Lung cancer-associated T cell repertoire as potential biomarker for early detection of stage I lung cancer

Min Li; Chunliu Zhang; Shichao Deng; Li Li; Shiqing Liu; Jing Bai; Yaping Xu; Yanfang Guan; Xuefeng Xia; Lunquan Sun; David P Carbone; Chengping Hu

doi:10.1016/j.lungcan.2021.09.017

Lung cancer-associated T cell repertoire as potential biomarker for early detection of stage I lung cancer

Lung Cancer. 2021 Dec:162:16-22. doi: 10.1016/j.lungcan.2021.09.017. Epub 2021 Sep 28.

Authors

Min Li¹, Chunliu Zhang², Shichao Deng³, Li Li³, Shiqing Liu⁴, Jing Bai², Yaping Xu², Yanfang Guan², Xuefeng Xia², Lunquan Sun⁵, David P Carbone⁶, Chengping Hu⁷

Affiliations

¹ Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, China; Xiangya Lung Cancer Center, Xiangya Hospital, Central South University, Changsha, China; Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, China; Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, China; James Cancer Center, The Ohio State University Medical Center, Columbus, USA.
² Geneplus-Beijing Institute, Beijing, China.
³ Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, China.
⁴ Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, China; Xiangya Lung Cancer Center, Xiangya Hospital, Central South University, Changsha, China; Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, China.
⁵ Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Changsha, China.
⁶ James Cancer Center, The Ohio State University Medical Center, Columbus, USA.
⁷ Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, China; Xiangya Lung Cancer Center, Xiangya Hospital, Central South University, Changsha, China; Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Changsha, China. Electronic address: huchengp28@126.com.

PMID: 34649105
DOI: 10.1016/j.lungcan.2021.09.017

Abstract

Background: Early detection of lung cancer in asymptomatic patients remains challenging, especially for stage I. Considering the substantial interaction with tumor immunogenicity, we hypothesized that lung cancer-associated TCR (LC-aTCR) may serve as potential biomarker in early detection of stage I lung cancer.

Methods: Individuals who received low-dose computed tomography (LDCT) screening were enrolled in the study. Surgical tissues and peripheral blood specimens were collected and performed with DNA-based T cell repertoire (TCR) sequencing. The motif-based algorithm was used to deconstruct specific lung cancer-associated TCRs (LC-aTCRs).

Results: A total of 146 individuals participating in the real-world LDCT screening project were enrolled in this study, including 52 patients with pathologically-confirmed stage I lung cancer and 94 non-cancer controls. We developed a motif-based algorithm to define 80 LC-aTCRs in the training cohort. Moreover, in the validation cohort, high sensitivity and specificity was showed in stage I lung cancer with 72% and 91% respectively, and the AUC of the ROC curve was 0.91 (95% CI: 0.85 ∼ 0.96).

Conclusion: This work provides inspiration for stage I lung cancer detection by using blood TCR profiling data. The combination of TCR-based assay and routine screening deserves further testing in larger cohorts.

Keywords: Biomarker; Early detection; Lung cancer; Lung cancer-associated TCRs; Stage I.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Early Detection of Cancer
Humans
Lung Neoplasms* / diagnosis
T-Lymphocytes
Tomography, X-Ray Computed

Substances

Biomarkers