Skip to main content
Erschienen in: Tumor Biology 4/2016

13.11.2015 | Original Article

Identification of phosphatidylcholine and lysophosphatidylcholine as novel biomarkers for cervical cancers in a prospective cohort study

verfasst von: Ming-zhu Yin, Shu Tan, Xia Li, Yan Hou, Guosheng Cao, Kang Li, Junping Kou, Ge Lou

Erschienen in: Tumor Biology | Ausgabe 4/2016

Einloggen, um Zugang zu erhalten

Abstract

Metabolites are the end products of cellular regulatory processes. Squamous cervical cancer (SCC) can alter the level of certain small molecular metabolite in plasma through modulating gene expression. In this study, we identified two metabolites, phosphatidylcholine (PC) and lysophosphatidylcholine (LPC), which are significantly down- and upregulated in plasma of SCC as compared to uterine fibroid (UF) patients via ultra-performance liquid chromatographic-mass spectrometry (UPLC-MS). In external prospective cohort, our assay has a sensitivity of 93.2 %, a specificity of 91.3 %, and an area under the receiver operating characteristic (ROC) curve (AUC) of 0.972. The level of LPC is significantly higher in SCC than in UF patients. An opposite result was observed in PC level. Our findings suggest that the PC and lysoPC could be used as novel biomarkers to facilitate SCC diagnosis.
Literatur
1.
Zurück zum Zitat Nicholson JK, Lindon JC, Holmes E. ‘Metabonomics’: understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica. 1999;29(11):1181–9.CrossRefPubMed Nicholson JK, Lindon JC, Holmes E. ‘Metabonomics’: understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica. 1999;29(11):1181–9.CrossRefPubMed
2.
Zurück zum Zitat Fiehn O. Metabolomics—the link between genotypes and phenotypes. Plant Mol Biol. 2002;48:155–71.CrossRefPubMed Fiehn O. Metabolomics—the link between genotypes and phenotypes. Plant Mol Biol. 2002;48:155–71.CrossRefPubMed
3.
Zurück zum Zitat Welthagen W, Shellie R, Ristow M, Spranger J, Zimmermann R, Fiehn O. Comprehensive two dimensional gas chromatography-time of flight mass spectrometry, GCxGC-TOF for high resolution metabolomics: biomarker discovery on spleen tissue extracts of obese NZO compared to lean C57BL/6 mice. Metabolomics. 2005;1:57–65.CrossRef Welthagen W, Shellie R, Ristow M, Spranger J, Zimmermann R, Fiehn O. Comprehensive two dimensional gas chromatography-time of flight mass spectrometry, GCxGC-TOF for high resolution metabolomics: biomarker discovery on spleen tissue extracts of obese NZO compared to lean C57BL/6 mice. Metabolomics. 2005;1:57–65.CrossRef
4.
Zurück zum Zitat Wang X, Sun H, Zhang A, Wang P, Han Y. Ultra-performance liquid chromatography coupled to mass spectrometry as a sensitive and powerful technology for metabolomic studies. J Sep Sci. 2011;34(24):3451–9. Review.CrossRefPubMed Wang X, Sun H, Zhang A, Wang P, Han Y. Ultra-performance liquid chromatography coupled to mass spectrometry as a sensitive and powerful technology for metabolomic studies. J Sep Sci. 2011;34(24):3451–9. Review.CrossRefPubMed
5.
