{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T10:23:15Z","timestamp":1772274195754,"version":"3.50.1"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T00:00:00Z","timestamp":1683590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072182"],"award-info":[{"award-number":["82072182"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011710","name":"Shaanxi Provincial Science and Technology Department","doi-asserted-by":"publisher","award":["2020SF-179"],"award-info":[{"award-number":["2020SF-179"]}],"id":[{"id":"10.13039\/501100011710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Cutaneous melanoma (CM) is one of the malignant tumors with a relative high lethality. Necroptosis is a novel programmed cell death that participates in anti-tumor immunity and tumor prognosis. Necroptosis has been found to play an important role in tumors like CM. However, the necroptosis-associated lncRNAs\u2019 potential prognostic value in CM has not been identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The RNA sequencing data collected from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Project (GTEx) was utilized to identify differentially expressed genes in CM. By using the univariate Cox regression analysis and machine learning LASSO algorithm, a prognostic risk model had been built depending on 5 necroptosis-associated lncRNAs and was verified by internal validation. The performance of this prognostic model was assessed by the receiver operating characteristic curves. A nomogram was constructed and verified by calibration. Furthermore, we also performed sub-group K-M analysis to explore the 5 lncRNAs\u2019 expression in different clinical stages. Function enrichment had been analyzed by GSEA and ssGSEA. In addition, qRT-PCR was performed to verify the five lncRNAs\u2019 expression level in CM cell line (A2058 and A375) and normal keratinocyte cell line (HaCaT).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We constructed a prognostic model based on five necroptosis-associated lncRNAs (AC245041.1, LINC00665, AC018553.1, LINC01871, and AC107464.3) and divided patients into high-risk group and low-risk group depending on risk scores. A predictive nomogram had been built to be a prognostic indicator to clinical factors. Functional enrichment analysis showed that immune functions had more relationship and immune checkpoints were more activated in low-risk group than that in high-risk group. Thus, the low-risk group would have a more sensitive response to immunotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This risk score signature could be used to divide CM patients into low- and high-risk groups, and facilitate treatment strategy decision making that immunotherapy is more suitable for those in low-risk group, providing a new sight for CM prognostic evaluation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1180732","type":"journal-article","created":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T05:37:35Z","timestamp":1683610655000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Machine learning-based signature of necrosis-associated lncRNAs for prognostic and immunotherapy response prediction in cutaneous melanoma and tumor immune landscape characterization"],"prefix":"10.3389","volume":"14","author":[{"given":"Zhiwei","family":"Cui","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Binyu","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guo","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanan","family":"Gu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baoyan","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jungang","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baoqiang","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22071","article-title":"Whole-genome landscapes of major melanoma subtypes","volume":"545","author":"Hayward","year":"2017","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.790047","article-title":"A novel ferroptosis-related lncRNA prognostic model and immune infiltration features in skin cutaneous melanoma","volume":"9","author":"Sun","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2019.08.002","article-title":"Unraveling the crosstalk between melanoma and immune cells in the tumor microenvironment","volume":"59","author":"Marzagalli","year":"2019","journal-title":"Semin Cancer Biol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.18632\/aging.203982","article-title":"Skin cutaneous melanoma properties of immune-related lncRNAs identifying potential prognostic biomarkers","volume":"14","author":"Ma","year":"2022","journal-title":"Aging (Albany NY)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12583","article-title":"Necroptotic