Prognostic relevance of HRDness gene expression signature in ovarian high-grade serous carcinoma; JGOG3025-TR2 study
Prognostic relevance of HRDness gene expression signature in ovarian high-grade serous carcinoma; JGOG3025-TR2 study
复制标题
HRDness 基因表达特征在卵巢高级别浆液性癌中的预后相关性；
DOI：
10.1038/s41416-022-02122-9
复制
发表时间：
2023
影响因子：
8.8
通讯作者：
Matsumura Noriomi
中科院分区：
文献类型：
--
作者：
Takamatsu Shiro;Yoshihara Kosuke;Baba Tsukasa;Shimada Muneaki;Yoshida Hiroshi;Kajiyama Hiroaki;Oda Katsutoshi;Mandai Masaki;Okamoto Aikou;Enomoto Takayuki;Matsumura Noriomi
背景本研究旨在评估卵巢高级别浆液性癌(HGSC)中同源重组修复途径缺陷(HRD)。方法在癌症基因组图谱的卵巢癌数据中，我们鉴定了在有和没有HRD基因组瘢痕的肿瘤之间差异表达的基因，并将这些基因命名为HRDness Signature。我们对274个HGSC肿瘤进行了SNP阵列、RNA测序和甲基化阵列分析，其中有51个基因的靶向测序和临床数据可用来生成JGOG3025-TR2数据集。通过计算评分和机器学习预测，在包括JGOG3025-TR2队列在内的外部数据集上测试了高HRDness签名。结果高分和积极预测的高HRDness签名与BRCA改变、基因组疤痕评分和更好的生存显著相关。另一方面，在高得分和/或阳性预测的病例中，那些BRCA1甲基化的患者显示出较差的存活率。在JGOG3025-TR2队列中，HRD状态与复发后使用奥拉帕利以及开始治疗后无进展生存显著相关。结论HRDness基因表达特征与预后良好相关，而BRCA1甲基化与预后不良相关。新生成的JGOG3025-TR2数据集将在未来的HGSC研究中有用。
BackgroundThis study aimed to evaluate the homologous recombination repair pathway deficiency (HRD) in ovarian high-grade serous carcinoma (HGSC).MethodsIn the ovarian cancer data from The Cancer Genome Atlas, we identified genes differentially expressed between tumours with and without HRD genomic scars and named these genes “HRDness signature”. We performed SNP array, RNA sequencing, and methylation array analyses on 274 HGSC tumours for which targeted sequencing of 51 genes and clinical data were available to generate JGOG3025-TR2 dataset. The HRDness signature was tested on external datasets, including the JGOG3025-TR2 cohort, by computational scoring and machine-learning prediction.ResultsHigh scores and positive predictions of the HRDness signature were significantly associated withBRCAalterations, genomic scar scores, and better survival. On the other hand, among cases with high scores and/or positive predictions, those withBRCA1 methylation showed poorer survival. In the JGOG3025-TR2 cohort, HRD status was significantly associated with the use of olaparib after relapse and progression-free survival after its initiation.ConclusionsThe HRDness gene expression signature is associated with a good prognosis, whileBRCA1methylation is associated with a poor prognosis. The newly generated JGOG3025-TR2 dataset will be useful in future HGSC studies.
登录
查看更多内容
影响因子：
28.2
作者：
Birkbak NJ;Wang ZC;Kim JY;Eklund AC;Li Q;Tian R;Bowman-Colin C;Li Y;Greene-Colozzi A;Iglehart JD;Tung N;Ryan PD;Garber JE;Silver DP;Szallasi Z;Richardson AL
通讯作者：
Richardson AL
影响因子：
64.8
作者：
Patch, Ann-Marie;Christie, Elizabeth L.;Bowtell, David D. L.
通讯作者：
Bowtell, David D. L.
影响因子：
--
作者：
Prieske K;Prieske S;Joosse SA;Trillsch F;Grimm D;Burandt E;Mahner S;Schmalfeldt B;Milde-Langosch K;Oliveira-Ferrer L;Woelber L
通讯作者：
Woelber L
影响因子：
15.9
作者：
Verhaak, Roel G. W.;Tamayo, Pablo;Meyerson, Matthew
通讯作者：
Meyerson, Matthew
影响因子：
28.2
作者：
Konstantinopoulos PA;Ceccaldi R;Shapiro GI;D'Andrea AD
通讯作者：
D'Andrea AD