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      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Development and validation of a fourteen- innate immunity-related gene pairs signature for predicting prognosis head and neck squamous cell carcinoma

      research-article
      Author(s): 1 , 2 , 1 , 1 ,
      Publication date (Electronic):
      Journal: BMC Cancer
      Publisher: BioMed Central
      Keywords: TCGA, Bioinformatics, HNSCC, Immune-related gene pairs, Riskscore

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          Abstract

          Background

          Immune-related genes is closely related to the occurrence and prognosis of head and neck squamous cell carcinoma (HNSCC). At the same time, immune-related genes have great potential as prognostic markers in many types of cancer. The prognosis of HNSCC is still poor currently, and it may be effective to predict the clinical outcome of HNSCC by immunogenic analysis.

          Methods

          RNASeq and clinical follow-up information were downloaded from The Cancer Genome Atlas (TCGA), the MINiML format GSE65858 chip expression data was downloaded from NCBI, and immune-related genes was downloaded from the InnateDB database. Immune-related genes in 519 HNSC patients were integrated from TCGA dataset. By using multivariate COX analysis and Lasso regression, robust immune-related gene pairs (IRGPs) that predict clinical outcomes of HNSCC were identified. Finally, a risk prognostic model related to immune gene pair was established and verified by clinical features, test sets and GEO external validation set.

          Results

          A total of 699 IRGPs were significantly correlated with the prognosis of HNSCC patients. Fourteen robust IRGPs were finally obtained by Lasso regression and a prognostic risk prediction model was constructed. Risk score of each sample were calculated based on Risk models and divided into the high-risk group (Risk-H) and low Risk group (Risk-L). Risk models were able to stratify the risk in patients with TNM Stage, Age, gender, and smoking history, and the AUC > 0.65 in training set and test set, shows that 14-IRGPs signature in patients with HNSCC has excellent classification performance. In addition, 14-IRGPs had the highest average C index compared with the prognostic characteristics and T, N, and Age of the 3 previously reported HNSCC.

          Conclusion

          This study constructed 14-IRGPs as a novel prognostic marker for predicting survival in HNSCC patients.

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          Most cited references30

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          Regularization Paths for Generalized Linear Models via Coordinate Descent

          Jerome H. Friedman, Trevor J. Hastie, Robert Tibshirani … (2011)
          Article 0 comments Cited 3228 times – based on 0 reviews     Review now
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            Pan-cancer Immunogenomic Analyses Reveal Genotype-Immunophenotype Relationships and Predictors of Response to Checkpoint Blockade.

            Pornpimol Charoentong, Francesca Finotello, Mihaela Angelova … (2017)
            The Cancer Genome Atlas revealed the genomic landscapes of human cancers. In parallel, immunotherapy is transforming the treatment of advanced cancers. Unfortunately, the majority of patients do not respond to immunotherapy, making the identification of predictive markers and the mechanisms of resistance an area of intense research. To increase our understanding of tumor-immune cell interactions, we characterized the intratumoral immune landscapes and the cancer antigenomes from 20 solid cancers and created The Cancer Immunome Atlas (https://tcia.at/). Cellular characterization of the immune infiltrates showed that tumor genotypes determine immunophenotypes and tumor escape mechanisms. Using machine learning, we identified determinants of tumor immunogenicity and developed a scoring scheme for the quantification termed immunophenoscore. The immunophenoscore was a superior predictor of response to anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) and anti-programmed cell death protein 1 (anti-PD-1) antibodies in two independent validation cohorts. Our findings and this resource may help inform cancer immunotherapy and facilitate the development of precision immuno-oncology.
            Article 0 comments Cited 2119 times – based on 0 reviews     Review now
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              TGF-β attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells

              Sanjeev Mariathasan, Shannon Turley, Dorothee Nickles … (2018)
              Therapeutic antibodies that block the programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1) pathway can induce robust and durable responses in patients with various cancers, including metastatic urothelial cancer (mUC) 1–5 . However, these responses only occur in a subset of patients. Elucidating the determinants of response and resistance is key to improving outcomes and developing new treatment strategies. Here, we examined tumours from a large cohort of mUC patients treated with an anti–PD-L1 agent (atezolizumab) and identified major determinants of clinical outcome. Response was associated with CD8+ T-effector cell phenotype and, to an even greater extent, high neoantigen or tumour mutation burden (TMB). Lack of response was associated with a signature of transforming growth factor β (TGF-β) signalling in fibroblasts, particularly in patients with CD8+ T cells that were excluded from the tumour parenchyma and instead found in the fibroblast- and collagen-rich peritumoural stroma—a common phenotype among patients with mUC. Using a mouse model that recapitulates this immune excluded phenotype, we found that therapeutic administration of a TGF-β blocking antibody together with anti–PD-L1 reduced TGF-β signalling in stromal cells, facilitated T cell penetration into the centre of the tumour, and provoked vigorous anti-tumour immunity and tumour regression. Integration of these three independent biological features provides the best basis for understanding outcome in this setting and suggests that TGF-β shapes the tumour microenvironment to restrain anti-tumour immunity by restricting T cell infiltration.
              Article 0 comments Cited 1908 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Kai Yang: cqfyyk@163.com
                Journal
                Journal ID (nlm-ta): BMC Cancer
                Journal ID (iso-abbrev): BMC Cancer
                Title: BMC Cancer
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1471-2407
                Publication date (Electronic): 20 October 2020
                Publication date PMC-release: 20 October 2020
                Publication date Collection: 2020
                Volume: 20
                Electronic Location Identifier: 1015
                Affiliations
                [1 ]GRID grid.452206.7, Department of Oral and Maxillofacial Surgery, , the First Affiliated Hospital of Chongqing Medical University, ; No 1. Youyi Road, Yuzhong District, Chongqing, 400016 China
                [2 ]GRID grid.452206.7, Department of Pharmacy, , the First Affiliated Hospital of Chongqing Medical University, ; Chongqing, 400016 China
                Article
                Publisher ID: 7489
                DOI: 10.1186/s12885-020-07489-7
                PMC ID: 7574345
                PubMed ID: 33081731
                SO-VID: 9d01bf2d-b2f6-44ec-aa58-bd719c0e0926
                Copyright © © The Author(s) 2020
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                Date received : 12 June 2020
                Date accepted : 2 October 2020
                Categories
                Subject: Research Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2020

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: tcga,bioinformatics,hnscc,immune-related gene pairs,riskscore
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: tcga, bioinformatics, hnscc, immune-related gene pairs, riskscore

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