ITPKB突变变异等位基因频率对弥漫性大B细胞淋巴瘤的预后预测价值

张玲珑; 漆小龙; 寇珍; 热那古力·阿不来提; 聂玉玲; 木合拜尔·阿布都尔; 翟顺生; 安利; 毛敏; 李燕

doi:10.3971/j.issn.1000-8578.2023.23.0520

ITPKB突变变异等位基因频率对弥漫性大B细胞淋巴瘤的预后预测价值

Prognostic Predictive Value of ITPKB Mutation's Variant Allele Frequency in Diffuse Large B-cell Lymphoma

摘要

摘要:
目的探讨弥漫性大B细胞淋巴瘤（DLBCL）ITPKB突变变异等位基因频率（VAF）与预后的相关性。
方法纳入2014年6月—2020年12月在新疆维吾尔自治区人民医院初次诊断的155例DLBCL患者，获取石蜡包埋的肿瘤组织标本。提取肿瘤组织DNA，应用二代测序技术检测包括ITPKB在内的475种热点基因，分析高频突变基因VAF与无进展生存（PFS）和总生存（OS）的关系。
结果 ITPKB的突变频率为18.71%，ITPKB突变患者的PFS较未突变患者的PFS明显缩短，但差异无统计学意义（37.00 vs. 108.00个月；HR=1.643, 95%CI: 0.920~2.934, P=0.093）。通过基于R语言的网页工具探寻可区分患者预后的最佳VAF截断值，将患者依据VAF值分成对应的两组（高VAF组 vs. 低VAF+野生型组），ITPKB最佳VAF的截断值为27.48%（HR=3.48, 95%CI: 1.70~7.13, P=0.00027），纳入年龄、性别、COO分型、IPI、LDH等临床指标行多因素Cox分析，结果显示PFS与高ITPKB VAF（≥28%）相关（HR=3.592, 95%CI: 1.738~7.425, P < 0.001），是PFS独立的不良预测因素。
结论 ITPKB突变高负荷为DLBCL患者PFS的独立危险因素，ITPKB突变的VAF在DLBCL患者中具有预后预测价值。

Abstract:
Objective To investigate the correlation between ITPKB mutation's variant allele frequency (VAF) and prognosis of diffuse large B-cell lymphoma (DLBCL).
Methods This study included 155 patients with DLBCL initially diagnosed in the People's Hospital of Xinjiang Uygur Autonomous Region from June 2014 to December 2020. Paraffin-embedded tumor tissue specimens were obtained, and tumor tissue DNA was extracted. A total of 475 hotspot genes including ITPKB were detected by the next generation sequencing to analyze the relationship of the VAF of high-frequency mutant gene with progression-free survival (PFS) and overall survival (OS).
Results The mutation frequency of ITPKB was 18.71%. The PFS was significantly shorter in the patients with ITPKB mutations than in those without mutations (37 months vs. 108 months; HR=1.643, 95%CI: 0.920-2.934, P=0.093). The R-language based web tool was used to find the best VAF cutoff to differentiate prognosis. The patients were divided into two groups (VAF High vs. VAF Low+Wt) according to their VAF values. The optimal VAF threshold for ITPKB was 27.48% (HR=3.480, 95%CI: 1.70-7.13, P=0.00027). Multivariate Cox analysis was conducted using clinical indicators such as age, gender, COO classification, IPI, and LDH, and the results showed that PFS was associated with high ITPKB VAF (≥28%) (HR=3.592, 95%CI: 1.738-7.425, P < 0.001) which was an independent adverse predictor of PFS.
Conclusion The high load of ITPKB mutation is an independent risk factor for the PFS of patients with DLBCL, and the VAF of ITPKB mutation has a prognostic predictive value for patients with DLBCL.

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