A novel tumor mutational burden estimation model as a predictive and prognostic biomarker in NSCLC patients.
BMC Med
; 18(1): 232, 2020 08 26.
Article
en En
| MEDLINE
| ID: mdl-32843031
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.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Biomarcadores de Tumor
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Carcinoma de Pulmón de Células no Pequeñas
/
Inmunoterapia
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Neoplasias Pulmonares
Tipo de estudio:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
BMC Med
Asunto de la revista:
MEDICINA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China