Zurück zum Zitat Gouveia MJ, Brindley PJ, Santos LL, da Costa JM C, Gomes P, Vale N. Mass spectrometry techniques in the survey of steroid metabolites as potential disease biomarkers: a review. Metabolism. 2013;62(9):1206–17.CrossRefPubMedPubMedCentral Gouveia MJ, Brindley PJ, Santos LL, da Costa JM C, Gomes P, Vale N. Mass spectrometry techniques in the survey of steroid metabolites as potential disease biomarkers: a review. Metabolism. 2013;62(9):1206–17.CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Odunsi K, Wollman RM, Ambrosome CB, Hutson A, McCann SE, Tammela J, et al. Detection of epithelial ovarian cancer using H-1-NMR-based metabonomics. Int J Cancer. 2005;113:782–8.CrossRefPubMed Odunsi K, Wollman RM, Ambrosome CB, Hutson A, McCann SE, Tammela J, et al. Detection of epithelial ovarian cancer using H-1-NMR-based metabonomics. Int J Cancer. 2005;113:782–8.CrossRefPubMed
7.
Zurück zum Zitat Slupsky CM, Steed H, Wells TH, Dabbs K, Schepansky A, Capstick V, et al. Urine metabolite analysis offers potential early diagnosis of ovarian and breast cancers. Clin Cancer Res. 2010;16(23):5835–41.CrossRefPubMed Slupsky CM, Steed H, Wells TH, Dabbs K, Schepansky A, Capstick V, et al. Urine metabolite analysis offers potential early diagnosis of ovarian and breast cancers. Clin Cancer Res. 2010;16(23):5835–41.CrossRefPubMed
8.
Zurück zum Zitat Abate-Shen C, Shen MM. Diagnostics. The prostate-cancer metabolome. Nature. 2009;457(7231):799–800.CrossRefPubMed Abate-Shen C, Shen MM. Diagnostics. The prostate-cancer metabolome. Nature. 2009;457(7231):799–800.CrossRefPubMed
9.
Zurück zum Zitat Pasikanti KK, Esuvaranathan K, Ho PC, Mahendran R, Kamaraj R, Wu QH, et al. Noninvasive urinary metabonomic diagnosis of human bladder cancer. J Proteome Res. 2010;9(6):2988–95.CrossRefPubMed Pasikanti KK, Esuvaranathan K, Ho PC, Mahendran R, Kamaraj R, Wu QH, et al. Noninvasive urinary metabonomic diagnosis of human bladder cancer. J Proteome Res. 2010;9(6):2988–95.CrossRefPubMed
10.
Zurück zum Zitat Zhang T, Wu X, Ke C, Yin M, Li Z, Fan L, et al. Identification of potential biomarkers for ovarian cancer by urinary metabolomic profiling. J Proteome Res. 2013;12(1):505–12.CrossRefPubMed Zhang T, Wu X, Ke C, Yin M, Li Z, Fan L, et al. Identification of potential biomarkers for ovarian cancer by urinary metabolomic profiling. J Proteome Res. 2013;12(1):505–12.CrossRefPubMed
11.
Zurück zum Zitat Hou Y, Yin M, Sun F, Zhang T, Zhou X, Li H, et al. A metabolomics approach for predicting the response to neoadjuvant chemotherapy in cervical cancer patients. Mol Biosyst. 2014;10(8):2126–33.CrossRefPubMed Hou Y, Yin M, Sun F, Zhang T, Zhou X, Li H, et al. A metabolomics approach for predicting the response to neoadjuvant chemotherapy in cervical cancer patients. Mol Biosyst. 2014;10(8):2126–33.CrossRefPubMed
12.
Zurück zum Zitat Yin M, Zhao F, Lou G, Zhang H, Sun M, Li C, et al. The long-term efficacy of neoadjuvant chemotherapy followed by radical hysterectomy compared with radical surgery alone or concurrent chemoradiotherapy on locally advanced-stage cervical cancer. Int J Gynecol Cancer. 2011;21(1):92–9.PubMed Yin M, Zhao F, Lou G, Zhang H, Sun M, Li C, et al. The long-term efficacy of neoadjuvant chemotherapy followed by radical hysterectomy compared with radical surgery alone or concurrent chemoradiotherapy on locally advanced-stage cervical cancer. Int J Gynecol Cancer. 2011;21(1):92–9.PubMed
13.
Zurück zum Zitat Yin M, Zhang H, Li H, Li X, Liu Y, Chen X, et al. The toxicity and long-term efficacy of nedaplatin and paclitaxel treatment as neoadjuvant chemotherapy for locally advanced cervical cancer. J Surg Oncol. 2012;105(2):206–11.CrossRefPubMed Yin M, Zhang H, Li H, Li X, Liu Y, Chen X, et al. The toxicity and long-term efficacy of nedaplatin and paclitaxel treatment as neoadjuvant chemotherapy for locally advanced cervical cancer. J Surg Oncol. 2012;105(2):206–11.CrossRefPubMed
