Zhao Kewei, Zheng Xin, Liu Xinxiu, Liu Tao, Ke Zhonghe, Zhu Fang, Wen Qiuyue, Xin Beibei, Li Qiuhui, Zhang Liling
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Oncologist. 2024 May 3;29(5):e672-e680. doi: 10.1093/oncolo/oyae008.
Evidence has demonstrated that monitoring of the variable, diversity, and joining gene segments (VDJ) rearrangement of the immunoglobulin (Ig) genes in the circulating tumor DNA (ctDNA) is of value in predicting the outcomes of diffuse large B cell lymphoma (DLBCL). In this study, we investigated the role of VDJ rearrangement proportion in ctDNA for predicting DLBCL progression.
Patients diagnosed with newly diagnosed DLBCL were included in this study. The VDJ sequences of IgH were detected using next-generation sequencing (NGS) in formalin-fixed paraffin-embedded tissue and/or peripheral blood. The clonotype of the highest proportion in the peripheral blood was defined as the "dominant circulating clonotype," whilst the clonotype of the highest proportion in matched tissue that is detected in peripheral blood was defined as the "dominant tissue-matched clonotype." The decision tree, a machine learning-based methodology, was used to establish a progression-predicting model through a combination of "dominant tissue-matched clonotype" proportion or "dominant circulating clonotype" proportion, and the clinicopathological information, including age, sex, cell of origin, stage, international prognostic index, lactate dehydrogenase, number of extranodal involvements and β2-microglobulin.
A total of 55 patients with eligible sequencing data were used for prognosis analysis, among which 36 patients had matched tissue samples. The concordance rate of "dominant circulating clonotype" and "dominant tissue-matched clonotype" was 19.44% (7/36). The decision tree model showed that the combination of extranodal involvement event and "dominant circulating clonotype" proportion (≥37%) had a clinical value in predicting the prognosis of DLBCL following combined chemotherapy (sensitivity, 0.63; specificity, 0.81; positive prediction value (PPV), 0.59; negative prediction value, 0.83; kappa value, 0.42). Noticeably, the combination of the "dominant tissue-matched clonotype" and extranodal involvement event showed a higher value in predicting the progression (sensitivity, 0.85; specificity, 0.78; PPV, 0.69; kappa value, 0.64).
IgH proportion detected in the ctDNA samples traced from tissue samples has a high clinical value in predicting the progression of DLBCL.
有证据表明，监测循环肿瘤DNA（ctDNA）中免疫球蛋白（Ig）基因的可变区、多样性和连接基因片段（VDJ）重排对预测弥漫性大B细胞淋巴瘤（DLBCL）的预后具有重要意义。在本研究中，我们探讨了ctDNA中VDJ重排比例在预测DLBCL进展中的作用。
本研究纳入新诊断的DLBCL患者。使用下一代测序（NGS）检测福尔马林固定石蜡包埋组织和/或外周血中IgH的VDJ序列。外周血中比例最高的克隆型被定义为“主要循环克隆型”，而在外周血中检测到的匹配组织中比例最高的克隆型被定义为“主要组织匹配克隆型”。决策树是一种基于机器学习的方法，通过结合“主要组织匹配克隆型”比例或“主要循环克隆型”比例以及临床病理信息（包括年龄、性别、起源细胞、分期、国际预后指数、乳酸脱氢酶、结外受累数目和β2-微球蛋白）来建立进展预测模型。
共有55例具有合格测序数据的患者用于预后分析，其中36例患者有匹配的组织样本。“主要循环克隆型”与“主要组织匹配克隆型”的一致率为19.44%（7/36）。决策树模型显示，结外受累事件与“主要循环克隆型”比例（≥37%）的组合在预测联合化疗后DLBCL的预后方面具有临床价值（敏感性，0.63；特异性，0.摘要：背景：有证据表明，监测循环肿瘤DNA（ctDNA）中免疫球蛋白（Ig）基因的可变区、多样性和连接基因片段（VDJ）重排对预测弥漫性大B细胞淋巴瘤（DLBCL）的预后具有重要意义。在本研究中，我们探讨了ctDNA中VDJ重排比例在预测DLBCL进展中的作用。
本研究纳入新诊断的DLBCL患者。使用下一代测序（NGS）检测福尔马林固定石蜡包埋组织和/或外周血中IgH的VDJ序列。外周血中比例最高的克隆型被定义为“主要循环克隆型”，而在外周血中检测到的匹配组织中比例最高的克隆型被定义为主要组织匹配克隆型。决策树是一种基于机器学习的方法，通过结合主要组织匹配克隆型比例或主要循环克隆型比例以及临床病理信息（包括年龄、性别、起源细胞、分期、国际预后指数、乳酸脱氢酶、结外受累数目和β2-微球蛋白）来建立进展预测模型。
共有55例具有合格测序数据的患者用于预后分析，其中36例患者有匹配的组织样本。主要循环克隆型与主要组织匹配克隆型的一致率为19.44%（7/36）。决策树模型显示，结外受累事件与主要循环克隆型比例（≥37%）的组合在预测联合化疗后DLBCL的预后方面具有临床价值（敏感性，0.63；特异性，0.81；阳性预测值（PPV），0.59；阴性预测值，0.83；kappa值，0.42）。值得注意的是，主要组织匹配克隆型与结外受累事件的组合在预测进展方面具有更高的价值（敏感性，0.85；特异性，0.78；PPV，0.69；kappa值，0.64）。
从组织样本追溯的ctDNA样本中检测到的IgH比例在预测DLBCL进展方面具有较高的临床价值。
81；阳性预测值（PPV），0.59；阴性预测值，0.83；kappa值，0.42）。值得注意的是，“主要组织匹配克隆型”与结外受累事件的组合在预测进展方面具有更高的价值（敏感性，0.85；特异性，0.78；PPV，0.69；kappa值，0.64）。
从组织样本追溯得到的ctDNA样本中检测到的IgH比例在预测DLBCL进展方面具有较高的临床价值。
