NDLI: A novel tumor mutational burden estimation model as a predictive and prognostic biomarker in NSCLC patients

Content Provider	Springer Nature : BioMed Central
Author	Tian, Yanhua Xu, Jiachen Chu, Qian Duan, Jianchun Zhang, Jianjun Bai, Hua Yang, Zhenlin Fang, Wenfeng Cai, Liangliang Wan, Rui Fei, Kailun He, Jie Gao, Shugeng Zhang, Li Wang, Zhijie Wang, Jie
Abstract	Background Tumor mutational burden (TMB) has both prognostic value in resected non-small cell lung cancer (NSCLC) patients and predictive value for immunotherapy response. However, TMB evaluation by whole-exome sequencing (WES) is expensive and time-consuming, hampering its application in clinical practice. In our study, we aimed to construct a mutational burden estimation model, with a small set of genes, that could precisely estimate WES-TMB and, at the same time, has prognostic and predictive value for NSCLC patients. Methods TMB estimation model was trained based on genomic data from 1056 NSCLC samples from The Cancer Genome Atlas (TCGA). Validation was performed using three independent cohorts, including Rizvi cohort and our own Asian cohorts, including 89 early-stage and n late-stage Asian NSCLC patients, respectively. TCGA data were obtained on September 3, 2018. The two Asian cohort studies were performed from September 1, 2018, to March 5, 2019. Pearson’s correlation coefficient was used to assess the performance of estimated TMB with WES-TMB. The Kaplan-Meier survival analysis was applied to evaluate the association of estimated TMB with disease-free survival (DFS), overall survival (OS), and response to anti-programmed death-1 (PD-1) and anti-programmed death-ligand 1 (PD-L1) therapy. Results The estimation model, consisted of only 23 genes, correlated well with WES-TMB both in the training set of TCGA cohort and validation set of Rizvi cohort and our own Asian cohort. Estimated TMB by the 23-gene panel was significantly associated with DFS and OS in patients with early-stage NSCLC and could serve as a predictive biomarker for anti-PD-1 and anti-PD-L1 treatment response. Conclusions The 23-gene panel, instead of WES or the currently used panel-based methods, could be used to assess the WES-TMB with a high relevance. This customized targeted sequencing panel could be easily applied into clinical practice to predict the immunotherapy response and prognosis of NSCLC.
Related Links	https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01694-8.pdf
Ending Page	11
Page Count	11
Starting Page	1
File Format	HTM / HTML
ISSN	17417015
DOI	10.1186/s12916-020-01694-8
Journal	BMC Medicine
Issue Number	1
Volume Number	18
Language	English
Publisher	BioMed Central
Publisher Date	2020-08-26
Access Restriction	Open
Subject Keyword	Medicine Public Health Biomedicine TMB estimation 23-gene panel Prognostic and predictive value Non-small cell lung cancer Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Medicine
Journal Impact Factor	7.1/2023
5-Year Journal Impact Factor	8.8/2023

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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