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The correlations of tumor mutational burden among single-region tissue, multi-region tissues and blood in non-small cell lung cancer.
- Source :
-
Journal for immunotherapy of cancer [J Immunother Cancer] 2019 Apr 03; Vol. 7 (1), pp. 98. Date of Electronic Publication: 2019 Apr 03. - Publication Year :
- 2019
-
Abstract
- High-level tissue tumor mutational burden (tTMB) or blood TMB (bTMB) are associated with better response of immunotherapy in non-small cell lung cancer (NSCLC) patients. However, the correlations of single-region tTMB, multi-region tTMB and bTMB remain to be determined. Moreover, whether intratumor heterogeneity (ITH) has impact on TMB should be clarified. We collected multi-region tumor tissues with matched blood from 32 operative NSCLC and evaluated single-region tTMB, multi-region tTMB and bTMB through a 1021-gene panel sequencing. TMB of > 9 mutations/Mb was classified as high. Besides, we used tTMB fold-change to evaluate the influence of the enrolled region number on tTMB. We found both of single-region tTMB and bTMB showed strong correlations with multi-region tTMB, while the former correlated better (Pearson r = 0.94, P = 2E-84; Pearson r = 0.47, P = 0.0067). It showed extremely high specificity (100%) but low sensitivity (43%) when using bTMB to define TMB-high patients, while most false-negative predictions were in early-stage patients. Compared to single region, we found significantly enhanced tTMB fold-change if taking multi-regions for consideration. However, it showed insignificant tTMB fold-change increase if the included regions' number more than three. Moreover, ITH-high patients had significantly higher tTMB fold-change compared with ITH-low patients (2.32 vs. 1.02, P = 8.879e-05). The conversion rate of tTMB level (tTMB-low to tTMB-high) was numerically higher in ITH-high group than that in ITH-low group (16.67% vs. 3.84%). In summary, single-region tTMB has stronger correlation with multi-region tTMB compared with bTMB. ITH has an impact on tTMB, especially in high-level ITH patients.
- Subjects :
- Aged
Antineoplastic Agents, Immunological pharmacology
Antineoplastic Agents, Immunological therapeutic use
Biomarkers, Tumor blood
Biomarkers, Tumor metabolism
Carcinoma, Non-Small-Cell Lung blood
Carcinoma, Non-Small-Cell Lung pathology
Carcinoma, Non-Small-Cell Lung therapy
Costimulatory and Inhibitory T-Cell Receptors antagonists & inhibitors
Costimulatory and Inhibitory T-Cell Receptors immunology
Drug Resistance, Neoplasm genetics
Female
Humans
Lung pathology
Lung surgery
Lung Neoplasms blood
Lung Neoplasms pathology
Lung Neoplasms therapy
Male
Middle Aged
Mutation Rate
Pneumonectomy
Treatment Outcome
Biomarkers, Tumor genetics
Carcinoma, Non-Small-Cell Lung genetics
Genetic Heterogeneity
Lung Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2051-1426
- Volume :
- 7
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal for immunotherapy of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 30944026
- Full Text :
- https://doi.org/10.1186/s40425-019-0581-5