The Deep Learning Framework iCanTCR Enables Early Cancer Detection Using the T-cell Receptor Repertoire in Peripheral Blood.

Journal: Cancer research
PMID:

Abstract

UNLABELLED: T cells recognize tumor antigens and initiate an anticancer immune response in the very early stages of tumor development, and the antigen specificity of T cells is determined by the T-cell receptor (TCR). Therefore, monitoring changes in the TCR repertoire in peripheral blood may offer a strategy to detect various cancers at a relatively early stage. Here, we developed the deep learning framework iCanTCR to identify patients with cancer based on the TCR repertoire. The iCanTCR framework uses TCRβ sequences from an individual as an input and outputs the predicted cancer probability. The model was trained on over 2,000 publicly available TCR repertoires from 11 types of cancer and healthy controls. Analysis of several additional publicly available datasets validated the ability of iCanTCR to distinguish patients with cancer from noncancer individuals and demonstrated the capability of iCanTCR for the accurate classification of multiple cancers. Importantly, iCanTCR precisely identified individuals with early-stage cancer with an AUC of 86%. Altogether, this work provides a liquid biopsy approach to capture immune signals from peripheral blood for noninvasive cancer diagnosis.

Authors

  • Yideng Cai
    School of Computer Science and Engineering, Central South University, Changsha 410083, China.
  • Meng Luo
    Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, China; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China.
  • Wenyi Yang
    School of Software, Central South University, Changsha, 410075, China.
  • Chang Xu
    Institute of Cardio-Cerebrovascular Medicine, Central Hospital of Dalian University of Technology, Dalian 116089, China.
  • Pingping Wang
    School of Electrical and Information Engineering, Tianjin University, 300072, Tianjin, China.
  • Guangfu Xue
    School of Life Science and Technology, Harbin Institute of Technology, Harbin 150006, China.
  • Xiyun Jin
    Center for Bioinformatics, School of Life Science and Technology, Harbin Institute of Technology, Harbin, 150000, China.
  • Rui Cheng
    Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China.
  • Jinhao Que
    School of Life Science and Technology, Harbin Institute of Technology, Harbin 150006, China.
  • Wenyang Zhou
    School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China.
  • Boran Pang
    Center for Difficult and Complicated Abdominal Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
  • Shouping Xu
    Department of Radiotherapy, First Medical Center of PLA General Hospital, BeiJing 100853, P.R.China.
  • Yu Li
    Department of Public Health, Shihezi University School of Medicine, 832000, China.
  • Qinghua Jiang
    School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
  • Zhaochun Xu
    Computer Department, Jingdezhen Ceramic University, Jingdezhen, China.