Serum Lipidomics Study Of Patients With POEMS Syndrome

BackgroundPOEMS syndrome is a rare plasma cell dyscrasia characterized by polyneuropathy,organomegaly,endocrinopathy,monoclonal gammopathy and skin changes.Most patients had shrinking buccal pad fat and weight loss at disease onset,indicating lipid metabolism disorders.Manifestation of POEMS syndrome,such as the elevated serum level of vascular endothelial growth factor,may also be mediated by lipids.Many studies have shown that lipid metabolism is significantly altered in a variety of cancers.Serum cholesterol levels declined at onset of most cancerous diseases,while triglycerides increased,In addition to lipids in routine biochemical tests,the serum lipidome characteristics detected by mass spectrometry also showed prognostic value in cancers.However,the characteristics of lipid metabolism in patients with POEMS syndrome have not been described.Objective1.Quantitative description of body fat rate and distribution in patients with POEMS syndrome at disease onset by dual-energy X-ray absorptiometry.2.To describe the baseline lipid characteristic of POEMS patients,compared with normal people,and after treatment.3.To establish a prognostic model based on baseline lipid profile characteristics.MethodIn the first part,22 POEMS syndrome patients newly diagnosed at Peking Union Medical College Hospital from November,2018 to May,2019 were prospectively enrolled.The body composition data was collected by dual-energy X-ray absorptiometry,and the relationships between fat mass index,body mass index and risk stratification were investigated.In the second part,24 POEMS syndrome patients newly-diagnosed at Peking Union Medical College from September,2017 to July,2018 were extracted from our database.All patients had baseline and follow-up serum after at least one cycle of treatment.Twenty-four healthy people who underwent physical examination in Peking Union Medical College Hospital in November,2018 and met the enrollment criteria were selected.We intend to establish a diagnostic model between patients and normal people.In the third part,33 POEMS syndrome patients newly diagnosed at our centre from April 2014 to December 2017 were extracted from our database.All patients were treated with lenalidomide combined with dexamethasone.After regularly followed up to March 2019,15 patients relapsed and 18 patients were relapse-free.Non-targeted lipidome data in baseline serum of patients was collected by liquid chromatograph mass specfrometry.Altered lipids in baseline serum between relapsed and non-relapsed patients were identified,and a baseline-lipids-based prognostie model was established.Result1.Nearly 70%POEMS syndrome patients had obvious fat deficiency at disease onset,with severe fat deficiency taking up of 80%of fat deficiency patients.The abdominal(android)fat loss was more prominent.Severe body fat deficiency and the android/gynoid ratio less than 1 was associated with higher risk.2.Patients had a lipid characteristie distinct from normal people,which is characterized by a decrease of fatty acyls and glycerolipids.The baseline serum 17-oxo-20Z-hexacosenoic acid was independently associated with patients(OR 1.07,95%CI1.01-1.13,p=0.021).A two-fatty-acyl lipid model could be constructed to based on 17-oxo-20Z-hexacosenoic acid and Q-3 arachidonic acid to distinguish patients and healthy people at 100%accuracy.Baseline serum glycosphingolipid AS 1-1 and glycerophospholipid LysoPC(20:4)was higher in patients than healthy control.Both were reported to promote tumor cell invasion and metastasis.PE and PC increased significantly in patients with body fat deficiency,suggesting the upregulated Kennedy pathway.3.The baseline serum level of EPA was significantly lower in patient with CRH during follow-up than patients without CRH,and was independently correlated with progression.(HR 1.000,95%Cl 1.000-1.001,p=0.035)Based on EPA and PA(15:0/22:1(11Z))level above or below the average level,a prediction model was constructed.Patients with both lipids below average level had a significantly prolonged PFS than patients with either lipid above the average level.(p=0.001)Conclusion1.Fat deficiency was prevalent in POEMS syndrome patients at disease onset.Severe fat deficiency was associated with higher risk.2.POEMS syndrome patients had a distinct lipid characteristic from healthy control,characterized by a decrease of fatty acyls and glycerolipids.A two-lipids model could distinguish patients and healthy people with high accuracy,3.The prognostic model was constructed based on EPA and a PA lipid.