cell death in anti-cancer therapy","volume":"280","author":"Krysko","year":"2017","journal-title":"Immunol Rev"},{"key":"B6","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1186\/s12943-019-1029-8","article-title":"The role of necroptosis in cancer biology and therapy","volume":"18","author":"Gong","year":"2019","journal-title":"Mol Cancer"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2015.56","article-title":"Methylation-dependent loss of RIP3 expression in cancer represses programmed necrosis in response to chemotherapeutics","volume":"25","author":"Koo","year":"2015","journal-title":"Cell Res"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2017.1299302","article-title":"Pro-necrotic molecules impact local immunosurveillance in human breast cancer","volume":"6","author":"Stoll","year":"2017","journal-title":"Oncoimmunology"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.16","article-title":"Differential roles of RIPK1 and RIPK3 in TNF-induced necroptosis and chemotherapeutic agent-induced cell death","volume":"6","author":"Moriwaki","year":"2015","journal-title":"Cell Death Dis"},{"key":"B10","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1038\/s41419-022-04736-6","article-title":"A noncoding regulatory RNA Gm31932 induces cell cycle arrest and differentiation in melanoma via the miR-344d-3-5p\/Prc1 (and Nuf2) axis","volume":"13","author":"Wang","year":"2022","journal-title":"Cell Death Dis"},{"key":"B11","doi-asserted-by":"publisher","first-page":"238","DOI":"10.3892\/or.2021.8189","article-title":"lncRNA TINCR attenuates the proliferation and invasion, and enhances the apoptosis of cutaneous malignant melanoma cells by regulating the miR\u2212424\u22125p\/LATS1 axis","volume":"46","author":"Han","year":"2021","journal-title":"Oncol Rep"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.885391","article-title":"A novel risk model based on autophagy-related LncRNAs predicts prognosis and indicates immune infiltration landscape of patients with cutaneous melanoma","volume":"13","author":"Shu","year":"2022","journal-title":"Front Genet"},{"key":"B13","doi-asserted-by":"publisher","first-page":"120832","DOI":"10.1016\/j.lfs.2022.120832","article-title":"A novel pyroptosis-related LncRNA signature predicts prognosis and indicates tumor immune microenvironment in skin cutaneous melanoma","volume":"307","author":"Zhong","year":"2022","journal-title":"Life Sci"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.1010044","article-title":"Identification and validation of neurotrophic factor-related genes signature in HNSCC to predict survival and immune landscapes","volume":"13","author":"Peng","year":"2022","journal-title":"Front Genet"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27286","article-title":"Melanoma: where we are and where we go","volume":"234","author":"Mohammadpour","year":"2019","journal-title":"J Cell Physiol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2320","DOI":"10.3390\/cells10092320","article-title":"Molecular markers and targets in melanoma","volume":"10","author":"Teixido","year":"2021","journal-title":"Cells"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.28740","article-title":"Autophagy, anoikis, ferroptosis, necroptosis, and endoplasmic reticulum stress: potential applications in melanoma therapy","volume":"234","author":"Ashrafizadeh","year":"2019","journal-title":"J Cell Physiol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"121","DOI":"10.3892\/ol.2020.11983","article-title":"Evodiamine induces reactive oxygen species-dependent apoptosis and necroptosis in human melanoma a-375 cells","volume":"20","author":"Liu","year":"2020","journal-title":"Oncol Lett"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0228015","article-title":"Necroptosis in pancreatic cancer promotes cancer cell migration and invasion by release of CXCL5","volume":"15","author":"Ando","year":"2020","journal-title":"PloS One"},{"key":"B20","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1186\/s13045-020-00946-7","article-title":"Ferroptosis, necroptosis, and pyroptosis in anticancer immunity","volume":"13","author":"Tang","year":"2020","journal-title":"J Hematol Oncol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e20201039","DOI":"10.1084\/jem.20201039","article-title":"Inhibition of ADAM17 impairs endothelial cell necroptosis and blocks metastasis","volume":"219","author":"Bolik","year":"2022","journal-title":"J Exp Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2021.09.003","article-title":"Necroptosis and tumor progression","volume":"8","author":"Yan","year":"2022","journal-title":"Trends