, Tilman; Floegel, Anna; Sookthai, Disorn; Johnson, Theron; Rolle-Kampczyk, Ulrike; Otto, Wolfgang; Bergen, Martin von; Boeing, Heiner; Kaaks, Rudolf

doi:10.1186/s12916-016-0552-3

Cited by 172 publications

(186 citation statements)

References 39 publications

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“…Moreover, seven LysoPCs were detected at lower levels among colorectal cancer patients compared to controls. LysoPC (16:0) and LysoPC (18:0) were reported before to be lower in the plasma of colorectal cancer patients versus control individuals . There seems to be a general trend of lower levels of LysoPCs among colorectal cancer patients in existing studies, which is in line with the findings reported in our study.…”

Section: Discussionsupporting

confidence: 92%

Plasma metabolites associated with colorectal cancer: A discovery‐replication strategy

Geijsen

Brezina

Keski‐Rahkonen

et al. 2019

Intl Journal of Cancer

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Colorectal cancer is known to arise from multiple tumorigenic pathways; however, the underlying mechanisms remain not completely understood. Metabolomics is becoming an increasingly popular tool in assessing biological processes. Previous metabolomics research focusing on colorectal cancer is limited by sample size and did not replicate findings in independent study populations to verify robustness of reported findings. Here, we performed a ultrahigh performance liquid chromatography‐quadrupole time‐of‐flight mass spectrometry (UHPLC‐QTOF‐MS) screening on EDTA plasma from 268 colorectal cancer patients and 353 controls using independent discovery and replication sets from two European cohorts (ColoCare Study: n = 180 patients/n = 153 controls; the Colorectal Cancer Study of Austria (CORSA) n = 88 patients/n = 200 controls), aiming to identify circulating plasma metabolites associated with colorectal cancer and to improve knowledge regarding colorectal cancer etiology. Multiple logistic regression models were used to test the association between disease state and metabolic features. Statistically significant associated features in the discovery set were taken forward and tested in the replication set to assure robustness of our findings. All models were adjusted for sex, age, BMI and smoking status and corrected for multiple testing using False Discovery Rate. Demographic and clinical data were abstracted from questionnaires and medical records.

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Section: Discussionsupporting

confidence: 92%

Plasma metabolites associated with colorectal cancer: A discovery‐replication strategy

Geijsen

Brezina

Keski‐Rahkonen

et al. 2019

Intl Journal of Cancer

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“…Overexpression of ATX and LysoPA has been observed in several cancers, including glioblastoma, thyroid carcinomas, and renal cell carcinoma27. Since both ATX and LysoPA receptor knockout mice show lower cancer risk, overexpression of ATX and LysoPA receptors has been proposed to be a common feature of several cancers29. In our results, we found that LPCAT1 and ATX were highly expressed in melanoma tissues and B16-F10 cancer cells (Fig.…”

Section: Discussionsupporting

confidence: 60%

“…A prospective metabolomics study showed that higher levels of LysoPC 18:0 were related to a lower risk of common cancers. In contrast, higher levels of PC were associated with increased cancer risk29. Moreover, Jantscheff et al .…”

Section: Discussionmentioning

confidence: 96%

Anti-melanoma activity of Forsythiae Fructus aqueous extract in mice involves regulation of glycerophospholipid metabolisms by UPLC/Q-TOF MS-based metabolomics study

Bao

Liu

Zhang

et al. 2016

Sci Rep

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Metabolomics is a comprehensive assessment of endogenous metabolites of a biological system in a holistic context. In this study, we evaluated the in vivo anti-melanoma activity of aqueous extract of Forsythiae Fructus (FAE) and globally explored the serum metabolome characteristics of B16-F10 melanoma-bearing mice. UPLC/Q-TOF MS combined with pattern recognition approaches were employed to examine the comprehensive metabolic signatures and differentiating metabolites. The results demonstrated that FAE exhibited remarkable antitumor activity against B16-F10 melanoma in C57BL/6 mice and restored the disturbed metabolic profile by tumor insult. We identified 17 metabolites which were correlated with the antitumor effect of FAE. Most of these metabolites are involved in glycerophospholipid metabolisms. Notably, several lysophosphatidylcholines (LysoPCs) significantly decreased in tumor model group, while FAE treatment restored the changes of these phospholipids to about normal condition. Moreover, we found that lysophosphatidylcholine acyltransferase 1 (LPCAT1) and autotaxin (ATX) were highly expressed in melanoma, and FAE markedly down-regulated their expression. These findings indicated that modulation of glycerophospholipid metabolisms may play a pivotal role in the growth of melanoma and the antitumor activity of FAE. Besides, our results suggested that serum LysoPCs could be potential biomarkers for the diagnosis and prognosis of melanoma and other malignant tumors.

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“…Using metabolomics, which measures large numbers of small molecules in body fluids reflecting internal (the genome, epigenome, transcriptome and proteome) and external factors (diet, lifestyle, environment and gut microbiota), may help to identify novel risk factors for prostate cancer. Previously, relatively small prospective studies ( n cases = 74–1,077), including our study in the European Prospective Investigation into Cancer and Nutrition (EPIC), showed that men with higher circulating concentrations of lipids and/or energy‐related metabolites might have lower risk of prostate cancer, especially more aggressive tumor subtypes . Moreover, a prospective study of lethal prostate cancer reported associations with metabolites in redox (inverse), dipeptide (positive), pyrimidine (mostly positive) and gamma‐glutamyl amino acid (positively) pathways ( n deaths = 523) .…”

Section: Introductionmentioning

confidence: 60%

Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case–control sets from EPIC

Schmidt

Fensom

Rinaldi

et al. 2019

Intl Journal of Cancer

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Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case–control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR1SD) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR1SD = 0.77, 95% confidence interval 0.66–0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR1SD = 0.72, 0.57–0.90), or lysophosphatidylcholines (OR1SD = 0.81, 0.69–0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow‐up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR1SD = 0.77, 0.61–0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.

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Higher plasma levels of lysophosphatidylcholine 18:0 are related to a lower risk of common cancers in a prospective metabolomics study

Cited by 172 publications

References 39 publications

Plasma metabolites associated with colorectal cancer: A discovery‐replication strategy

Plasma metabolites associated with colorectal cancer: A discovery‐replication strategy

Anti-melanoma activity of Forsythiae Fructus aqueous extract in mice involves regulation of glycerophospholipid metabolisms by UPLC/Q-TOF MS-based metabolomics study

Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case–control sets from EPIC

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