The correlations of tumor mutational burden among single-region tissue, multi-region tissues and blood in non-small cell lung cancer

Li Zhang, Yaxiong Zhang, Lianpeng Chang, Yunpeng Yang, Wenfeng Fang, Yanfang Guan, Aiwei Wu, Shaodong Hong, Huaqiang Zhou, Gang Chen, Xi Chen, Shen Zhao, Qiufan Zheng, Hui Pan, Lanjun Zhang, Hao Long, Haoxian Yang, Xin Wang, Zhesheng Wen, Junye WangHong Yang, Xuefeng Xia, Yuanyuan Zhao, Xue Hou, Yuxiang Ma, Ting Zhou, Zhonghan Zhang, Jianhua Zhan, Yan Huang, Hongyun Zhao, Ningning Zhou, Xin Yi

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Article number98
JournalJournal for immunotherapy of cancer
Volume7
Issue number1
DOIs
StatePublished - Apr 3 2019

Fingerprint

Tumor Burden
Non-Small Cell Lung Carcinoma

Keywords

  • Blood TMB
  • ITH
  • NSCLC
  • Tissue TMB
  • bTMB
  • tTMB

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Cite this

The correlations of tumor mutational burden among single-region tissue, multi-region tissues and blood in non-small cell lung cancer. / Zhang, Li; Zhang, Yaxiong; Chang, Lianpeng; Yang, Yunpeng; Fang, Wenfeng; Guan, Yanfang; Wu, Aiwei; Hong, Shaodong; Zhou, Huaqiang; Chen, Gang; Chen, Xi; Zhao, Shen; Zheng, Qiufan; Pan, Hui; Zhang, Lanjun; Long, Hao; Yang, Haoxian; Wang, Xin; Wen, Zhesheng; Wang, Junye; Yang, Hong; Xia, Xuefeng; Zhao, Yuanyuan; Hou, Xue; Ma, Yuxiang; Zhou, Ting; Zhang, Zhonghan; Zhan, Jianhua; Huang, Yan; Zhao, Hongyun; Zhou, Ningning; Yi, Xin.

In: Journal for immunotherapy of cancer, Vol. 7, No. 1, 98, 03.04.2019.

Research output: Contribution to journalArticle

Zhang, L, Zhang, Y, Chang, L, Yang, Y, Fang, W, Guan, Y, Wu, A, Hong, S, Zhou, H, Chen, G, Chen, X, Zhao, S, Zheng, Q, Pan, H, Zhang, L, Long, H, Yang, H, Wang, X, Wen, Z, Wang, J, Yang, H, Xia, X, Zhao, Y, Hou, X, Ma, Y, Zhou, T, Zhang, Z, Zhan, J, Huang, Y, Zhao, H, Zhou, N & Yi, X 2019, 'The correlations of tumor mutational burden among single-region tissue, multi-region tissues and blood in non-small cell lung cancer', Journal for immunotherapy of cancer, vol. 7, no. 1, 98. https://doi.org/10.1186/s40425-019-0581-5
Zhang, Li ; Zhang, Yaxiong ; Chang, Lianpeng ; Yang, Yunpeng ; Fang, Wenfeng ; Guan, Yanfang ; Wu, Aiwei ; Hong, Shaodong ; Zhou, Huaqiang ; Chen, Gang ; Chen, Xi ; Zhao, Shen ; Zheng, Qiufan ; Pan, Hui ; Zhang, Lanjun ; Long, Hao ; Yang, Haoxian ; Wang, Xin ; Wen, Zhesheng ; Wang, Junye ; Yang, Hong ; Xia, Xuefeng ; Zhao, Yuanyuan ; Hou, Xue ; Ma, Yuxiang ; Zhou, Ting ; Zhang, Zhonghan ; Zhan, Jianhua ; Huang, Yan ; Zhao, Hongyun ; Zhou, Ningning ; Yi, Xin. / The correlations of tumor mutational burden among single-region tissue, multi-region tissues and blood in non-small cell lung cancer. In: Journal for immunotherapy of cancer. 2019 ; Vol. 7, No. 1.
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AU - Zhang, Li

AU - Zhang, Yaxiong

AU - Chang, Lianpeng

AU - Yang, Yunpeng

AU - Fang, Wenfeng

AU - Guan, Yanfang

AU - Wu, Aiwei

AU - Hong, Shaodong

AU - Zhou, Huaqiang

AU - Chen, Gang

AU - Chen, Xi

AU - Zhao, Shen

AU - Zheng, Qiufan

AU - Pan, Hui

AU - Zhang, Lanjun

AU - Long, Hao

AU - Yang, Haoxian

AU - Wang, Xin

AU - Wen, Zhesheng

AU - Wang, Junye

AU - Yang, Hong

AU - Xia, Xuefeng

AU - Zhao, Yuanyuan

AU - Hou, Xue

AU - Ma, Yuxiang

AU - Zhou, Ting

AU - Zhang, Zhonghan

AU - Zhan, Jianhua

AU - Huang, Yan

AU - Zhao, Hongyun

AU - Zhou, Ningning

AU - Yi, Xin

PY - 2019/4/3

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N2 - 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.

AB - 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.

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