TMBcat: A multi-endpoint p-value criterion on different discrepancy metrics for superiorly inferring tumor mutation burden thresholds.
TMBcat: A multi-endpoint p-value criterion on different discrepancy metrics for superiorly inferring tumor mutation burden thresholds.
复制标题
TMBCAT：在不同差异指标上的多点P值标准，用于上推断肿瘤突变负担阈值。
DOI：
10.3389/fimmu.2022.995180
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发表时间：
2022
影响因子：
7.3
通讯作者：
Fang, Wenfeng
中科院分区：
文献类型：
--
作者：
Wang, Yixuan;Lai, Xin;Wang, Jiayin;Xu, Ying;Zhang, Xuanping;Zhu, Xiaoyan;Liu, Yuqian;Shao, Yang;Zhang, Li;Fang, Wenfeng
关键词：
肿瘤突变负荷（TMB）是一种被广泛认可的用于预测免疫治疗疗效的分层生物标志物;然而，由于疗效的多面性和TMB测量的不精确性，分类阈值的数量和通用定义仍然存在争议。我们从区分综合治疗优势的角度提出了一个最小联合p值标准，称为TMBcat，优化了不同癌症队列的TMB分类，并超过了已知的基准。统计框架适用于多维端点，并对TMB测量误差具有容错性。为了探讨TMB与各种免疫治疗结果之间的关系，我们对78例接受抗PD-（L）1治疗的非小细胞肺癌患者和64例鼻咽癌患者进行了回顾性分析。TMBcat的分层结果证实了TMB和免疫治疗之间的关系是非线性的，即，治疗收益并不随TMB的增加而增加，而且这种模式在不同的癌中也不同。因此，多个TMB分类阈值可以灵活地区分患者的预后。这些发现在来自11项已发表研究的943例患者的集合队列中得到进一步验证。总之，我们的工作提出了一个通用的标准和一个可访问的软件包，它们一起，使最佳TMB分组。我们的研究有可能为患者的治疗选择和治疗策略提供创新的见解。
Tumor mutation burden (TMB) is a widely recognized stratification biomarker for predicting the efficacy of immunotherapy; however, the number and universal definition of the categorizing thresholds remain debatable due to the multifaceted nature of efficacy and the imprecision of TMB measurements. We proposed a minimal joint p-value criterion from the perspective of differentiating the comprehensive therapeutic advantages, termed TMBcat, optimized TMB categorization across distinct cancer cohorts and surpassed known benchmarks. The statistical framework applies to multidimensional endpoints and is fault-tolerant to TMB measurement errors. To explore the association between TMB and various immunotherapy outcomes, we performed a retrospective analysis on 78 patients with non-small cell lung cancer and 64 patients with nasopharyngeal carcinomas who underwent anti-PD-(L)1 therapy. The stratification results of TMBcat confirmed that the relationship between TMB and immunotherapy is non-linear, i.e., treatment gains do not inherently increase with higher TMB, and the pattern varies across carcinomas. Thus, multiple TMB classification thresholds could distinguish patient prognosis flexibly. These findings were further validated in an assembled cohort of 943 patients obtained from 11 published studies. In conclusion, our work presents a general criterion and an accessible software package; together, they enable optimal TMB subgrouping. Our study has the potential to yield innovative insights into therapeutic selection and treatment strategies for patients.
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影响因子：
50.3
作者：
Hellmann MD;Callahan MK;Awad MM;Calvo E;Ascierto PA;Atmaca A;Rizvi NA;Hirsch FR;Selvaggi G;Szustakowski JD;Sasson A;Golhar R;Vitazka P;Chang H;Geese WJ;Antonia SJ
通讯作者：
Antonia SJ
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
DOI：
10.1038/nrc3239
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Pardoll DM
通讯作者：
Pardoll DM
影响因子：
30.8
作者：
Miao D;Margolis CA;Vokes NI;Liu D;Taylor-Weiner A;Wankowicz SM;Adeegbe D;Keliher D;Schilling B;Tracy A;Manos M;Chau NG;Hanna GJ;Polak P;Rodig SJ;Signoretti S;Sholl LM;Engelman JA;Getz G;Jänne PA;Haddad RI;Choueiri TK;Barbie DA;Haq R;Awad MM;Schadendorf D;Hodi FS;Bellmunt J;Wong KK;Hammerman P;Van Allen EM
通讯作者：
Van Allen EM
影响因子：
4.5
作者：
Hashim, Mahmoud;Pfeiffer, Boris M.;Heeg, Bart
通讯作者：
Heeg, Bart