Integrating Histologic and Genomic Characteristics to Predict Tumor Mutation Burden of Early-Stage Non-Small-Cell Lung Cancer

被引:13
|
作者
Qiu, Yuan [1 ,2 ]
Liu, Liping [1 ,2 ,3 ]
Yang, Haihong [1 ,2 ]
Chen, Hanzhang [1 ,2 ]
Deng, Qiuhua [1 ,2 ]
Xiao, Dakai [1 ,2 ]
Lin, Yongping [1 ,2 ]
Zhu, Changbin [4 ]
Li, Weiwei [4 ]
Shao, Di [4 ]
Jiang, Wenxi [4 ]
Wu, Kui [4 ,5 ,6 ]
He, Jianxing [1 ,2 ]
机构
[1] Guangzhou Med Univ, Natl Clin Res Ctr Resp Dis, Affiliated Hosp 1, Guangzhou, Peoples R China
[2] Guangzhou Med Univ, State Key Lab Resp Dis, Affiliated Hosp 1, Guangzhou, Peoples R China
[3] Guangzhou Med Univ, Translat Med Lab, Affiliated Hosp 1, Guangzhou, Peoples R China
[4] BGI Shenzhen, BGI Genom, Shenzhen, Peoples R China
[5] BGI Shenzhen, Shenzhen, Peoples R China
[6] China Natl GeneBank BGI Shenzhen, Shenzhen, Peoples R China
来源
FRONTIERS IN ONCOLOGY | 2021年 / 10卷
基金
中国国家自然科学基金;
关键词
early-stage non-small-cell lung cancer; tumor mutation burden (TMB); histology; genomics; model; MICROPAPILLARY; NODE; EGFR;
D O I
10.3389/fonc.2020.608989
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Tumor mutation burden (TMB) serves as an effective biomarker predicting efficacy of mono-immunotherapy for non-small cell lung cancer (NSCLC). Establishing a precise TMB predicting model is essential to select which populations are likely to respond to immunotherapy or prognosis and to maximize the benefits of treatment. In this study, available Formalin-fixed paraffin embedded tumor tissues were collected from 499 patients with NSCLC. Targeted sequencing of 636 cancer related genes was performed, and TMB was calculated. Distribution of TMB was significantly (p < 0.001) correlated with sex, clinical features (pathological/histological subtype, pathological stage, lymph node metastasis, and lympho-vascular invasion). It was also significantly (p < 0.001) associated with mutations in genes like TP53, EGFR, PIK3CA, KRAS, EPHA3, TSHZ3, FAT3, NAV3, KEAP1, NFE2L2, PTPRD, LRRK2, STK11, NF1, KMT2D, and GRIN2A. No significant correlations were found between TMB and age, neuro-invasion (p = 0.125), and tumor location (p = 0.696). Patients with KRAS p.G12 mutations and FAT3 missense mutations were associated (p < 0.001) with TMB. TP53 mutations also influence TMB distribution (P < 0.001). TMB was reversely related to EGFR mutations (P < 0.001) but did not differ by mutation types. According to multivariate logistic regression model, genomic parameters could effectively construct model predicting TMB, which may be improved by introducing clinical information. Our study demonstrates that genomic together with clinical features yielded a better reliable model predicting TMB-high status. A simplified model consisting of less than 20 genes and couples of clinical parameters were sought to be useful to provide TMB status with less cost and waiting time.
引用
收藏
页数:10
相关论文
共 50 条
  • [1] Integrating histologic and genomic characteristics to predict tumour mutation burden of early-stage non-small cell lung cancer
    Qiu, Y.
    Shao, D.
    Liu, L.
    Lin, Y.
    Wu, K.
    He, J.
