{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T06:41:37Z","timestamp":1769755297299,"version":"3.49.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T00:00:00Z","timestamp":1670889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Immunogenic cell death (ICD) is a form of regulated cell death that elicits immune response. Common inducers of ICD include cancer chemotherapy and radiation therapy. A better understanding of ICD might contribute to modify the current regimens of anti-cancer therapy, especially immunotherapy. This study aimed to identify ICD-related prognostic gene signatures in breast cancer (BC). An ICD-based gene prognostic signature was developed using Lasso-cox regression and Kaplan-Meier survival analysis based on datasets acquired from the Cancer Genome Atlas and Gene Expression Omnibus. A nomogram model was developed to predict the prognosis of BC patients. Gene Set Enrichment Analysis (GESA) and Gene Set Variation Analysis (GSVA) were used to explore the differentially expressed signaling pathways in high and low-risk groups. CIBERSORT and ESTIMATE algorithms were performed to investigate the difference of immune status in tumor microenvironment of different risk groups. Six genes (<jats:italic>CALR<\/jats:italic>, <jats:italic>CLEC9A<\/jats:italic>, <jats:italic>BAX<\/jats:italic>, <jats:italic>TLR4<\/jats:italic>, <jats:italic>CXCR3<\/jats:italic>, and <jats:italic>PIK3CA<\/jats:italic>) were selected for construction and validation of the prognosis model of BC based on public data. GSEA and GSVA analysis found that immune-related gene sets were enriched in low-risk group. Moreover, immune cell infiltration analysis showed that the immune features of the high-risk group were characterized by higher infiltration of tumor-associated macrophages and a lower proportion of CD8<jats:sup>+<\/jats:sup> T cells, suggesting an immune evasive tumor microenvironment. We constructed and validated an ICD-based gene signature for predicting prognosis of breast cancer patients. Our model provides a tool with good discrimination and calibration abilities to predict the prognosis of BC, especially triple-negative breast cancer (TNBC).<\/jats:p>","DOI":"10.3389\/fgene.2022.1069921","type":"journal-article","created":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T05:41:33Z","timestamp":1670910093000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Construction of an immunogenic cell death-based risk score prognosis model in breast cancer"],"prefix":"10.3389","volume":"13","author":[{"given":"Yanling","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianyuan","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingcui","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyuan","family":"Rong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weilun","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunqiang","family":"Duan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anbang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianshui","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiarui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhang","family":"Shang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiyun","family":"Zou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baoliang","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2274","DOI":"10.2174\/0929867328666210811145043","article-title":"LPS\/TLR4 pathways in breast cancer: Insights into cell signalling","volume":"29","author":"Afroz","year":"2022","journal-title":"Curr. Med. Chem."},{"key":"B2","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1093\/oxfordjournals.annonc.a010538","article-title":"Expression of Bax in relation to Bcl-2 and other predictive parameters in breast cancer","volume":"7","author":"Binder","year":"1996","journal-title":"Ann. Oncol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.celrep.2016.12.019","article-title":"Pan-cancer immunogenomic analyses reveal genotype-immunophenotype relationships and predictors of response to checkpoint blockade","volume":"18","author":"Charoentong","year":"2017","journal-title":"Cell Rep."},{"key":"B4","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.ccell.2017.11.019","article-title":"TIM-3 regulates CD103+ dendritic cell function and response to chemotherapy in breast cancer","volume":"33","author":"De Mingo Pulido","year":"2018","journal-title":"Cancer Cell"},{"key":"B5","doi-asserted-by":"publisher","first-page":"28","DOI":"10.3322\/canjclin.47.1.28","article-title":"Tumor-related prognostic factors for breast cancer","volume":"47","author":"Donegan","year":"1997","journal-title":"Ca. Cancer J. Clin."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2342","DOI":"10.1200\/JCO.2010.31.6950","article-title":"Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer: Clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype--ACOSOG Z1031","volume":"29","author":"Ellis","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2350","DOI":"10.1002\/cam4.827","article-title":"Prognostic value of HMGB1 in early breast cancer patients under neoadjuvant chemotherapy","volume":"5","author":"Exner","year":"2016","journal-title":"Cancer Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/nri.2016.107","article-title":"Immunogenic cell death in cancer and infectious disease","volume":"17","author":"Galluzzi","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1038\/s41571-020-0413-z","article-title":"Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors","volume":"17","author":"Galluzzi","year":"","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e000337","DOI":"10.1136\/jitc-2019-000337","article-title":"Consensus guidelines for the definition, detection and interpretation of