{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T11:02:37Z","timestamp":1762254157395,"version":"3.40.5"},"reference-count":46,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2022,5,3]],"date-time":"2022-05-03T00:00:00Z","timestamp":1651536000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013314","name":"Higher Education Discipline Innovation Project","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013314","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013313","name":"Overseas Expertise Introduction Project for Discipline Innovation","doi-asserted-by":"publisher","award":["B14035"],"award-info":[{"award-number":["B14035"]}],"id":[{"id":"10.13039\/501100013313","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2017A030312003"],"award-info":[{"award-number":["2017A030312003"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006190","name":"Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>The immune system and hypoxia are major factors influencing radiosensitivity in patients with different cancer types. This study aimed at developing a model to predict radiotherapy response in patients with head and neck squamous cell carcinoma (HNSCC) based on the tumor immune microenvironment and hypoxia signature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>We first evaluated the hypoxia status and tumor immune microenvironment in the Cancer Genome Atlas (TCGA) cohort by using transcriptomic data. Differentially expressed genes (DEGs) were identified between the \u201chigh immunity and low hypoxia\u201d and \u201clow immunity and high hypoxia\u201d groups and those DEGs significantly associated with disease\u2010specific survival in the univariate Cox regression analysis were selected as the prognostic DEGs. We selected the immune hypoxia\u2013related genes (IHRGs) by intersecting prognostic DEGs with immune and hypoxia gene sets. We used the IHRGs to train a multivariate Cox regression model in the TCGA cohort, based on which we calculated the IHRG prognostic index (IHRGPI) for each patient and validated its efficacy in predicting radiotherapy response in the Gene Expression Omnibus cohorts. Furthermore, we explored potential mechanisms and effective combinational treatment strategies for different IHRGPI groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Five IHRGs were used to construct the IHRGPI, which was used to dichotomize the cohorts. The patients with lower IHRGPI showed a better radiotherapy response across different cohorts and endpoints, including overall survival, progression\u2010free survival, and recurrence\u2010free survival (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Patients with higher IHRGPI showed greater hypoxia and lesser immune cell infiltration. A lower IHRGPI indicated a better immunotherapy response, while a higher IHRGPI indicated a better chemotherapy response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>IHRGPI is promising for predicting radiotherapy response and guiding combinational treatment strategies in patients with HNSCC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.4791","type":"journal-article","created":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T05:56:12Z","timestamp":1651643772000},"page":"4673-4687","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Development of a prediction model for radiotherapy response among patients with head and neck squamous cell carcinoma based on the tumor immune microenvironment and hypoxia signature"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5895-1349","authenticated-orcid":false,"given":"Guang\u2010Li","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology Sun Yat\u2010sen 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 P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai\u2010Bin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Sun Yat\u2010sen 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 P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4503-6029","authenticated-orcid":false,"given":"Cheng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Sun Yat\u2010sen 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 P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui\u2010Jia","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Sun Yat\u2010sen 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 P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7605-3609","authenticated-orcid":false,"given":"Wen\u2010Fei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Sun Yat\u2010sen 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 P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1137-9349","authenticated-orcid":false,"given":"Jun","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Sun Yat\u2010sen 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 P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,5,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31937"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2018.09.011"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/09553008914552491"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.2174\/156652409788167087"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11060860"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2009.06.014"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3857\/roj.2020.00136"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-017-0929-y"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.00960"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1507"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0095"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2004088"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.1.207"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056823"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-3322"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr260"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.27"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3612"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-1070-5"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0114-2"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.239244.118"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz446"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0136-1"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-021-01056-8"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-019-1091-2"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0107468"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0360-3016(00)01498-X"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2018.03.007"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.4143\/crt.2017.134"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.12.029"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.10344"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-2345"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.626972"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2021.02.005"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep41138"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.591386"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semradonc.2013.05.002"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1259\/bjr.20130686"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1037"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0039-1687894"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1011165"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21358"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-01048-4"}],"container-title":["Cancer 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