Variability of the metabolomic profiles in terms of potential confounding variables in the four principal components identified by PCA and expressed as F-values together with the corresponding p-values (in brackets).

ANOVA test, significant values (p<0.05) are in bold.
Smoking, co-morbidity, ACPA and RF variables are defined as presence or absence; dietary habits variable is defined as mediterranean diet or non-mediterranean diet; age and disease duration variables are defined as numerical values (number of months); concomitant treatment variable is defined as four groups: glucocorticoids, DMARDs, DMARDs and glucocorticoids and no immunosuppressants.
Among subject-related and disease-related factors, co-morbidity and RF, respectively, affected the clustering of metabolic profiles in terms of a minor likelihood of response to treatment in patients positive for either of them. However, by using Pearson’s simple and partial correlation analysis to simultaneously investigate PCA score, responder or non-responder status, and co-morbidities, the metabolic variations on PC1 were mainly associated with the prediction of response to etanercept.
ACPA: anti-citrullinated protein/peptide antibodies; RF: rheumatoid factor.
Variability of the metabolomic profiles in terms of potential confounding variables in the four principal components identified by PCA and expressed as F-values together with the corresponding p-values (in brackets).

方差分析（ANOVA）检验的显著性数值（p<0.05）以粗体标注。
吸烟史、合并症、抗瓜氨酸化蛋白/肽抗体（ACPA）与类风湿因子（RF）变量均以“存在”或“不存在”赋值；饮食习惯变量分为地中海饮食与非地中海饮食两类；年龄与病程以数值（单位：月）表示；伴随治疗分为四组：糖皮质激素单药、改善病情抗风湿药（DMARDs）单药、糖皮质激素联合改善病情抗风湿药以及无免疫抑制剂治疗。
在受试者相关与疾病相关因素中，合并症与类风湿因子（RF）分别对代谢组学特征的聚类产生影响：二者任意一项呈阳性的患者，其治疗应答概率均相对偏低。此外，本研究通过Pearson简单相关与偏相关分析，同时探究主成分分析（PCA）得分、治疗应答状态与合并症的关联，结果显示PC1轴上的代谢变化主要与依那西普的治疗应答预测相关。
术语注释：ACPA为抗瓜氨酸化蛋白/肽抗体（anti-citrullinated protein/peptide antibodies）；RF为类风湿因子（rheumatoid factor）。
本研究针对通过主成分分析（PCA）识别出的4个主成分，分析其潜在混杂变量对代谢组学特征的影响程度，结果以F值及对应p值（括号内标注）呈现。