Prognostic value of novel immune-related genomic biomarkers identified in head and neck squamous cell carcinoma
Background The immune response within the tumor microenvironment plays a key role in tumorigenesis and determines the clinical outcomes of head and neck squamous cell carcinoma (HNSCC). However, to date, a paucity of robust, reliable immune-related biomarkers has been identified that are capable of...
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BMJ Publishing Group
2020-10-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/2/e000444.full |
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| author | Yun Chen Ming Li Yuan Zhang Yao Yao Zhongyi Yan Senlin Lian Liangnian Wei Chao Zhou Dongju Feng Jianrong Yang |
| author_facet | Yun Chen Ming Li Yuan Zhang Yao Yao Zhongyi Yan Senlin Lian Liangnian Wei Chao Zhou Dongju Feng Jianrong Yang |
| author_sort | Yun Chen |
| collection | DOAJ |
| description | Background The immune response within the tumor microenvironment plays a key role in tumorigenesis and determines the clinical outcomes of head and neck squamous cell carcinoma (HNSCC). However, to date, a paucity of robust, reliable immune-related biomarkers has been identified that are capable of estimating prognosis in HNSCC patients.Methods High-throughput RNA sequencing was performed in tumors and matched adjacent tissues from five HNSCC patients, and the immune signatures expression of 730 immune-related transcripts selected from the nCounter PanCancer Immune Profiling Panel were assessed. Survival analyzes were performed in a training cohort, consisting of 416 HNSCC cases, retrieved from The Cancer Genome Atlas (TCGA) database. A prognostic signature was built, using elastic net-penalized Cox regression and backward, stepwise Cox regression analyzes. The outcomes were validated by an independent cohort of 115 HNSCC patients, using tissue microarrays and immunohistochemistry staining. Cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) was also used to estimate the relative fractions of 22 immune-cell types and their correlations coefficients with prognostic biomarkers.Results Collectively, 248 immune-related genes were differentially expressed in paired tumors and normal tissues using RNA sequencing. After process screening in the training TCGA cohort, four immune-related genes (PVR, TNFRSF12A, IL21R, and SOCS1) were significantly associated with overall survival (OS). Integrating these genes with Path_N stage, a multiplex model was built and suggested better performance in determining 5 years OS (receiver operating characteristic (ROC) analysis, area under the curve (AUC)=0.709) than others. Further protein-based validation was conducted in 115 HNSCC patients. Similarly, high expression of PVR and TNFRSF12A were associated with poor OS (Kaplan-Meier p=0.017 and 0.0032), while high expression of IL21R and SOCS1 indicated favorable OS (Kaplan-Meier p<0.0001 and =0.0018). The integrated model with Path_N stage still demonstrated efficacy in OS evaluation (Kaplan-Meier p<0.0001, ROC AUC=0.893). Besides, the four prognostic genes were significantly correlated with activated CD8+ T cells, CD4+ T cells, follicular helper T cells and regulatory T cells, implying the possible involvement of these genes in the immunoregulation and development of HNSCC.Conclusions The well-established model encompassing both immune-related biomarkers and clinicopathological factor might serve as a promising tool for the prognostic prediction of HNSCC. |
| format | Article |
| id | doaj-art-48e7cc98a9c44fe59fe24c633d2fb4ff |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-48e7cc98a9c44fe59fe24c633d2fb4ff2024-11-10T20:30:08ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-10-018210.1136/jitc-2019-000444Prognostic value of novel immune-related genomic biomarkers identified in head and neck squamous cell carcinomaYun Chen0Ming Li1Yuan Zhang2Yao Yao3Zhongyi Yan4Senlin Lian5Liangnian Wei6Chao Zhou7Dongju Feng8Jianrong Yang9The Affiliated Wuxi People`s Hospital of Nanjing Medical University, Wuxi People`s Hospital, Wuxi Medical Center & Department of Immunology, School of Basic Medical Sciences, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, China5 Department of Radiation Oncology, Beijing Hospital/National Center of Gerontology, Beijing, ChinaOphthalmic Center State Key Laboratory of Ophthalmology, Sun Yat-Sen University Zhongshan, Guangzhou, Guangdong, China4China