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Concordance Study of a 520-Gene Next-Generation Sequencing-Based Genomic Profiling Assay of Tissue and Plasma Samples

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Abstract

Introduction

Next-generation sequencing (NGS) enables simultaneous detection of actionable somatic variants and estimation of genomic signatures such as tumor mutational burden (TMB) or microsatellite instability (MSI) status, which empowers therapeutic decisions in clinical oncology.

Objective

Our retrospective study investigated the clinical performance of somatic variant detection in paired tissue and blood samples using a large targeted gene panel, the OncoScreen Plus, which interrogates 520 cancer-related genes.

Methods

We analyzed sequencing data derived from paired tissue and blood samples of 3005 patients spanning 20 solid tumor types, including lung (n = 1971), gastrointestinal (n = 625), breast (n = 120) and gynecological (n = 110), genitourinary (n = 38), and other cancers (n = 141).

Results

Across tumor types, the OncoScreen Plus panel achieved a high tissue detection rate, with an average of 97.9%. The average plasma detection rate was 72.2%, with an average tissue concordance rate of 36.6%. Considering all variant types, the plasma assay yielded an average sensitivity/true positive rate of 45.7%, with a positive predictive value of 64.7% relative to tissue assay. Pearson correlation analysis revealed a strong correlation in TMB estimated from blood and tissue samples (correlation coefficient 0.845, R2 = 0.756). MSI-high status was identified in five tumor types, including endometrial cancer (28.6%), colorectal cancer (2.5%), ovarian cancer (2.0%), gastric cancer (1.5%), and lung adenocarcinoma (0.2%).

Conclusion

Paired tumor and blood samples from a large cohort of patients spanning 20 tumor types demonstrated that the OncoScreen Plus is a reliable pan-cancer panel for the accurate detection of somatic variants and genomic signatures that could guide individualized treatment strategies to improve the care of patients with advanced cancer.

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Acknowledgments

The authors thank all the patients and their families for their cooperation and support. We also thank the investigators, study coordinators, operation staff, and the whole project team who worked on this project. We also appreciate the active support of the staff of Burning Rock Biotech, particularly Analyn Lizaso, Jian Wang, Jianxing Xiang, Zhange Chen, Jiaqi Chu, Chanhe Li, Min Li, Yuan Zhou, Jinying Liu, Jing Liu, Wenjie Sun, and Zhou Zhang.

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Author notes

  1. Minghui Wang and Xianshan Chen contributed equally to this work and should be regarded as co-first authors.

Authors and Affiliations

  1. Department of Thoracic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510220, China

    Minghui Wang & Duoguang Wu

  2. Department of Thoracic Surgery, Hainan General Hospital, Hainan, 570311, China

    Xianshan Chen

  3. Department of Oncology, Shengli Clinical Medical College of Fujian Medical University & Fujian Provincial Hospital, Fuzhou, 350001, China

    Yongmei Dai & Li Xie

  4. Department of Pathology, The First People’s Hospital of Foshan, Foshan, 528000, China

    Fang Liu

  5. Department of Pathology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518107, China

    Zheng Yang

  6. Department of Gynecology, Shengli Clinical Medical College of Fujian Medical University & Fujian Provincial Hospital, Fuzhou, 350001, China

    Baozhi Song

  7. Department of Cardiothoracic Surgery, Hwa Mei Hospital, University of Chinese Academy of Sciences (Ningbo No. 2 Hospital), No. 41 Xibei Road, Ningbo, 315010, Zhejiang, China

    Liangwei Yang, Weidi Zhao, Chenxu Zhang & Guofang Zhao

  8. Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang, Harbin, 150081, Heilongjiang, China

    Weixi Shen, Chengjuan Fan, Chong Teng, Xue Zhao, Naisheng Gao, Di Shang & Tao Xin

Authors
  1. Minghui Wang
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  2. Xianshan Chen
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  5. Fang Liu
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  8. Li Xie
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  18. Guofang Zhao
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  19. Tao Xin
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Corresponding authors

Correspondence to Guofang Zhao or Tao Xin.

Ethics declarations

Funding

This study was supported by grants from the National Natural Science Foundation of China (grant number: 81871886 to MW), the Science and Technology Program of Guangzhou, China (grant number: 202103000063 to MW), the Special fund of Foshan Summit Plan General Project (grant number: 2020B004 to FL), the Ningbo Health Branding Subject Fund (grant number: PPXK2018-05 to GZ), The Natural Science Foundation of Ningbo (grant number: 2019A610225 to GZ), the Zhejiang Medicine and Health Science and Technology Project (grant numbers: 2022KY1138 and 2021KY1009 to GZ), The Key Discipline of Hwamei Hospital, University of Chinese Academy of Science (grant number: 2020ZDXK03 to GZ), The Hwamei Fund (grant number: 2019HM to GZ), and the Wu Jieping Medical Foundation (grant number: 320.6750.18105 to TX). The funders had no role in the conceptualization, design, data collection or analysis, decision to publish, or preparation of the manuscript.

Ethical approval and consent to participate

All procedures performed in studies involving human participants were performed in accordance with the Declaration of Helsinki. This study protocol was approved by the ethics committee of The Second Affiliated Hospital of Harbin Medical University (approval number: KY2021-189). Written informed consent was obtained from all participants included in the study.

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Not applicable

Competing interests

Minghui Wang, Xianshan Chen, Yongmei Dai, Duoguang Wu, Fang Liu, Zheng Yang, Baozhi Song, Li Xie, Liangwei Yang, Weidi Zhao, Chenxu Zhang, Weixi Shen, Chengjuan Fan, Chong Teng, Xue Zhao, Naisheng Gao, Di Shang, Guofang Zhao, and Tao Xin have no conflicts of interest that are directly relevant to the content of this article.

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Not applicable.

Availability of data and material

All authors confirm adherence to the policy. The data that support the findings of this study are available from the corresponding author upon reasonable request.

Code availability

Not applicable.

Author contributions

MW, YD, GZ, and TX conceived of the study and drafted the manuscript. MW, FL, GZ, and TX acquired funding. All the authors collected and analyzed the clinical data, participated in the data interpretation, data analysis, and manuscript writing and editing. XC contributed significantly to the data analysis and interpretation during the manuscript revision. All authors contributed to the revision and approved the final manuscript.

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Wang, M., Chen, X., Dai, Y. et al. Concordance Study of a 520-Gene Next-Generation Sequencing-Based Genomic Profiling Assay of Tissue and Plasma Samples. Mol Diagn Ther 26, 309–322 (2022). https://doi.org/10.1007/s40291-022-00579-1

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  • DOI: https://doi.org/10.1007/s40291-022-00579-1

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