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      An angiogenesis-associated gene-based signature predicting prognosis and immunotherapy efficacy of head and neck squamous cell carcinoma patients

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          Abstract

          Objectives

          To develop a model that can assist in the diagnosis and prediction of prognosis for head and neck squamous cell carcinoma (HNSCC).

          Materials and methods

          Data from TCGA and GEO databases were used to generate normalized gene expression data. Consensus Cluster Plus was used for cluster analysis and the relationship between angiogenesis-associated gene (AAG) expression patterns, clinical characteristics and survival was examined. Support vector machine (SVM) and least absolute shrinkage and selection operator (LASSO) analyzes and multiple logistic regression analyzes were performed to determine the diagnostic model, and a prognostic nomogram was constructed using univariate and multivariate Cox regression analyses. ESTIMATE, XCELL, TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT-ABS, CIBERSORT algorithms were used to assess the immune microenvironment of HNSCC patients. In addition, gene set enrichment analysis, treatment sensitivity analysis, and AAGs mutation studies were performed. Finally, we also performed immunohistochemistry (IHC) staining in the tissue samples.

          Results

          We classified HNSCC patients into subtypes based on differences in AAG expression from TCGA and GEO databases. There are differences in clinical features, TME, and immune-related gene expression between two subgroups. We constructed a HNSCC diagnostic model based on nine AAGs, which has good sensitivity and specificity. After further screening, we constructed a prognostic risk signature for HNSCC based on six AAGs. The constructed risk score had a good independent prognostic significance, and it was further constructed into a prognostic nomogram together with age and stage. Different prognostic risk groups have differences in immune microenvironment, drug sensitivity, gene enrichment and gene mutation.

          Conclusion

          We have constructed a diagnostic and prognostic model for HNSCC based on AAG, which has good performance. The constructed prognostic risk score is closely related to tumor immune microenvironment and immunotherapy response.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s00432-024-05606-8.

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          Most cited references46

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          Hallmarks of Cancer: The Next Generation

          The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods

            Estimates of the worldwide incidence and mortality from 36 cancers and for all cancers combined for the year 2018 are now available in the GLOBOCAN 2018 database, compiled and disseminated by the International Agency for Research on Cancer (IARC). This paper reviews the sources and methods used in compiling the cancer statistics in 185 countries. The validity of the national estimates depends upon the representativeness of the source information, and to take into account possible sources of bias, uncertainty intervals are now provided for the estimated sex- and site-specific all-ages number of new cancer cases and cancer deaths. We briefly describe the key results globally and by world region. There were an estimated 18.1 million (95% UI: 17.5-18.7 million) new cases of cancer (17 million excluding non-melanoma skin cancer) and 9.6 million (95% UI: 9.3-9.8 million) deaths from cancer (9.5 million excluding non-melanoma skin cancer) worldwide in 2018.
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              Microenvironmental regulation of tumor progression and metastasis.

              Cancers develop in complex tissue environments, which they depend on for sustained growth, invasion and metastasis. Unlike tumor cells, stromal cell types within the tumor microenvironment (TME) are genetically stable and thus represent an attractive therapeutic target with reduced risk of resistance and tumor recurrence. However, specifically disrupting the pro-tumorigenic TME is a challenging undertaking, as the TME has diverse capacities to induce both beneficial and adverse consequences for tumorigenesis. Furthermore, many studies have shown that the microenvironment is capable of normalizing tumor cells, suggesting that re-education of stromal cells, rather than targeted ablation per se, may be an effective strategy for treating cancer. Here we discuss the paradoxical roles of the TME during specific stages of cancer progression and metastasis, as well as recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects.
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                Author and article information

                Contributors
                lin2007512@vip.163.com
                zhanglei6551@126.com
                shaowei@ahmu.edu.cn
                Journal
                J Cancer Res Clin Oncol
                J Cancer Res Clin Oncol
                Journal of Cancer Research and Clinical Oncology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0171-5216
                1432-1335
                12 February 2024
                12 February 2024
                2024
                : 150
                : 2
                : 91
                Affiliations
                [1 ]College & Hospital of Stomatology, Key Lab. of Oral Diseases Research of Anhui Province, Anhui Medical University, ( https://ror.org/03xb04968) Hefei, China
                [2 ]The First Affiliated Hospital (First Clinical Medical College), Anhui Medical University, ( https://ror.org/03xb04968) Hefei, China
                [3 ]GRID grid.254250.4, ISNI 0000 0001 2264 7145, CUNY School of Medicine, ; New York, USA
                [4 ]GRID grid.413734.6, ISNI 0000 0000 8499 1112, Division of Oral and Maxillofacial Surgery, , NewYork Presbyterian (Columbia Irving Medical Center), ; New York, USA
                [5 ]UK Program Site, American University of the Caribbean School of Medicine, Preston, UK
                [6 ]Bronxcare Health System, New York, USA
                [7 ]GRID grid.452696.a, ISNI 0000 0004 7533 3408, The Second Affiliated Hospital of Anhui Medical University, ; Hefei, China
                [8 ]GRID grid.186775.a, ISNI 0000 0000 9490 772X, The Affiliated Chuzhou Hospital of Anhui Medical University, The First People’s Hospital of Chuzhou, ; Chuzhou, China
                [9 ]Department of Microbiology and Parasitology (Anhui Provincial Laboratory of Pathogen Biology), School of Basic Medical Sciences, Anhui Medical University, ( https://ror.org/03xb04968) Hefei, China
                Article
                5606
                10.1007/s00432-024-05606-8
                10861726
                38347320
                b488c6a2-6fff-4ed4-b150-335852d3b138
                © The Author(s) 2024

                Open Access This 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/.

                History
                : 17 September 2023
                : 2 January 2024
                Funding
                Funded by: Anhui Provincial Natural Science Foundation
                Award ID: 2008085QH371
                Award Recipient :
                Funded by: Research Level Improvement Project of Anhui Medical University
                Award ID: 2021xkjT001
                Award Recipient :
                Funded by: National Natural Science Foundation of China
                Award ID: 82071770
                Award Recipient :
                Funded by: Scientific Research of BSKY in Anhui Medical University
                Award ID: XJ201601
                Award Recipient :
                Categories
                Research
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2024

                Oncology & Radiotherapy
                angiogenesis-associated gene,hnscc,diagnosis,prognostic signature,immunotherapy

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