    [J]. ANNALS OF ONCOLOGY, 2020, 31 : S1401 - S1401
  • [2] Integrating Imaging, Histologic, and Genetic Features to Predict Tumor Mutation Burden of Non-Small-Cell Lung Cancer
    Zhang, Nasha
    Wu, Jia
    Yu, Jinming
    Zhu, Hui
    Yang, Ming
    Li, Ruijiang
    [J]. CLINICAL LUNG CANCER, 2020, 21 (03) : E151 - E163
  • [3] Circulating tumor DNA detection is correlated to histologic types in patients with early-stage non-small-cell lung cancer
    Zhang, Bin
    Niu, Xueliang
    Zhang, Qiang
    Wang, Chunli
    Liu, Bo
    Yue, Dongsheng
    Li, Chenguang
    Giaccone, Giuseppe
    Li, Shiyong
    Gao, Liuwei
    Zhang, Hua
    Wang, Jian
    Yang, Huanming
    Wu, Renhua
    Ni, Peixiang
    Wang, Changli
    Ye, Mingzhi
    Liu, Weiran
    [J]. LUNG CANCER, 2019, 134 : 108 - 116
  • [4] Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer
    Wakelee, Heather
    Liberman, Moishe
    Kato, Terufumi
    Tsuboi, Masahiro
    Lee, Se-Hoon
    Gao, Shugeng
    Chen, Ke-Neng
    Dooms, Christophe
    Majem, Margarita
    Eigendorff, Ekkehard
    Martinengo, Gaston L.
    Bylicki, Olivier
    Rodriguez-Abreu, Delvys
    Chaft, Jamie E. E.
    Novello, Silvia
    Yang, Jing
    Keller, Steven M. M.
    Samkari, Ayman
    Spicer, Jonathan D. D.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2023, 389 (06): : 491 - 503
  • [5] SURVIVAL IN EARLY-STAGE NON-SMALL-CELL LUNG-CANCER
    NESBITT, JC
    PUTNAM, JB
    WALSH, GL
    ROTH, JA
    MOUNTAIN, CF
    [J]. ANNALS OF THORACIC SURGERY, 1995, 60 (02): : 466 - 472
  • [6] Management of early-stage non-small-cell lung cancer (NSCLC)
    Le Chevalier, Thierry
    [J]. EUROPEAN JOURNAL OF CANCER, 2011, 47 : S292 - S293
  • [7] Accelerated hypofractionation for early-stage non-small-cell lung cancer
    Cheung, PCF
    Yeung, LTF
    Basrur, V
    Ung, YC
    Balogh, J
    Danjoux, CE
    [J]. INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2002, 54 (04): : 1014 - 1023
  • [8] Tumor Mutation Burden as a Biomarker in Resected Non-Small-Cell Lung Cancer
    Devarakonda, Siddhartha
    Rotolo, Federico
    Tsao, Ming-Sound
    Lanc, Irena
    Brambilla, Elisabeth
    Masood, Ashiq
    Olaussen, Ken A.
    Fulton, Robert
    Sakashita, Shingo
    McLeer-Florin, Anne
    Ding, Keyue
    Le Teuff, Gwenael
    Shepherd, Frances A.
    Pignon, Jean-Pierre
    Graziano, Stephen L.
    Kratzke, Robert
    Soria, Jean-Charles
    Seymour, Lesley
    Govindan, Ramaswamy
    Michiels, Stefan
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2018, 36 (30) : 2995 - +
  • [9] VEGF polymorphisms and survival in early-stage non-small-cell lung cancer
    Heist, Rebecca Suk
    Zhai, Rihong
    Liu, Geoffrey
    Zhou, Wei
    Lin, Xihong
    Su, Li
    Asomaning, Kofi
    Lynch, Thomas J.
    Wain, John C.
    Christiani, David C.
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (06) : 856 - 862
  • [10] ACR Appropriateness Criteria® Early-Stage Non-Small-Cell Lung Cancer
    Videtic, Gregory M. M.
    Chang, Joe Yujiao
    Chetty, Indrin J.
    Ginsburg, Mark E.
    Kestin, Larry L.
    Kong, Feng-Ming
    Lally, Brian E.
    Loo, Billy W., Jr.
    Movsas, Benjamin
    Stinchcombe, Thomas E.
    Willers, Henning
    Rosenzweig, Kenneth E.
    [J]. AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS, 2014, 37 (02): : 201 - 207