Cancer"},{"key":"B23","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.semcancer.2022.07.007","article-title":"Necroptosis pathways in tumorigenesis","volume":"86","author":"Zhang","year":"2022","journal-title":"Semin Cancer Biol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.985051","article-title":"Identification and validation of ferroptosis-related lncRNA signature as a prognostic model for skin cutaneous melanoma","volume":"13","author":"Guo","year":"2022","journal-title":"Front Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.18632\/aging.204151","article-title":"Identification of m7G-associated lncRNA prognostic signature for predicting the immune status in cutaneous melanoma","volume":"14","author":"Rong","year":"2022","journal-title":"Aging (Albany NY)"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1186\/s12885-021-08987-y","article-title":"Angiogenesis-related lncRNAs predict the prognosis signature of stomach adenocarcinoma","volume":"21","author":"Han","year":"2021","journal-title":"BMC Cancer"},{"key":"B27","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1111\/exd.14246","article-title":"Long non-coding RNA LINC00665 promotes melanoma cell growth and migration via regulating the miR-224-5p\/VMA21 axis","volume":"31","author":"Wang","year":"2022","journal-title":"Exp Dermatol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.24630","article-title":"Silencing LINC00665 inhibits cutaneous melanoma in vitro progression and induces apoptosis via the miR-339-3p\/TUBB","volume":"36","author":"Liu","year":"2022","journal-title":"J Clin Lab Anal"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000028553","article-title":"The new horizon of biomarker in melanoma patients: a study based on autophagy-related long non-coding RNA","volume":"101","author":"Li","year":"2022","journal-title":"Med (Baltimore)"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v10.i11.3334","article-title":"Autophagy-related long non-coding RNA prognostic model predicts prognosis and survival of melanoma patients","volume":"10","author":"Qiu","year":"2022","journal-title":"World J Clin cases"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.24384","article-title":"A novel prognostic model associated with the overall survival in patients with breast cancer based on lipid metabolism-related long noncoding RNAs","volume":"36","author":"Shi","year":"2022","journal-title":"J Clin Lab Anal"},{"key":"B32","doi-asserted-by":"publisher","first-page":"7099930","DOI":"10.1155\/2022\/7099930","article-title":"Necroptosis-associated lncRNA prognostic model and clustering analysis: prognosis prediction and tumor-infiltrating lymphocytes in breast cancer","volume":"2022","author":"Tao","year":"2022","journal-title":"J Oncol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16378","article-title":"Identification of autophagy-related long non-coding RNA prognostic signature for breast cancer","volume":"25","author":"Wu","year":"2021","journal-title":"J Cell Mol Med"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fsurg.2021.742360","article-title":"Comprehensive analysis of ferroptosis-related LncRNAs in breast cancer patients reveals prognostic value and relationship with tumor immune microenvironment","volume":"8","author":"Xu","year":"2021","journal-title":"Front Surg"},{"key":"B35","doi-asserted-by":"publisher","first-page":"3436","DOI":"10.3390\/cells11213436","article-title":"Cuprotosis programmed-Cell-Death-Related lncRNA signature predicts prognosis and immune landscape in PAAD patients","volume":"11","author":"Chi","year":"2022","journal-title":"Cells"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1018685","article-title":"Natural killer cell-related prognosis signature characterizes immune landscape and predicts prognosis of HNSCC","volume":"13","author":"Chi","year":"2022","journal-title":"Front Immunol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1172\/JCI69589","article-title":"Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function","volume":"123","author":"Sukumar","year":"2013","journal-title":"J Clin Invest"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.163.1.443","article-title":"In situ T cell responses against melanoma comprise high numbers of locally expanded T cell clonotypes","volume":"163","author":"Thor Straten","year":"1999","journal-title":"J Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-014-1558-3","article-title":"Optimized dendritic cell-based immunotherapy for melanoma: the TriMix-formula","volume":"63","author":"Van Lint","year":"2014","journal-title":"Cancer Immunol Immunother"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2016.06.003","article-title":"Critical role for CD103(+)\/CD141(+) dendritic cells