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未经化疗的一线利妥昔单抗治疗滤泡性淋巴瘤患者活检的基因表达和拷贝数分析。

Gene expression and copy number profiling of follicular lymphoma biopsies from patients treated with first-line rituximab without chemotherapy.

机构信息

Institute of Pathology, University of Würzburg, Comprehensive Cancer Center Mainfranken, Würzburg, Germany.

Department of Oncology, Oslo University Hospital, Oslo, Norway.

出版信息

Leuk Lymphoma. 2023 Dec;64(12):1927-1937. doi: 10.1080/10428194.2023.2240462. Epub 2023 Sep 8.

Abstract

The Nordic Lymphoma Study Group has performed two randomized clinical trials with chemotherapy-free first-line treatment (rituximab +/- interferon) in follicular lymphoma (FL), with 73% of patients alive and 38% without any need of chemotherapy after 10.6 years median follow-up. In order to identify predictive markers, that may also serve as therapeutic targets, gene expression- and copy number profiles were obtained from 97 FL patients using whole genome microarrays. Copy number alterations (CNAs) were identified, e.g. by GISTIC. Cox Lasso Regression and Lasso logistic regression were used to determine molecular features predictive of time to next therapy (TTNT). A few molecular changes were associated with TTNT (e.g. increased expression of INPP5B, gains in 12q23/q24), but were not significant after adjusting for multiple testing. Our findings suggest that there are no strong determinants of patient outcome with respect to GE data and CNAs in FL patients treated with a chemotherapy-free regimen (i.e. rituximab +/- interferon).

摘要

北欧淋巴瘤研究组(Nordic Lymphoma Study Group)开展了两项滤泡性淋巴瘤(FL)一线无化疗治疗(利妥昔单抗 +/- 干扰素)的随机临床试验,中位随访 10.6 年后,73%的患者存活,38%的患者无需化疗。为了确定可能作为治疗靶点的预测标志物,研究组使用全基因组微阵列对 97 例 FL 患者的基因表达和拷贝数谱进行了分析。通过 GISTIC 等方法确定了拷贝数改变(CNAs)。采用 Cox Lasso 回归和 Lasso 逻辑回归确定了预测下一次治疗时间(TTNT)的分子特征。一些分子变化与 TTNT 相关(例如 INPP5B 表达增加,12q23/q24 获得),但在调整多重检验后无统计学意义。我们的研究结果表明,对于接受无化疗方案(即利妥昔单抗 +/- 干扰素)治疗的 FL 患者,基于基因表达和拷贝数改变的数据,不存在明显的患者预后决定因素。

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