14.
Zurück zum Zitat Rob L, Halaska M, Robova H. Nerve-sparing and individually tailored surgery for cervical cancer. Lancet Oncol. 2010;11(3):292–301. Review.CrossRefPubMed Rob L, Halaska M, Robova H. Nerve-sparing and individually tailored surgery for cervical cancer. Lancet Oncol. 2010;11(3):292–301. Review.CrossRefPubMed
15.
Zurück zum Zitat Lin HM, Barnett MP, Roy NC, Joyce NI, Zhu S, Armstrong K, et al. Metabolomic analysis identifies inflammatory and noninflammatory metabolic effects of genetic modification in a mouse model of Crohn’s disease. J Proteome Res. 2010;9(4):1965–75.CrossRefPubMed Lin HM, Barnett MP, Roy NC, Joyce NI, Zhu S, Armstrong K, et al. Metabolomic analysis identifies inflammatory and noninflammatory metabolic effects of genetic modification in a mouse model of Crohn’s disease. J Proteome Res. 2010;9(4):1965–75.CrossRefPubMed
16.
Zurück zum Zitat Zhang J, Yan L, Chen W, Lin L, Song X, Yan X, et al. Metabonomics research of diabetic nephropathy and type 2 diabetes mellitus based on UPLC-oaTOF-MS system. Anal Chim Acta. 2009;650(1):16–22.CrossRefPubMed Zhang J, Yan L, Chen W, Lin L, Song X, Yan X, et al. Metabonomics research of diabetic nephropathy and type 2 diabetes mellitus based on UPLC-oaTOF-MS system. Anal Chim Acta. 2009;650(1):16–22.CrossRefPubMed
17.
Zurück zum Zitat Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982;143:29–36.CrossRefPubMed Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982;143:29–36.CrossRefPubMed
18.
Zurück zum Zitat Wishart DS, Knox C, Guo AC, Eisner R, Young N, Gautam B, et al. HMDB: a knowledgebase for the human metabolome. Nucleic Acids Res. 2009;37:603–10.CrossRef Wishart DS, Knox C, Guo AC, Eisner R, Young N, Gautam B, et al. HMDB: a knowledgebase for the human metabolome. Nucleic Acids Res. 2009;37:603–10.CrossRef
19.
Zurück zum Zitat Smith CA, Maille OG, Want EJ, Qin C, Trauger SA, Brandon TR, et al. METLIN: a metabolite mass spectral database. Ther Drug Monit. 2005;27:747–51.CrossRefPubMed Smith CA, Maille OG, Want EJ, Qin C, Trauger SA, Brandon TR, et al. METLIN: a metabolite mass spectral database. Ther Drug Monit. 2005;27:747–51.CrossRefPubMed
20.
Zurück zum Zitat Kjaer S, Hodall E, Frederiksen K, Munk C, van den Brule A, Svare E, et al. The absolute risk of cervical abnormalities in high-risk human papillomavirus-positive, cytologically normal women over a 10-year period. Cancer Res. 2006;66(21):10630–6.CrossRefPubMed Kjaer S, Hodall E, Frederiksen K, Munk C, van den Brule A, Svare E, et al. The absolute risk of cervical abnormalities in high-risk human papillomavirus-positive, cytologically normal women over a 10-year period. Cancer Res. 2006;66(21):10630–6.CrossRefPubMed
21.
Zurück zum Zitat Asaoka Y, Yoshida K, Sasaki Y, Nishizuka Y. Potential role of phospholipase A2 in HL-60 cell differentiation to macrophages induced by protein kinase C activation. Proc nat Acad Sci (Wash). 1993;90:4917–21.CrossRef Asaoka Y, Yoshida K, Sasaki Y, Nishizuka Y. Potential role of phospholipase A2 in HL-60 cell differentiation to macrophages induced by protein kinase C activation. Proc nat Acad Sci (Wash). 1993;90:4917–21.CrossRef
22.
