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Prediction of tumor mutation burden in breast cancer based on the expression of ER, PR, HER-2, and Ki-67

OBJECTIVE: Cancer immunoediting is the process of eliminating highly immunogenic tumor cells by somatic evolution and protecting the host from tumor development in the host immune system. Frequencies of somatic mutations or tumor mutation burden (TMB) were associated with immunogenicity of breast ca...

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Autores principales: Xu, Junnan, Guo, Xiangyu, Jing, Mingxi, Sun, Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5914885/
https://www.ncbi.nlm.nih.gov/pubmed/29719409
http://dx.doi.org/10.2147/OTT.S159830
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author Xu, Junnan
Guo, Xiangyu
Jing, Mingxi
Sun, Tao
author_facet Xu, Junnan
Guo, Xiangyu
Jing, Mingxi
Sun, Tao
author_sort Xu, Junnan
collection PubMed
description OBJECTIVE: Cancer immunoediting is the process of eliminating highly immunogenic tumor cells by somatic evolution and protecting the host from tumor development in the host immune system. Frequencies of somatic mutations or tumor mutation burden (TMB) were associated with immunogenicity of breast cancer. This study aimed to predict the level of TMB in patients with breast cancer by the expression of estrogen (ER), progesterone (PR), HER-2, and Ki-67, thereby anticipating the prognosis of patients and the possible response to immunotherapy. PATIENTS AND METHODS: In 53 patients with breast cancer, the 453 multigenes panel based on NGS was used to determine the TMB value of breast cancer in the patient’s primary tumor tissues. The predicted TMB value was divided into 4 groups: A (0–3.33), B (3.33–5.56), C (5.56–8.89), and D (>8.89), according to the quartile method, with group A as reference level. Logistic regression was used to analyze the risk ratio of each molecule type, and the prediction model was established. Survival probabilities by covariates were assessed using Kaplan–Meier estimator survival analysis and Cox’s proportional hazards models. RESULTS: In 53 patients, the TMB value measured by the NGS polygenic panel was between 0 and 14.4/Mb. TMB distribution in 53 cases of breast cancer tissue: 18 cases in A group, 22 cases in B group, 10 cases in C group, and 3 cases in D group. HER-2 expression positivity was significantly associated with TMB (HER-2 positive vs HER-2 negative, odds ratio [OR] =34.81, 95% confidence interval [CI]: 3.711–821.689, P=0.0065). Higher TMB was distributed in the patients who were Ki-67 expression positive (>14%) than those who were Ki-67 expression negative (≤14%) (OR =0.217, 95% CI: 0.054–0.806, P=0.0242). However, no significant differences of TMB were found between ER-positive group and ER-negative group (OR =3.133, 95% CI: 0.124–127.687, P=0.4954) and between PR-positive group and PR-negative group in terms of TMB (OR =1.702, 95% CI: 0.162–20.335, P=0.6492). The predicted model is TMB = −1.14×ER +0.53×PR +3.55×HER-2-1.53×Ki-67+ CONSTANT (INTERCEPT). Patients with low TMB had a better disease-free survival (DFS) than those with high TMB (83 vs 59 m, P=0.002). In a multivariate analysis, high TMB (>5.56) was an independent predictive factor for decreased DFS (adjusted hazard ratio [HR], 5.594; 95% CI: 1.694–18.473; P = 0.005). CONCLUSION: The preliminary results suggest that the level of TMB value in patients with breast cancer can be predicted based on the expression levels of ER, PR, HER-2, and Ki-67, which may indicate the prognostic and predictive value of immunotherapy in patients with breast cancer.
