Pretreatment circulating serum cytokines associated with follicular and diffuse large B-cell lymphoma: a clinic-based case-control study.
Pretreatment circulating serum cytokines associated with follicular and diffuse large B-cell lymphoma: a clinic-based case-control study.
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DOI：
10.1016/j.cyto.2012.08.028
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发表时间：
2012-12
期刊：
影响因子：
3.8
通讯作者：
Novak, Anne J.
中科院分区：
文献类型：
--
作者：
Charbonneau, Bridget;Maurer, Matthew J.;Ansell, Stephen M.;Slager, Susan L.;Fredericksen, Zachary S.;Ziesmer, Steven C.;Macon, William R.;Habermann, Thomas M.;Witzig, Thomas E.;Link, Brian K.;Cerhan, James R.;Novak, Anne J.
免疫功能异常是非霍奇金淋巴瘤（NHL）易感性的关键因素。我们评估了30种细胞因子与弥漫性大B细胞（DLBCL）和滤泡性（FL）淋巴瘤的相关性。我们在一项234例FL、188例DLBCL和400例对照受试者的病例对照研究中，使用多重测定法测量治疗前血清中30种细胞因子的浓度。非条件Logistic回归用于估计经年龄和性别校正的比值比（OR）和95%置信区间（CI），多分类回归用于评估FL和DLBCL之间的异质性。主成分分析（PCA）用于评估与FL和DLBCL相关的细胞因子谱。在单一细胞因子模型中，我们发现30种循环血清细胞因子中有12种与FL和/或DLBCL显着相关（P<0.05），经过多次测试（q<0.05）。可溶性IL-2 R（sIL-2 R）与FL（最高与最低三分位数的OR=6.0，95% CI 3.8-9.5; p-trend=1.8 × 10−21）和DLBCL（OR=7.6，95% CI 4.5-13.1; p-trend=7.2 × 10−20）的相关性最强。IL 1 RA和IL-12 p40也显示出与DLBCL和FL相似的相关性。相比之下，HGF、IFN-γ和MIP-1α与DLBCL的相关性比FL更强，而IL-6、IL-8、IL-10、IFN-γ、IP-10和VEGF仅在考虑多重检验后与DLBCL有统计学显著相关。然而，在PCA建模中，基于sIL-2 R、IL-1 RA、MIG、IP-10、IL-8和IL-12 p40的细胞因子谱解释了对照组与FL和DLBCL之间的大部分变异性。我们确定了DLBCL特有的一些单一细胞因子，但总体细胞因子相关性更相似，而不是DLBCL和FL的不同。虽然这些数据受到反向因果关系的限制，但它们确实表明细胞因子和细胞因子谱可以在未来的研究中优先考虑。
Abnormal immune function is a key factor in predisposition to non-Hodgkin lymphoma (NHL). We evaluated the association of 30 cytokines individually and as a profile with diffuse large B-cell (DLBCL) and follicular (FL) lymphomas. We used a multiplexed assay to measure 30 cytokine concentrations in pre-treatment serum in a case-control study of 234 FL, 188 DLBCL, and 400 control participants. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) adjusted for age and sex, and polytomous regression was used to evaluate heterogeneity between FL and DLBCL. Principal components analysis (PCA) was used to assess cytokine profiles associated with FL and DLBCL. In single cytokine modeling, we found that 12 of the 30 circulating serum cytokines were significantly (P<0.05) associated with FL and/or DLBCL after accounting for multiple testing (q<0.05). Soluble IL-2R (sIL-2R) had the strongest association with both FL (OR=6.0 for highest versus lowest tertile, 95% CI 3.8–9.5; p-trend=1.8 × 10−21) and DLBCL (OR=7.6, 95% CI 4.5–13.1; p-trend=7.2 × 10−20). IL1RA and IL-12p40 also showed similar associations for DLBCL and FL. In contrast, HGF, MIG, and MIP-1α had a stronger association with DLBCL compared to FL, and IL-6, IL-8, IL-10, IFN-γ, IP-10, and VEGF were only statistically significantly associated with DLBCL after accounting for multiple testing. However, in PCA modeling, a cytokine profile based on sIL-2R, IL-1RA, MIG, IP-10, IL-8, and IL-12p40 explained most of the variability between controls and both FL and DLBCL. We identified some single cytokines unique to DLBCL, but overall cytokine associations were more similar than distinct for DLBCL and FL. While these data are limited by concerns of reverse causality, they do suggest cytokines and cytokine profiles that can be prioritized in future studies.
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