背景:癌症恶病质是一种临床疾病,其特征是可识别的“疾病行为”,并伴有瘦身体组织的丧失。全球营养不良领导(GLIM)提出了表型(无意减肥,低体重指数和低肌肉质量)和病因(减少食物摄入和炎症或疾病负担)诊断标准。最近的工作表明血清乳酸脱氢酶(LDH)可能代表第三种病因标准。人们对它与GLIM的关系知之甚少。对其比较预后价值和相关性进行了系统评价和荟萃分析。
方法:搜索电子数据库(PubMed,Medline,奥维德,Cochrane)截至2023年2月,用于鉴定比较LDH和GLIM标准在癌症中的预后价值的研究。在有此数据的情况下,对LDH与GLIM成分之间的关系进行了分析。RevMan5.4.1用于对每个诊断标准进行荟萃分析,这些诊断标准有3项或更多项研究,这些研究报告了总生存期(OS)的95%置信区间的风险比。
结果:共纳入119项研究。晚期肺癌是研究最多的人群。荟萃分析包括6项关于LDH和体重减轻的研究(n=2,165),关于LDH和低BMI的17项研究(n=7,540),关于LDH和低肌肉质量的5项研究(n=758),0项关于LDH和食物摄入的研究和97项关于LDH和炎症的研究(n=37,185)。血清LDH升高与低BMI之间存在显着关联(OR1.39,1.09-1.77;p=0.008),NLR升高(OR2.04,1.57-2.65;p<0.00001)和CRP升高(OR2.58,1.81-3.67;p<0.00001)。血清LDH升高与肌肉质量降低之间没有关联。只有一项研究提供了有关LDH与意外体重减轻之间关联的数据。LDH升高显示出与意外体重减轻(HR1.57,1.23-1.99;p=0.0002)相比的OS(HR1.86,1.60-2.16;p<0.00001),并且OS(HR2.01,1.73-2.34;p<0.00001)与低BMI(HR1.57,1.29-2.90;p<0.0001)相似。LDH还显示出OS(HR2.25,1.76-2.87;p<0.00001)与低肌肉质量(HR1.93,1.14-3.27;p=0.01)一致,LDH作为NLR升高(HR1.57,1.44-1.71;p<0.00001)或CRP(HR1.53,1.41-1.65;p<0.00001)的OS差(HR1.71,1.60-1.82;p<0.00001)。
结论:目前的文献表明血清LDH升高与癌症的炎症相关(病因GLIM标准),然而,需要更多的工作来建立LDH与GLIM表型成分之间的关系。此外,与GLIM标准相比,血清LDH升高似乎是癌症总生存期的比较预后指标.
BACKGROUND: Cancer cachexia is a clinical condition characterized by recognizable \"sickness behaviors\" accompanied by loss of lean body tissue. The Global Leadership on Malnutrition (GLIM) has proposed phenotypic (unintentional weight loss, low body mass index and low muscle mass) and aetiologic (reduced food intake and inflammation or disease burden) diagnostic criteria. Recent work has suggested serum lactate dehydrogenase (LDH) might represent a 3rd aetiologic criteria. Little is known of its relationship with GLIM. A systematic
review and meta-analysis of their comparative prognostic value and association was performed.
METHODS: A search of electronic databases (PubMed, Medline, Ovid, Cochrane) up to February 2023 was used to identify studies that compared the prognostic value of LDH and components of the GLIM criteria in cancer. An analysis of the relationship between LDH and the components of GLIM was undertaken where this data was available. RevMan 5.4.1 was used to perform a meta-analysis for each diagnostic criteria that had 3 or more studies which reported hazard ratios with a 95 per cent confidence interval for overall survival (OS).
RESULTS: A total of 119 studies were reviewed. Advanced lung cancer was the most studied population. Included in the meta-analysis were 6 studies (n=2165) on LDH and weight loss, 17 studies (n=7540) on LDH and low BMI, 5 studies (n=758) on LDH and low muscle mass, 0 studies on LDH and food intake and 93 studies (n=32,190) on LDH and inflammation. There was a significant association between elevated serum LDH and each of low BMI (OR 1.39, 1.09 - 1.77; p=0.008), elevated NLR (OR 2.04, 1.57 - 2.65; p<0.00001) and elevated CRP (OR 2.58, 1.81 - 3.67; p<0.00001). There was no association between elevated serum LDH and low muscle mass. Only one study presented data on the association between LDH and unintentional weight loss. Elevated LDH showed a comparative OS (HR 1.86, 1.57 - 2.07; p<0.00001) to unintentional weight loss (HR 1.57, 1.23 - 1.99; p=0.0002) and had a similar OS (HR 2.00, 1.70 - 2.34; p<0.00001) to low BMI (HR 1.57, 1.29-2.90; p<0.0001). LDH also showed an OS (HR 2.25, 1.76 - 2.87; p<0.00001) congruous with low muscle mass (HR 1.93, 1.14 - 3.27; p=0.01) and again, LDH conferred as poor an OS (HR 1.77, 1.64-1.90; p<0.00001) as elevated NLR (HR 1.61, 1.48 - 1.77; p<0.00001) or CRP (HR 1.55, 1.43 - 1.69; p<0.00001).
CONCLUSIONS: Current literature suggests elevated serum LDH is associated with inflammation in cancer (an aetiologic GLIM criterion), however more work is required to establish the relationship between LDH and the phenotypic components of GLIM. Additionally, elevated serum LDH appears to be a comparative prognosticator of overall survival in cancer when compared to the GLIM criteria.