转录组
肿瘤科
弥漫性大B细胞淋巴瘤
切碎
内科学
疾病
淋巴瘤
医学
基因
生物信息学
生物
基因表达
遗传学
作者
Weicheng Ren,Hui Wan,Sulaf Abd Own,Mattias Berglund,Linyu Li,Mingyu Yang,Xiaobo Li,Dongbing Liu,Xiaofei Ye,Kristina Sonnevi,Gunilla Enblad,Rose‐Marie Amini,Birgitta Sander,Kui Wu,Huilai Zhang,Björn E. Wahlin,Karin E. Smedby,Qiang Pan‐Hammarström
出处
期刊:Leukemia
[Springer Nature]
日期:2023-12-29
标识
DOI:10.1038/s41375-023-02120-7
摘要
Abstract Despite the improvements in clinical outcomes for DLBCL, a significant proportion of patients still face challenges with refractory/relapsed (R/R) disease after receiving first-line R-CHOP treatment. To further elucidate the underlying mechanism of R/R disease and to develop methods for identifying patients at risk of early disease progression, we integrated clinical, genetic and transcriptomic data derived from 2805 R-CHOP-treated patients from seven independent cohorts. Among these, 887 patients exhibited R/R disease within two years (poor outcome), and 1918 patients remained in remission at two years (good outcome). Our analysis identified four preferentially mutated genes ( TP53, MYD88, SPEN, MYC ) in the untreated (diagnostic) tumor samples from patients with poor outcomes. Furthermore, transcriptomic analysis revealed a distinct gene expression pattern linked to poor outcomes, affecting pathways involved in cell adhesion/migration, T-cell activation/regulation, PI3K, and NF-κB signaling. Moreover, we developed and validated a 24-gene expression score as an independent prognostic predictor for treatment outcomes. This score also demonstrated efficacy in further stratifying high-risk patients when integrated with existing genetic or cell-of-origin subtypes, including the unclassified cases in these models. Finally, based on these findings, we developed an online analysis tool ( https://lymphprog.serve.scilifelab.se/app/lymphprog ) that can be used for prognostic prediction for DLBCL patients.
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