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spelling pubmed-59148852018-05-01 Prediction of tumor mutation burden in breast cancer based on the expression of ER, PR, HER-2, and Ki-67 Xu, Junnan Guo, Xiangyu Jing, Mingxi Sun, Tao Onco Targets Ther Original Research OBJECTIVE: Cancer immunoediting is the process of eliminating highly immunogenic tumor cells by somatic evolution and protecting the host from tumor development in the host immune system. Frequencies of somatic mutations or tumor mutation burden (TMB) were associated with immunogenicity of breast cancer. This study aimed to predict the level of TMB in patients with breast cancer by the expression of estrogen (ER), progesterone (PR), HER-2, and Ki-67, thereby anticipating the prognosis of patients and the possible response to immunotherapy. PATIENTS AND METHODS: In 53 patients with breast cancer, the 453 multigenes panel based on NGS was used to determine the TMB value of breast cancer in the patient’s primary tumor tissues. The predicted TMB value was divided into 4 groups: A (0–3.33), B (3.33–5.56), C (5.56–8.89), and D (>8.89), according to the quartile method, with group A as reference level. Logistic regression was used to analyze the risk ratio of each molecule type, and the prediction model was established. Survival probabilities by covariates were assessed using Kaplan–Meier estimator survival analysis and Cox’s proportional hazards models. RESULTS: In 53 patients, the TMB value measured by the NGS polygenic panel was between 0 and 14.4/Mb. TMB distribution in 53 cases of breast cancer tissue: 18 cases in A group, 22 cases in B group, 10 cases in C group, and 3 cases in D group. HER-2 expression positivity was significantly associated with TMB (HER-2 positive vs HER-2 negative, odds ratio [OR] =34.81, 95% confidence interval [CI]: 3.711–821.689, P=0.0065). Higher TMB was distributed in the patients who were Ki-67 expression positive (>14%) than those who were Ki-67 expression negative (≤14%) (OR =0.217, 95% CI: 0.054–0.806, P=0.0242). However, no significant differences of TMB were found between ER-positive group and ER-negative group (OR =3.133, 95% CI: 0.124–127.687, P=0.4954) and between PR-positive group and PR-negative group in terms of TMB (OR =1.702, 95% CI: 0.162–20.335, P=0.6492). The predicted model is TMB = −1.14×ER +0.53×PR +3.55×HER-2-1.53×Ki-67+ CONSTANT (INTERCEPT). Patients with low TMB had a better disease-free survival (DFS) than those with high TMB (83 vs 59 m, P=0.002). In a multivariate analysis, high TMB (>5.56) was an independent predictive factor for decreased DFS (adjusted hazard ratio [HR], 5.594; 95% CI: 1.694–18.473; P = 0.005). CONCLUSION: The preliminary results suggest that the level of TMB value in patients with breast cancer can be predicted based on the expression levels of ER, PR, HER-2, and Ki-67, which may indicate the prognostic and predictive value of immunotherapy in patients with breast cancer. Dove Medical Press 2018-04-19 /pmc/articles/PMC5914885/ /pubmed/29719409 http://dx.doi.org/10.2147/OTT.S159830 Text en © 2018 Xu et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Xu, Junnan
Guo, Xiangyu
Jing, Mingxi
Sun, Tao
Prediction of tumor mutation burden in breast cancer based on the expression of ER, PR, HER-2, and Ki-67
title Prediction of tumor mutation burden in breast cancer based on the expression of ER, PR, HER-2, and Ki-67
title_full Prediction of tumor mutation burden in breast cancer based on the expression of ER, PR, HER-2, and Ki-67
title_fullStr Prediction of tumor mutation burden in breast cancer based on the expression of ER, PR, HER-2, and Ki-67
title_full_unstemmed Prediction of tumor mutation burden in breast cancer based on the expression of ER, PR, HER-2, and Ki-67
title_short Prediction of tumor mutation burden in breast cancer based on the expression of ER, PR, HER-2, and Ki-67
title_sort prediction of tumor mutation burden in breast cancer based on the expression of er, pr, her-2, and ki-67
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5914885/
https://www.ncbi.nlm.nih.gov/pubmed/29719409
http://dx.doi.org/10.2147/OTT.S159830
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