bearing CCR7 for tumor antigen trafficking and priming of T cell immunity in melanoma","volume":"30","author":"Roberts","year":"2016","journal-title":"Cancer Cell"},{"key":"B41","doi-asserted-by":"publisher","first-page":"E9271","DOI":"10.1073\/pnas.1703921114","article-title":"Targeting autophagy inhibits melanoma growth by enhancing NK cells infiltration in a CCL5-dependent manner","volume":"114","author":"Mgrditchian","year":"2017","journal-title":"Proc Natl Acad Sci USA"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01849","article-title":"Arenavirus induced CCL5 expression causes NK cell-mediated melanoma regression","volume":"11","author":"Bhat","year":"2020","journal-title":"Front Immunol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.biomaterials.2016.03.009","article-title":"Targeted delivery of let-7b to reprogramme tumor-associated macrophages and tumor infiltrating dendritic cells for tumor rejection","volume":"90","author":"Huang","year":"2016","journal-title":"Biomaterials"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-0567","article-title":"Genetic evolution of T-cell resistance in the course of melanoma progression","volume":"20","author":"Sucker","year":"2014","journal-title":"Clin Cancer Res"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0060031","article-title":"Co-Stimulation through 4-1BB\/CD137 improves the expansion and function of CD8(+) melanoma tumor-infiltrating lymphocytes for adoptive T-cell therapy","volume":"8","author":"Chacon","year":"2013","journal-title":"PloS One"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2015.1040219","article-title":"Triggering co-stimulation directly in melanoma tumor fragments drives CD8(+) tumor-infiltrating lymphocyte expansion with improved effector-memory properties","volume":"4","author":"Chacon","year":"2015","journal-title":"Oncoimmunology"},{"key":"B47","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1038\/s41568-022-00442-9","article-title":"Mechanisms of immune activation and regulation: lessons from melanoma","volume":"22","author":"Kalaora","year":"2022","journal-title":"Nat Rev Cancer"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1056310","article-title":"Machine learning to construct sphingolipid metabolism genes signature to characterize the immune landscape and prognosis of patients with uveal melanoma","volume":"13","author":"Chi","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1910836","article-title":"Five-year survival with combined nivolumab and ipilimumab in advanced melanoma","volume":"381","author":"Larkin","year":"2019","journal-title":"N Engl J Med"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/ni944","article-title":"BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1","volume":"4","author":"Watanabe","year":"2003","journal-title":"Nat Immunol"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1016\/j.molcel.2018.12.020","article-title":"Ribosomal proteins regulate MHC class I peptide generation for immunosurveillance","volume":"73","author":"Wei","year":"2019","journal-title":"Mol Cell"},{"key":"B52","doi-asserted-by":"publisher","first-page":"e000974","DOI":"10.1136\/jitc-2020-000974","article-title":"Gene signature of antigen processing and presentation machinery predicts response to checkpoint blockade in non-small cell lung cancer (NSCLC) and melanoma","volume":"8","author":"Thompson","year":"2020","journal-title":"J Immunother Cancer"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1900476","article-title":"High GILT expression and an active and intact MHC class II antigen presentation pathway are associated with improved survival in melanoma","volume":"203","author":"Buetow","year":"2019","journal-title":"J Immunol"},{"key":"B54","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.semcancer.2019.07.016","article-title":"Metabolic flexibility in melanoma: a potential therapeutic target","volume":"59","author":"Ruocco","year":"2019","journal-title":"Semin Cancer Biol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1847-2","article-title":"Metabolic heterogeneity confers differences in melanoma metastatic potential","volume":"577","author":"Tasdogan","year":"2020","journal-title":"Nature"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1180732\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T05:37:40Z","timestamp":1683610660000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1180732\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,9]]},"references-count":55,"alternative-id":["10.3389\/fendo.2023.1180732"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2023.1180732","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,9]]},"article-number":"1180732"}}