Machine learning predicts stem cell transplant response in severe scleroderma.
Machine learning predicts stem cell transplant response in severe scleroderma.
复制标题
DOI：
10.1136/annrheumdis-2020-217033
复制
发表时间：
2020-12
影响因子：
27.4
通讯作者：
Whitfield ML
中科院分区：
文献类型：
--
作者：
Franks JM;Martyanov V;Wang Y;Wood TA;Pinckney A;Crofford LJ;Keyes-Elstein L;Furst DE;Goldmuntz E;Mayes MD;McSweeney P;Nash RA;Sullivan KM;Whitfield ML
硬皮病：环磷酰胺或移植(SCOT)试验显示，与环磷酰胺(CYC)相比，造血干细胞移植(HSCT)具有临床益处。我们将SCOT临床试验中的PBC(外周血细胞)样本映射到硬皮病固有亚群，并测试了它们预测HSCT长期应答的假设。我们分析了SCOT参与者外周血中的基因表达，以确定不同的治疗反应。63名SCOT参与者在基线和随访时间点产生了PBC基因表达数据。完成治疗方案的参与者根据基线时内在基因表达亚组进行分层，评估无事件生存(EFS)，并分析差异表达基因(DEG)。接受造血干细胞移植的纤维增殖组的参与者与接受环磷酰胺移植的纤维增殖组的参与者相比，其EFS有显著改善(p=0.0091)。相反，对于来自正常亚组(p=0.77)或炎症亚组(p=0.1)的参与者，CyC组和HSCT组的EFS没有显著差异。在每个时间点，我们观察到，与使用HSCT的CyC组相比，HSCT组的DEG更多，显示出免疫反应途径的显著变化。与环磷酰胺相比，来自纤维增生性亚组的参与者显示出从HSCT中获得最显著的长期益处。这项研究表明，患者的内在亚组分层可用于识别从HSCT中获得显著好处的SSc患者。
The Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial demonstrated clinical benefit of haematopoietic stem cell transplant (HSCT) compared with cyclophosphamide (CYC). We mapped PBC (peripheral blood cell) samples from the SCOT clinical trial to scleroderma intrinsic subsets and tested the hypothesis that they predict long-term response to HSCT. We analysed gene expression from PBCs of SCOT participants to identify differential treatment response. PBC gene expression data were generated from 63 SCOT participants at baseline and follow-up timepoints. Participants who completed treatment protocol were stratified by intrinsic gene expression subsets at baseline, evaluated for event-free survival (EFS) and analysed for differentially expressed genes (DEGs). Participants from the fibroproliferative subset on HSCT experienced significant improvement in EFS compared with fibroproliferative participants on CYC (p=0.0091). In contrast, EFS did not significantly differ between CYC and HSCT arms for the participants from the normal-like subset (p=0.77) or the inflammatory subset (p=0.1). At each timepoint, we observed considerably more DEGs in HSCT arm compared with CYC arm with HSCT arm showing significant changes in immune response pathways. Participants from the fibroproliferative subset showed the most significant long-term benefit from HSCT compared with CYC. This study suggests that intrinsic subset stratification of patients may be used to identify patients with SSc who receive significant benefit from HSCT.
登录
查看更多内容
WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
6.5
作者：
Pendergrass, Sarah A.;Lemaire, Raphael;Francis, Ian P.;Mahoney, J. Matthew;Lafyatis, Robert;Whitfield, Michael L.
通讯作者：
Whitfield, Michael L.
DOI：
10.1016/j.jid.2018.01.006
发表时间：
2018-06
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Hinchcliff M;Toledo DM;Taroni JN;Wood TA;Franks JM;Ball MS;Hoffmann A;Amin SM;Tan AU;Tom K;Nesbeth Y;Lee J;Ma M;Aren K;Carns MA;Pioli PA;Whitfield ML
通讯作者：
Whitfield ML
DOI：
10.1002/art.40358
发表时间：
2018-03
期刊：
Arthritis & rheumatology (Hoboken, N.J.)
影响因子：
--
作者：
Gordon JK;Martyanov V;Franks JM;Bernstein EJ;Szymonifka J;Magro C;Wildman HF;Wood TA;Whitfield ML;Spiera RF
通讯作者：
Spiera RF
DOI：
10.1073/pnas.091062498
发表时间：
2001-04-24
影响因子：
11.1
作者：
Tusher, VG;Tibshirani, R;Chu, G
通讯作者：
Chu, G