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

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...

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Autores principales: Qiu, Yuan, Liu, Liping, Yang, Haihong, Chen, Hanzhang, Deng, Qiuhua, Xiao, Dakai, Lin, Yongping, Zhu, Changbin, Li, Weiwei, Shao, Di, Jiang, Wenxi, Wu, Kui, He, Jianxing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121003/
https://www.ncbi.nlm.nih.gov/pubmed/33996530
http://dx.doi.org/10.3389/fonc.2020.608989
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author Qiu, Yuan
Liu, Liping
Yang, Haihong
Chen, Hanzhang
Deng, Qiuhua
Xiao, Dakai
Lin, Yongping
Zhu, Changbin
Li, Weiwei
Shao, Di
Jiang, Wenxi
Wu, Kui
He, Jianxing
author_facet Qiu, Yuan
Liu, Liping
Yang, Haihong
Chen, Hanzhang
Deng, Qiuhua
Xiao, Dakai
Lin, Yongping
Zhu, Changbin
Li, Weiwei
Shao, Di
Jiang, Wenxi
Wu, Kui
He, Jianxing
author_sort Qiu, Yuan
collection PubMed
description 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.
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spelling pubmed-81210032021-05-15 Integrating Histologic and Genomic Characteristics to Predict Tumor Mutation Burden of Early-Stage Non-Small-Cell Lung Cancer Qiu, Yuan Liu, Liping Yang, Haihong Chen, Hanzhang Deng, Qiuhua Xiao, Dakai Lin, Yongping Zhu, Changbin Li, Weiwei Shao, Di Jiang, Wenxi Wu, Kui He, Jianxing Front Oncol Oncology 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. Frontiers Media S.A. 2021-04-30 /pmc/articles/PMC8121003/ /pubmed/33996530 http://dx.doi.org/10.3389/fonc.2020.608989 Text en Copyright © 2021 Qiu, Liu, Yang, Chen, Deng, Xiao, Lin, Zhu, Li, Shao, Jiang, Wu and He https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Qiu, Yuan
Liu, Liping
Yang, Haihong
Chen, Hanzhang
Deng, Qiuhua
Xiao, Dakai
Lin, Yongping
Zhu, Changbin
Li, Weiwei
Shao, Di
Jiang, Wenxi
Wu, Kui
He, Jianxing
Integrating Histologic and Genomic Characteristics to Predict Tumor Mutation Burden of Early-Stage Non-Small-Cell Lung Cancer
title Integrating Histologic and Genomic Characteristics to Predict Tumor Mutation Burden of Early-Stage Non-Small-Cell Lung Cancer
title_full Integrating Histologic and Genomic Characteristics to Predict Tumor Mutation Burden of Early-Stage Non-Small-Cell Lung Cancer
title_fullStr Integrating Histologic and Genomic Characteristics to Predict Tumor Mutation Burden of Early-Stage Non-Small-Cell Lung Cancer
title_full_unstemmed Integrating Histologic and Genomic Characteristics to Predict Tumor Mutation Burden of Early-Stage Non-Small-Cell Lung Cancer
title_short Integrating Histologic and Genomic Characteristics to Predict Tumor Mutation Burden of Early-Stage Non-Small-Cell Lung Cancer
title_sort integrating histologic and genomic characteristics to predict tumor mutation burden of early-stage non-small-cell lung cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121003/
https://www.ncbi.nlm.nih.gov/pubmed/33996530
http://dx.doi.org/10.3389/fonc.2020.608989
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