Development and validation of the immune signature to predict distant metastasis in patients with nasopharyngeal carcinoma
BackgroundThe tumor immune microenvironment has clinicopathological significance in predicting prognosis and therapeutic efficacy. We aimed to develop an immune signature to predict distant metastasis in patients with nasopharyngeal carcinoma (NPC).MethodsUsing multiplexed quantitative fluorescence,...
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BMJ Publishing Group
2020-06-01
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Series: | Journal for ImmunoTherapy of Cancer |
Online Access: | https://jitc.bmj.com/content/8/1/e000205.full |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sai-Lan Liu Li-Juan Bian Qiu-Yan Chen Xue-Song Sun Dong-Hua Luo Xiao-Yun Li Bei-Bei Xiao Jin-Jie Yan Zi-Jian Lu Lin-Quan Tang Hai-Qiang Mai |
spellingShingle |
Sai-Lan Liu Li-Juan Bian Qiu-Yan Chen Xue-Song Sun Dong-Hua Luo Xiao-Yun Li Bei-Bei Xiao Jin-Jie Yan Zi-Jian Lu Lin-Quan Tang Hai-Qiang Mai Development and validation of the immune signature to predict distant metastasis in patients with nasopharyngeal carcinoma Journal for ImmunoTherapy of Cancer |
author_facet |
Sai-Lan Liu Li-Juan Bian Qiu-Yan Chen Xue-Song Sun Dong-Hua Luo Xiao-Yun Li Bei-Bei Xiao Jin-Jie Yan Zi-Jian Lu Lin-Quan Tang Hai-Qiang Mai |
author_sort |
Sai-Lan Liu |
title |
Development and validation of the immune signature to predict distant metastasis in patients with nasopharyngeal carcinoma |
title_short |
Development and validation of the immune signature to predict distant metastasis in patients with nasopharyngeal carcinoma |
title_full |
Development and validation of the immune signature to predict distant metastasis in patients with nasopharyngeal carcinoma |
title_fullStr |
Development and validation of the immune signature to predict distant metastasis in patients with nasopharyngeal carcinoma |
title_full_unstemmed |
Development and validation of the immune signature to predict distant metastasis in patients with nasopharyngeal carcinoma |
title_sort |
development and validation of the immune signature to predict distant metastasis in patients with nasopharyngeal carcinoma |
publisher |
BMJ Publishing Group |
series |
Journal for ImmunoTherapy of Cancer |
issn |
2051-1426 |
publishDate |
2020-06-01 |
description |
BackgroundThe tumor immune microenvironment has clinicopathological significance in predicting prognosis and therapeutic efficacy. We aimed to develop an immune signature to predict distant metastasis in patients with nasopharyngeal carcinoma (NPC).MethodsUsing multiplexed quantitative fluorescence, we detected 17 immune biomarkers in a primary screening cohort of 54 NPC tissues presenting with/without distant metastasis following radical therapy. The LASSO (least absolute shrinkage and selection operator) logistic regression model used statistically significant survival markers in the training cohort (n=194) to build an immune signature. The prognostic and predictive accuracy of it was validated in an external independent group of 304 patients.ResultsEight statistically significant markers were identified in the screening cohort. The immune signature consisting of four immune markers (PD-L1+ CD163+, CXCR5, CD117) in intratumor was adopted to classify patients into high and low risk in the training cohort and it showed a high level of reproducibility between different batches of samples (r=0.988 for intratumor; p<0.0001). High-risk patients had shorter distant metastasis-free survival (HR 5.608, 95% CI 2.619 to 12.006; p<0.0001) and progression-free survival (HR 2.798, 95% CI 1.498 to 5.266; p=0·001). The C-indexes which reflected the predictive capacity in training and validation cohort were 0.703 and 0.636, respectively. Low-risk patients benefited from induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) (HR 0.355, 95% CI 0.147 to 0.857; p=0·021), while high-risk patients did not (HR 1.329, 95% CI 0.543 to 3.253; p=0·533). To predict the individual risk of distant metastasis, nomograms with the integration of both immune signature and clinicopathological risk factors were developed.ConclusionsThe immune signature provided a reliable estimate of distant metastasis risk in patients with NPC and might be applied to identify the cohort which benefit from IC+CCRT. |
url |
https://jitc.bmj.com/content/8/1/e000205.full |
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doaj-bf466c08ee5e46bd8df4c835594488832021-07-19T12:01:21ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-06-018110.1136/jitc-2019-000205Development and validation of the immune signature to predict distant metastasis in patients with nasopharyngeal carcinomaSai-Lan Liu0Li-Juan Bian1Qiu-Yan Chen2Xue-Song Sun3Dong-Hua Luo4Xiao-Yun Li5Bei-Bei Xiao6Jin-Jie Yan7Zi-Jian Lu8Lin-Quan Tang9Hai-Qiang Mai10Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, Guangdong Province, People's Republic of ChinaDepartment of Pathology, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong Province, People's Republic of ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, Guangdong Province, People's Republic of ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, Guangdong Province, People's Republic of ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, Guangdong Province, People's Republic of ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, Guangdong Province, People's Republic of ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, Guangdong Province, People's Republic of ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, Guangdong Province, People's Republic of ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, Guangdong Province, People's Republic of ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, Guangdong Province, People's Republic of ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, Guangdong Province, People's Republic of ChinaBackgroundThe tumor immune microenvironment has clinicopathological significance in predicting prognosis and therapeutic efficacy. We aimed to develop an immune signature to predict distant metastasis in patients with nasopharyngeal carcinoma (NPC).MethodsUsing multiplexed quantitative fluorescence, we detected 17 immune biomarkers in a primary screening cohort of 54 NPC tissues presenting with/without distant metastasis following radical therapy. The LASSO (least absolute shrinkage and selection operator) logistic regression model used statistically significant survival markers in the training cohort (n=194) to build an immune signature. The prognostic and predictive accuracy of it was validated in an external independent group of 304 patients.ResultsEight statistically significant markers were identified in the screening cohort. The immune signature consisting of four immune markers (PD-L1+ CD163+, CXCR5, CD117) in intratumor was adopted to classify patients into high and low risk in the training cohort and it showed a high level of reproducibility between different batches of samples (r=0.988 for intratumor; p<0.0001). High-risk patients had shorter distant metastasis-free survival (HR 5.608, 95% CI 2.619 to 12.006; p<0.0001) and progression-free survival (HR 2.798, 95% CI 1.498 to 5.266; p=0·001). The C-indexes which reflected the predictive capacity in training and validation cohort were 0.703 and 0.636, respectively. Low-risk patients benefited from induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) (HR 0.355, 95% CI 0.147 to 0.857; p=0·021), while high-risk patients did not (HR 1.329, 95% CI 0.543 to 3.253; p=0·533). To predict the individual risk of distant metastasis, nomograms with the integration of both immune signature and clinicopathological risk factors were developed.ConclusionsThe immune signature provided a reliable estimate of distant metastasis risk in patients with NPC and might be applied to identify the cohort which benefit from IC+CCRT.https://jitc.bmj.com/content/8/1/e000205.full |