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临床定义的高级别浆液性卵巢癌治疗亚组的独特T细胞受体库多样性

Distinct T cell receptor repertoire diversity of clinically defined high-grade serous ovarian cancer treatment subgroups.

作者信息

Lee Sanghoon, Zhao Li, Little Latasha D, Westin Shannon N, Jazarei Amir A, Fleming Nicole D, Zhang Jianhua, Futreal P Andrew, Sood Anil K

机构信息

Department of Systems Biology, The University of Texas MD Anderson Cancer Center, 1881 East Road, Unit 1908, Houston, TX, USA.

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

出版信息

iScience. 2021 Jan 9;24(2):102053. doi: 10.1016/j.isci.2021.102053. eCollection 2021 Feb 19.

Abstract

In patients with high-grade serous ovarian cancer (HGSC), it is unclear which genomic features are related to complete gross resection (R0), which is typically associated with better clinical outcomes, or response to neoadjuvant chemotherapy (NACT). In this study, we evaluated T cell receptor (TCR) repertoire diversity in primary and metastatic tumor samples (n = 90) from clinically well-annotated patients with HGSC who achieved R0 or received NACT with excellent or poor response based on a laparoscopic triage algorithm. TCR sequencing followed by an integrative analysis with comprehensive multi-omics data identified higher TCR diversity (e.g., higher number of unique productive sequences and less clonal relatedness) in the R0 than NACT groups. We found enrichment of specific genes usage, distinct mutual exclusiveness and co-occurrence pattern of genes among the groups. We also found significantly positive correlations between clonal relatedness and neoantigens, copy number variations, and mutation load in the groups.

摘要

在高级别浆液性卵巢癌(HGSC)患者中,目前尚不清楚哪些基因组特征与完全肿瘤全切除(R0)相关,而R0通常与更好的临床结果相关,也不清楚这些特征与新辅助化疗(NACT)的反应有何关联。在本研究中,我们评估了来自临床注释良好的HGSC患者的原发和转移肿瘤样本(n = 90)中的T细胞受体(TCR)库多样性,这些患者实现了R0,或根据腹腔镜分诊算法接受了反应良好或不良的NACT。TCR测序,随后与综合多组学数据进行综合分析,结果显示R0组的TCR多样性高于NACT组(例如,独特的有效序列数量更多,克隆相关性更低)。我们发现了特定基因使用的富集、组间基因独特的互斥性和共现模式。我们还发现,组内克隆相关性与新抗原、拷贝数变异和突变负荷之间存在显著正相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40f0/7840469/0c8ad39a1141/fx1.jpg

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