immunogenic cell death","volume":"8","author":"Galluzzi","year":"","journal-title":"J. Immunother. Cancer"},{"key":"B11","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.immuni.2019.12.018","article-title":"Tumor immunology and tumor evolution: Intertwined histories","volume":"52","author":"Galon","year":"2020","journal-title":"Immunity"},{"key":"B12","doi-asserted-by":"publisher","first-page":"i104","DOI":"10.1136\/ard.2010.140145","article-title":"Inflammatory cytokines in cancer: Tumour necrosis factor and interleukin 6 take the stage","volume":"70","author":"Grivennikov","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"B13","doi-asserted-by":"publisher","first-page":"5668","DOI":"10.1038\/s41467-021-25962-0","article-title":"Spatial immunophenotypes predict response to anti-PD1 treatment and capture distinct paths of T cell evasion in triple negative breast cancer","volume":"12","author":"Hammerl","year":"2021","journal-title":"Nat. Commun."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1038\/s41591-018-0136-1","article-title":"Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response","volume":"24","author":"Jiang","year":"2018","journal-title":"Nat. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1038\/s41590-022-01132-2","article-title":"Immunogenic cell stress and death","volume":"23","author":"Kroemer","year":"2022","journal-title":"Nat. Immunol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1038\/nrc3380","article-title":"Immunogenic cell death and DAMPs in cancer therapy","volume":"12","author":"Krysko","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1038\/modpathol.2010.173","article-title":"Clinicopathological significance of calreticulin in breast invasive ductal carcinoma","volume":"23","author":"Lwin","year":"2010","journal-title":"Mod. Pathol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1186\/s40425-018-0479-7","article-title":"High and low mutational burden tumors versus immunologically hot and cold tumors and response to immune checkpoint inhibitors","volume":"6","author":"Maleki Vareki","year":"2018","journal-title":"J. Immunother. Cancer"},{"key":"B19","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1093\/jnci\/djz068","article-title":"Expected monetary impact of oncotype DX score-concordant systemic breast cancer therapy based on the TAILORx trial","volume":"112","author":"Mariotto","year":"2020","journal-title":"J. Natl. Cancer Inst."},{"key":"B20","doi-asserted-by":"publisher","first-page":"4809","DOI":"10.1158\/0008-5472.CAN-11-0753","article-title":"Pivotal role of innate and adaptive immunity in anthracycline chemotherapy of established tumors","volume":"71","author":"Mattarollo","year":"2011","journal-title":"Cancer Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1001\/jamaoncol.2019.6650","article-title":"Effect of Pembrolizumab plus neoadjuvant chemotherapy on pathologic Complete response in women with early-stage breast cancer: An analysis of the ongoing phase 2 adaptively randomized I-SPY2 trial","volume":"6","author":"Nanda","year":"2020","journal-title":"JAMA Oncol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"2128","DOI":"10.1016\/S0140-6736(18)30789-X","article-title":"International validation of the consensus Immunoscore for the classification of colon cancer: A prognostic and accuracy study","volume":"391","author":"Pag\u00e8S","year":"2018","journal-title":"Lancet (London, Engl."},{"key":"B23","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1038\/s41571-020-0388-9","article-title":"Personalized early detection and prevention of breast cancer: ENVISION consensus statement","volume":"17","author":"Pashayan","year":"2020","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/s41577-021-00574-3","article-title":"CD8+ T cell differentiation and dysfunction in cancer","volume":"22","author":"Philip","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1172\/JCI40269","article-title":"Chemotherapy enhances tumor cell susceptibility to CTL-mediated killing during cancer immunotherapy in mice","volume":"120","author":"Ramakrishnan","year":"2010","journal-title":"J. Clin. Invest."},{"key":"B26","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1016\/j.annonc.2020.01.072","article-title":"Pembrolizumab plus chemotherapy as neoadjuvant treatment of high-risk, early-stage triple-negative breast cancer: Results from the phase 1b open-label, multicohort KEYNOTE-173 study","volume":"31","author":"Schmid","year":"2020","journal-title":"Ann. Oncol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"Ca. Cancer J. Clin."},{"key":"B28","doi-asserted-by":"publisher","first-page":"x12","DOI":"10.1093\/annonc\/mdz381","article-title":"Efficacy of PI3K inhibitors in advanced breast cancer","volume":"30","author":"Verret","year":"2019","journal-title":"Ann. Oncol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"870914","DOI":"10.3389\/fonc.2022.870914","article-title":"Immunogenic cell death-relevant damage-associated molecular patterns and sensing receptors in triple-negative breast cancer molecular subtypes and implications for immunotherapy","volume":"12","author":"Xu","year":"2022","journal-title":"Front. Oncol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"Omics a J. Integr. Biol."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.1069921\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T05:41:36Z","timestamp":1670910096000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.1069921\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,13]]},"references-count":30,"alternative-id":["10.3389\/fgene.2022.1069921"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2022.1069921","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,13]]},"article-number":"1069921"}}