OBJECTIVE: Ascites, an accumulation of peritoneal fluid, is associated with poor prognosis of certain cancers. The potential mechanism that ascites worsens prognosis has not been well understood. Lipids have been reported to correlate with the prognosis of patients with epithelial ovarian cancer (EOC). Therefore, we aimed here to investigate whether lipids mediate the effect of ascites on the recurrence of EOC. METHODS: We collected the demographic and pathological data of 437 previously untreated patients with EOC to investigate the influence of ascites on recurrence. To identify the mechanism that mediates the potential influence of ascites on recurrence, we used ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) to determine the plasma lipid profiles of 53 patients with EOC. We used mediation analysis to evaluate if lipids mediated the effects of ascites on the recurrence of EOC. RESULTS: Patients with ascites had a poorer prognosis, which was associated with higher levels of carbohydrate antigen-CA125 (CA125) and FIGO stage. We identified six different lipid metabolites that were associated with ascites and recurrence. Mediation analysis revealed that the lipids LysoPC(P-15:0), PC(P-34:4), and PC(38:6) may mediate the effects of ascites on recurrence. CONCLUSION: Our findings suggest that LysoPC(P-15:0), PC(P-34:4), and PC(38:6) mediate the effect of ascites on the prognosis of patients with EOC. We believe therefore that it is reasonable to consider metabolic interventions targeting the metabolism of LysoPC(P-15:0), PC(P-34:4), and PC(38:6) as a palliative treatment for patients with EOC with ascites. Further studies of more patients will be required to validate our findings.
OBJECTIVE: Ascites, an accumulation of peritoneal fluid, is associated with poor prognosis of certain cancers. The potential mechanism that ascites worsens prognosis has not been well understood. Lipids have been reported to correlate with the prognosis of patients with epithelial ovarian cancer (EOC). Therefore, we aimed here to investigate whether lipids mediate the effect of ascites on the recurrence of EOC. METHODS: We collected the demographic and pathological data of 437 previously untreated patients with EOC to investigate the influence of ascites on recurrence. To identify the mechanism that mediates the potential influence of ascites on recurrence, we used ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) to determine the plasma lipid profiles of 53 patients with EOC. We used mediation analysis to evaluate if lipids mediated the effects of ascites on the recurrence of EOC. RESULTS: Patients with ascites had a poorer prognosis, which was associated with higher levels of carbohydrate antigen-CA125 (CA125) and FIGO stage. We identified six different lipid metabolites that were associated with ascites and recurrence. Mediation analysis revealed that the lipids LysoPC(P-15:0), PC(P-34:4), and PC(38:6) may mediate the effects of ascites on recurrence. CONCLUSION: Our findings suggest that LysoPC(P-15:0), PC(P-34:4), and PC(38:6) mediate the effect of ascites on the prognosis of patients with EOC. We believe therefore that it is reasonable to consider metabolic interventions targeting the metabolism of LysoPC(P-15:0), PC(P-34:4), and PC(38:6) as a palliative treatment for patients with EOC with ascites. Further studies of more patients will be required to validate our findings.
Authors: Natalie Fisher; Michael G Edwards; Ryan Hemming; Steven M Allin; John D Wallis; Philip C Bulman Page; Michael J Mckenzie; Stefanie M Jones; Mark R J Elsegood; John King-Underwood; Alan Richardson Journal: J Med Chem Date: 2018-08-15 Impact factor: 7.446
Authors: Maartje C A Wouters; Fenne L Komdeur; Hagma H Workel; Harry G Klip; Annechien Plat; Neeltje M Kooi; G Bea A Wisman; Marian J E Mourits; Henriette J G Arts; Maaike H M Oonk; Refika Yigit; Steven de Jong; Cornelis J M Melief; Harry Hollema; Evelien W Duiker; Toos Daemen; Marco de Bruyn; Hans W Nijman Journal: Clin Cancer Res Date: 2015-09-18 Impact factor: 12.531
Authors: Nirmala Chandralega Kampan; Mutsa Tatenda Madondo; Orla M McNally; Andrew N Stephens; Michael A Quinn; Magdalena Plebanski Journal: Front Immunol Date: 2017-11-06 Impact factor: 7.561
Authors: Melissa N Barber; Steve Risis; Christine Yang; Peter J Meikle; Margaret Staples; Mark A Febbraio; Clinton R Bruce Journal: PLoS One Date: 2012-07-25 Impact factor: 3.240