骨髓脂肪细胞因子与骨髓增生异常综合征的相关性研究

Study on the correlation between bone marrow adipocytokines and myelodysplastic syndromes

    摘要
  • 摘要:
      目的  研究骨髓脂肪细胞因子与骨髓增生异常综合征（myelodysplastic syndromes，MDS）发生、进展及预后的关系。
      方法  回顾性分析2020年2月至2022年2月郑州大学附属肿瘤医院治疗的采用酶联免疫吸附法（ELISA）检测的72例MDS和16例MDS继发急性髓系白血病（secondary acute myeloid leukemia，sAML）患者骨髓上清液中的脂肪细胞因子，包括脂联素（adiponectin，ADP）、瘦素（leptin，LEP）、内脏脂肪素（nicotinamide phosphoribosyltransferase，NAMPT）、降脂素（complement factor D，CFD）和人补体C1q肿瘤坏死因子相关蛋白1（C1q/TNF-related protein 1，CTRP1）。对其中70例患者采用高通量测序靶向检测78种血液肿瘤相关基因，分析脂肪细胞因子与患者临床特征、疾病亚型、异常基因和预后等的关系。
      结果  临床特征相关结果显示，男性ADP和LEP水平分别较女性显著降低（P=0.027，P=0.019）；年龄<65岁患者的ADP、CFD和NAMPT水平较年龄≥65岁患者显著降低（P=0.020，P<0.001，P=0.021），而LEP水平显著升高（P=0.043）；体质量指数（BMI）<24 kg/m2患者ADP水平较BMI≥24 kg/m2患者显著升高（P=0.025），而LEP水平显著降低（P=0.020）；原始细胞升高组的NAMPT水平较无原始细胞升高组显著升高（P=0.037）；MDS组的CTRP1水平较sAML组显著升高（P=0.010）。异常基因相关分析显示，CTRP1水平的升高与表观遗传相关异常基因的发生呈正相关（P=0.001），与TET2和U2AF1的发生呈正相关（P<0.001，P=0.036）；ADP和CFD水平分别与NPM1的发生呈正相关（P=0.048，P=0.026）。多因素Cox回归生存分析显示，LEP<0.2 ng/mL是MDS患者无进展生存期（progression-free survival，PFS）和总生存期（overall survival，OS）的独立危险因素（P=0.002，P<0.001），而NAMPT<2.1 ng/mL是MDS患者PFS的保护因素（P=0.043）。
      结论  骨髓微环境中脂肪细胞因子与MDS患者一般特征、基因突变以及预后密切相关，其中LEP<0.2 ng/mL是MDS患者独立的预后危险因素，而NAMPT<2.1 ng/mL是预后保护因素。

     

    Abstract:
      Objective  To explore the relationship between adipocytokine levels in bone marrow and the onset, progression, and prognosis of myelodysplastic syndromes (MDS).
      Methods  Retrospective analysis of adipocytokine levels in the bone marrow of 72 patients with MDS and 16 patients with MDS-related secondary acute myeloid leukemia (sAML), including adiponectin (ADP), leptin (LEP), visfatin/nicotinamide phosphoribosyltransferase (NAMPT), adipsin/complement factor D (CFD), and C1q/TNF-related protein 1 (CTRP1), detected by enzyme-linked immunosorbent assay (ELISA) at The Affiliated Cancer Hospital of Zhengzhou University from February 2020 to February 2022. High-throughput sequencing was used to detect MDS-related genes in 70 patients and the relationship between adipocytokines and the clinical characteristics, disease subtypes, mutant genes, and prognosis of patients were analyzed. Seventy-eight MDS-related genes were identified.
      Results  Clinical characteristics showed that ADP (P=0.027) and LEP (P=0.019) levels were significantly lower in men than inwomen; ADP (P=0.020), CFD (P<0.001), and NAMPT (P=0.021) levels were significantly lower in patients aged <65 years than in patients aged ≥65, whereas LEP levels were significantly higher (P=0.043). Adiponectin levels were significantly higher in patients with BMI<24 than in patients with BMI≥24 (P=0.025), whereas LEP levels were significantly lower (P=0.020); NAMPT levels were significantly higher in the group with increased blasts than in the group with no blasts (P=0.037).The CTRP1 levels were significantly higher in the MDS group than in the sAML group (P=0.010). Abnormal gene correlation analysis showed that elevated CTRP1 levels were positively correlated with the occurrence of epigenetically related abnormal genes (P=0.001) and were positively correlated with the occurrence of TET2 and U2AF1 (P<0.001 and P=0.036, respectively); ADP and CFD levels were positively correlated with the occurrence of NPM1 (P=0.048 and P=0.026, respectively). Multifactorial Cox proportional hazards regression model analysis showed that LEP <0.2 ng/mL was an independent risk factor for progression-free survival (PFS) and overall survival in patients with MDS (P=0.002 and P<0.001, respectively), whereas NAMPT <2.1 ng/mL was a protective factor for PFS in patients with MDS (P=0.043).
      Conclusions  Adipocytokines in the bone marrow microenvironment are closely associated with the clinical characteristics, gene mutations, and prognosis of patients with MDS, with LEP <0.2 ng/mL being an independent prognostic risk factor and NAMPT <2.1 ng/mL being a prognostic protective factor.

     

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