Centre for Health Development Studies, Peking University, Beijing, China2 Department of Immunology, Nanjing Medical University, Nanjing, China2 Department of Immunology, Key Laboratory of Immune Microenvironment and Disease, Nanjing Medical University, Nanjing, China2 Department of Immunology, Key Laboratory of Immune Microenvironment and Disease, Nanjing Medical University, Nanjing, China2 State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China2 Department of Immunology, Key Laboratory of Immune Microenvironment and Disease, Nanjing Medical University, Nanjing, China3 Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Nanjing, ChinaBackground The immune response within the tumor microenvironment plays a key role in tumorigenesis and determines the clinical outcomes of head and neck squamous cell carcinoma (HNSCC). However, to date, a paucity of robust, reliable immune-related biomarkers has been identified that are capable of estimating prognosis in HNSCC patients.Methods High-throughput RNA sequencing was performed in tumors and matched adjacent tissues from five HNSCC patients, and the immune signatures expression of 730 immune-related transcripts selected from the nCounter PanCancer Immune Profiling Panel were assessed. Survival analyzes were performed in a training cohort, consisting of 416 HNSCC cases, retrieved from The Cancer Genome Atlas (TCGA) database. A prognostic signature was built, using elastic net-penalized Cox regression and backward, stepwise Cox regression analyzes. The outcomes were validated by an independent cohort of 115 HNSCC patients, using tissue microarrays and immunohistochemistry staining. Cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) was also used to estimate the relative fractions of 22 immune-cell types and their correlations coefficients with prognostic biomarkers.Results Collectively, 248 immune-related genes were differentially expressed in paired tumors and normal tissues using RNA sequencing. After process screening in the training TCGA cohort, four immune-related genes (PVR, TNFRSF12A, IL21R, and SOCS1) were significantly associated with overall survival (OS). Integrating these genes with Path_N stage, a multiplex model was built and suggested better performance in determining 5 years OS (receiver operating characteristic (ROC) analysis, area under the curve (AUC)=0.709) than others. Further protein-based validation was conducted in 115 HNSCC patients. Similarly, high expression of PVR and TNFRSF12A were associated with poor OS (Kaplan-Meier p=0.017 and 0.0032), while high expression of IL21R and SOCS1 indicated favorable OS (Kaplan-Meier p<0.0001 and =0.0018). The integrated model with Path_N stage still demonstrated efficacy in OS evaluation (Kaplan-Meier p<0.0001, ROC AUC=0.893). Besides, the four prognostic genes were significantly correlated with activated CD8+ T cells, CD4+ T cells, follicular helper T cells and regulatory T cells, implying the possible involvement of these genes in the immunoregulation and development of HNSCC.Conclusions The well-established model encompassing both immune-related biomarkers and clinicopathological factor might serve as a promising tool for the prognostic prediction of HNSCC.https://jitc.bmj.com/content/8/2/e000444.full |
| spellingShingle | Yun Chen Ming Li Yuan Zhang Yao Yao Zhongyi Yan Senlin Lian Liangnian Wei Chao Zhou Dongju Feng Jianrong Yang Prognostic value of novel immune-related genomic biomarkers identified in head and neck squamous cell carcinoma Journal for ImmunoTherapy of Cancer |
| title | Prognostic value of novel immune-related genomic biomarkers identified in head and neck squamous cell carcinoma |
| title_full | Prognostic value of novel immune-related genomic biomarkers identified in head and neck squamous cell carcinoma |
| title_fullStr | Prognostic value of novel immune-related genomic biomarkers identified in head and neck squamous cell carcinoma |
| title_full_unstemmed | Prognostic value of novel immune-related genomic biomarkers identified in head and neck squamous cell carcinoma |
| title_short | Prognostic value of novel immune-related genomic biomarkers identified in head and neck squamous cell carcinoma |
| title_sort | prognostic value of novel immune related genomic biomarkers identified in head and neck squamous cell carcinoma |
| url | https://jitc.bmj.com/content/8/2/e000444.full |
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