作为生物医学领域的科学家，我精通英语和简体中文。将以下段落准确地翻译成简体中文，并符合学术论文的语言规范和原始陈述结构。 TP53变异等位基因频率低作为肺腺癌抗程序性死亡（配体）1单独治疗的生物标记物。
Low TP53 variant allele frequency as a biomarker for anti-programmed death (ligand) 1 monotherapy in lung adenocarcinoma.
发表日期：2023 Aug 04
作者：
Shouzheng Wang, Tongji Xie, Yan Li, Lei Guo, Jianming Ying, Yan Wang, Xuezhi Hao, Xingyuan Wang, Junling Li, Puyuan Xing
来源：
CANCER
摘要：
在应用TP53作为肺腺癌（LUAD）中PD-(L)1单药治疗的预测生物标志物时，应考虑TP53突变的异质性。然而，是否应考虑TP53变体等位基因频率（VAF）仍然未知。将发表的研究和本地队列中的LUAD患者纳入其中，以发现和验证TP53 VAF与PD-(L)1抑制剂疗效之间的关系。癌症基因组图谱（TCGA）LUAD数据包含了基因组学、转录组学和肿瘤微环境分析。在发现队列的159名患者中，低TP53 VAF患者（VAF ≤ 25%）的无进展生存期（PFS）明显长于高TP53 VAF（5.4 vs. 3.3 月；p = .021）和TP53野生型患者（5.4 vs. 2.5 月；p = .011）。多变量Cox回归分析表明低TP53 VAF是较好疗效的独立生物标志物。在合并验证队列的50名患者中，低TP53 VAF患者的中位PFS也显著长于高TP53 VAF患者（12.0 vs. 2.1 月；p = .037）。通过对469个TCGA LUAD样本进行分析，发现低TP53 VAF与显著更高的PD-L1表达、与T细胞激活、T细胞介导的免疫以及干扰素-γ信号通路相关的基因集富集，与高TP53 VAF和TP53野生型相比，与更多肿瘤浸润的CD8+ T细胞相关。当使用TP53作为预测生物标志物时，还应考虑TP53 VAF。只有低TP53 VAF与抗PD-(L)1单药疗法的较好疗效独立相关，这可能是由于更高的PD-L1表达和更多肿瘤浸润的CD8+ T细胞。© 2023 American Cancer Society.
TP53 mutation heterogeneity should be considered when using TP53 as a predictive biomarker for anti-programmed death (ligand) 1 (PD-(L)1) monotherapy in lung adenocarcinoma (LUAD). However, whether TP53 variant allele frequency (VAF) should also be considered remains unknown.Patients with LUAD from both published research and the local cohort were included to discover and validate the relationship between TP53 VAF and the efficacy of PD-(L)1 inhibitors. The Cancer Genome Atlas (TCGA) LUAD data were included for genomic, transcriptomic, and tumor microenvironment analysis.Among 159 patients in the discovery cohort, low TP53 VAF patients (VAF ≤ 25%) experienced significantly longer progression-free survival (PFS) than both high TP53 VAF (5.4 vs. 3.3 months; p = .021) and TP53-wild-type patients (5.4 vs. 2.5 months; p = .011). Multivariate Cox regression revealed low TP53 VAF as an independent biomarker of better efficacy. Among 50 patients in the combined validation cohort, median PFS of low TP53 VAF patients was also significantly longer than that of high TP53 VAF patients (12.0 vs. 2.1 months; p = .037). Analyzed with 469 TCGA LUAD samples, low TP53 VAF is associated with significantly higher PD-L1 expression, enrichment of gene sets related to T-cell activation, T cell-mediated immunity, and interferon-γ signaling pathways, and independently associated with more tumor-infiltrating CD8+ T cells compared with both high TP53 VAF and TP53-wild type.TP53 VAF should also be considered when using TP53 as a predictive biomarker. Only low TP53 VAF is independently associated with better efficacy of anti-PD-(L)1 monotherapy, which may result from higher PD-L1 expression and more tumor-infiltrating CD8+ T cells.© 2023 American Cancer Society.