دورية أكاديمية
Homologous recombination deficiency (HRD) can predict the therapeutic outcomes of immuno-neoadjuvant therapy in NSCLC patients
| العنوان: | Homologous recombination deficiency (HRD) can predict the therapeutic outcomes of immuno-neoadjuvant therapy in NSCLC patients |
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| المؤلفون: | Zhen Zhou, Zhengping Ding, Jie Yuan, Shengping Shen, Hong Jian, Qiang Tan, Yunhai Yang, Zhiwei Chen, Qingquan Luo, Xinghua Cheng, Yongfeng Yu, Xiaomin Niu, Liqiang Qian, Xiaoke Chen, Linping Gu, Ruijun Liu, Shenglin Ma, Jia Huang, Tianxiang Chen, Ziming Li, Wenxiang Ji, Liwei Song, Lan Shen, Long Jiang, Zicheng Yu, Chao Zhang, Zaixian Tai, Changxi Wang, Rongrong Chen, David P. Carbone, Xuefeng Xia, Shun Lu |
| المصدر: | Journal of Hematology & Oncology, Vol 15, Iss 1, Pp 1-6 (2022) |
| بيانات النشر: | BMC, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Diseases of the blood and blood-forming organs LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | Whole-exome sequencing, Homologous recombination deficiency, Neoadjuvant immunotherapy, NSCLC, Biomarker, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | Abstract Background Neoadjuvant immunotherapy is emerging as novel effective intervention in lung cancer, but study to unearth effective surrogates indicating its therapeutic outcomes is limited. We investigated the genetic changes between non-small cell lung cancer (NSCLC) patients with varied response to neoadjuvant immunotherapy and discovered highly potential biomarkers with indicative capability in predicting outcomes. Methods In this study, 3 adenocarcinoma and 11 squamous cell carcinoma NSCLC patients were treated by neoadjuvant immunotherapy with variated regimens followed by surgical resection. Treatment-naive FFPE or fresh tissues and blood samples were subjected to whole-exome sequencing (WES). Genetic alternations were compared between differently-responded patients. Findings were further validated in multiple public cohorts. Results DNA damage repair (DDR)-related InDel signatures and DDR-related gene mutations were enriched in better-responded patients, i.e., major pathological response (MPR) group. Besides, MPR patients exhibited provoked genome instability and unique homologous recombination deficiency (HRD) events. By further inspecting alternation status of homology-dependent recombination (HR) pathway genes, the clonal alternations were exclusively enriched in MPR group. Additionally, associations between HR gene alternations, percentage of viable tumor cells and HRD event were identified, which orchestrated tumor mutational burden (TMB), mutational intratumor heterogeneity (ITH), somatic copy number alteration (SCNA) ITH and clonal neoantigen load in patients. Validations in public cohorts further supported the generality of our findings. Conclusions We reported for the first time the association between HRD event and enhanced neoadjuvant immunotherapy response in lung cancer. The power of HRD event in patient therapeutic stratification persisted in multifaceted public cohorts. We propose that HR pathway gene status could serve as novel and additional indicators guiding immune-neoadjuvant and immunotherapy treatment decisions for NSCLC patients. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1756-8722 |
| Relation: | https://doaj.org/toc/1756-8722 |
| DOI: | 10.1186/s13045-022-01283-7 |
| URL الوصول: | https://doaj.org/article/e5b3c145d4e041d5a7268eb83cfa42af |
| رقم الأكسشن: | edsdoj.5b3c145d4e041d5a7268eb83cfa42af |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 17568722 |
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| DOI: | 10.1186/s13045-022-01283-7 |