Zurück zum Zitat Yoshida K, Asaoka Y, Nishizuka Y. Platelet activation by simultaneous actions of diacylglycerol and unsaturated fatty acids. Proc nat Acad Sci (Wash). 1992;89:6443–6.CrossRef Yoshida K, Asaoka Y, Nishizuka Y. Platelet activation by simultaneous actions of diacylglycerol and unsaturated fatty acids. Proc nat Acad Sci (Wash). 1992;89:6443–6.CrossRef
23.
24.
Zurück zum Zitat Podo F, Sardanelli F, Iorio E, Canese R, Carpinelli G, Alfonso F. Abnormal choline phospholipid metabolism in breast and ovary cancer: molecular bases for noninvasive imaging approaches. Curr Mol Imag Rev. 2007;3:123–37.CrossRef Podo F, Sardanelli F, Iorio E, Canese R, Carpinelli G, Alfonso F. Abnormal choline phospholipid metabolism in breast and ovary cancer: molecular bases for noninvasive imaging approaches. Curr Mol Imag Rev. 2007;3:123–37.CrossRef
25.
Zurück zum Zitat Ackerstaff E, Pflug BR, Nelson JB, Bhujwalla ZM. Detection of increased choline compounds with proton nuclear magnetic resonance spectroscopy subsequent to malignant transformation of human prostatic epithelial cells. Cancer Res. 2001;61:3599–603.PubMed Ackerstaff E, Pflug BR, Nelson JB, Bhujwalla ZM. Detection of increased choline compounds with proton nuclear magnetic resonance spectroscopy subsequent to malignant transformation of human prostatic epithelial cells. Cancer Res. 2001;61:3599–603.PubMed
26.
Zurück zum Zitat Iorio E, Mezzanzanica D, Alberti P, Spadaro F, Ramoni C, D’Ascenzo S, et al. Alterations of choline phospholipid metabolism in ovarian tumor progression. Cancer Res. 2005;65:9369–76.CrossRefPubMed Iorio E, Mezzanzanica D, Alberti P, Spadaro F, Ramoni C, D’Ascenzo S, et al. Alterations of choline phospholipid metabolism in ovarian tumor progression. Cancer Res. 2005;65:9369–76.CrossRefPubMed
27.
Zurück zum Zitat Glunde K, Ackerstaff E, Mori N, Jacobs MA, Bhujwalla ZM. Choline phospholipid metabolism in cancer: consequences for molecular pharmaceutical interventions. Mol Pharm. 2006;3:496–506.CrossRefPubMed Glunde K, Ackerstaff E, Mori N, Jacobs MA, Bhujwalla ZM. Choline phospholipid metabolism in cancer: consequences for molecular pharmaceutical interventions. Mol Pharm. 2006;3:496–506.CrossRefPubMed
28.
Zurück zum Zitat Lunde K, Serkova NJ. Therapeutic targets and biomarkers identified in cancer choline phospholipid metabolism. Pharmacogenomics. 2006;7:1109–23.CrossRef Lunde K, Serkova NJ. Therapeutic targets and biomarkers identified in cancer choline phospholipid metabolism. Pharmacogenomics. 2006;7:1109–23.CrossRef
29.
Zurück zum Zitat Okita M, Gaudette DC, Mills GB, Holub BJ. Elevated levels and altered fatty acid composition of plasma lysophosphatidylcholine (lysoPC) in ovarian cancer patients. Int J Cancer. 1997;71(1):31–4.CrossRefPubMed Okita M, Gaudette DC, Mills GB, Holub BJ. Elevated levels and altered fatty acid composition of plasma lysophosphatidylcholine (lysoPC) in ovarian cancer patients. Int J Cancer. 1997;71(1):31–4.CrossRefPubMed
Metadaten
Titel
Identification of phosphatidylcholine and lysophosphatidylcholine as novel biomarkers for cervical cancers in a prospective cohort study
verfasst von
Ming-zhu Yin
Shu Tan
Xia Li
Yan Hou
Guosheng Cao
Kang Li
Junping Kou
Ge Lou
Publikationsdatum
13.11.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 4/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4164-x

Weitere Artikel der Ausgabe 4/2016

Tumor Biology 4/2016 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.