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Homologous recombination deficiency (HRD) can predict the therapeutic outcomes of immuno-neoadjuvant therapy in NSCLC patients.
Zhou, Zhen; Ding, Zhengping; Yuan, Jie; Shen, Shengping; Jian, Hong; Tan, Qiang; Yang, Yunhai; Chen, Zhiwei; Luo, Qingquan; Cheng, Xinghua; Yu, Yongfeng; Niu, Xiaomin; Qian, Liqiang; Chen, Xiaoke; Gu, Linping; Liu, Ruijun; Ma, Shenglin; Huang, Jia; Chen, Tianxiang; Li, Ziming; Ji, Wenxiang; Song, Liwei; Shen, Lan; Jiang, Long; Yu, Zicheng; Zhang, Chao; Tai, Zaixian; Wang, Changxi; Chen, Rongrong; Carbone, David P; Xia, Xuefeng; Lu, Shun.
Afiliação
  • Zhou Z; Department of Medical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Ding Z; Department of Surgical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Yuan J; Geneplus-Shenzhen, Shenzhen, China.
  • Shen S; Department of Medical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Jian H; Department of Medical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Tan Q; Department of Surgical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Yang Y; Department of Surgical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Chen Z; Department of Medical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Luo Q; Department of Surgical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Cheng X; Department of Surgical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Yu Y; Department of Medical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Niu X; Department of Medical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Qian L; Department of Surgical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Chen X; Department of Surgical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Gu L; Department of Medical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Liu R; Department of Surgical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Ma S; Department of Oncology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Huang J; Department of Surgical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Chen T; Department of Surgical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Li Z; Department of Medical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Ji W; Department of Medical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Song L; Department of Surgical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Shen L; Department of Medical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Jiang L; Department of Surgical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Yu Z; Geneplus-Shenzhen, Shenzhen, China.
  • Zhang C; Geneplus-Shenzhen, Shenzhen, China.
  • Tai Z; Geneplus-Shenzhen, Shenzhen, China.
  • Wang C; Geneplus-Shenzhen, Shenzhen, China.
  • Chen R; Geneplus-Beijing, Beijing, China.
  • Carbone DP; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
  • Xia X; Geneplus-Beijing, Beijing, China.
  • Lu S; Department of Medical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. shunlu@sjtu.edu.cn.
J Hematol Oncol ; 15(1): 62, 2022 05 18.
Article em En | MEDLINE | ID: mdl-35585646
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Pulmonar de Células não Pequenas / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: J Hematol Oncol Assunto da revista: HEMATOLOGIA / NEOPLASIAS Ano de publicação: 2022 Tipo de documento: Article País de afiliação: China
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Pulmonar de Células não Pequenas / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: J Hematol Oncol Assunto da revista: HEMATOLOGIA / NEOPLASIAS Ano de publicação: 2022 Tipo de documento: Article País de afiliação: China