{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T02:16:03Z","timestamp":1763950563497,"version":"3.41.2"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32370921"],"award-info":[{"award-number":["32370921"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Melanoma, caused by malignant melanocytes, is known for its invasiveness and poor prognosis. Therapies are often ineffective due to their heterogeneity and resistance. Bacillus Calmette-Gu\u00e9rin (BCG), primarily a tuberculosis vaccine, shows potential in treating melanoma by activating immune responses. In this study, data from The Cancer Genome Atlas and the National Center for Biotechnology Information Gene Expression Omnibus database were utilized to determine pivotal DEGs such as DSC2, CXCR1, BOK, and CSTB, which are significantly upregulated in BCG-treated blood samples and are strongly associated with the prognosis of melanoma. We employ tools like edgeR and ggplot2 for functional and pathway analysis and develop a prognostic model using LASSO Cox regression analysis to predict patient survival. A notable finding is the correlation between BCG-related genes and immune cell infiltration in melanoma, highlighting the potential of these genes as both biomarkers and therapeutic targets. Additionally, the study examines genetic alterations in these genes and their impact on the disease. This study highlights the necessity of further exploring BCG-related genes for insights into melanoma pathogenesis and treatment enhancement, suggesting that BCG's role in immune activation could offer novel therapeutic avenues in cancer treatment.<\/jats:p>","DOI":"10.1093\/jleuko\/qiae064","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T20:11:45Z","timestamp":1710360705000},"source":"Crossref","is-referenced-by-count":2,"title":["Specific BCG-related gene expression levels correlate with immune cell infiltration and prognosis in melanoma"],"prefix":"10.1093","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9266-3834","authenticated-orcid":false,"given":"He","family":"Ren","sequence":"first","affiliation":[{"name":"Department of Breast Surgery, Harbin Medical University Cancer Hospital , 150 Haping Rd, Harbin, 150081, Heilongjiang ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiacheng","family":"He","sequence":"additional","affiliation":[{"name":"College of Environment and Chemistry Engineering, Yanshan University , 438 W Hebei Rd, Qinhuangdao, 066004, Hebei ,","place":["China"]},{"name":"Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University , 601 W Huangpu Ave, Guangzhou, 510632, Guangdong ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Guangzhou Twelfth People's Hospital , 1 Tianqiang Rd, Guangzhou, 510620, Guangdong ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoqian","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Measurement Technology and Instrumentation of Hebei Province , 438 W Hebei Rd, Qinhuangdao, 066004, Hebei ,","place":["China"]},{"name":"School of Electrical Engineering, Yanshan University , 438 W Hebei Rd, Qinhuangdao, 066004, Hebei ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4600-3082","authenticated-orcid":false,"given":"Jianlei","family":"Hao","sequence":"additional","affiliation":[{"name":"Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University , 601 W Huangpu Ave, Guangzhou, 510632, Guangdong ,","place":["China"]},{"name":"Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital Affiliated with Jinan University, Jinan University , 79 Kangning Rd, Zhuhai, 519000, Guangdong ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Han","sequence":"additional","affiliation":[{"name":"School of Health, Guangdong Pharmaceutical University , 280 Daxuecheng Outer Ring East Rd, Guangzhou, 510006, Guangdong ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,3,13]]},"reference":[{"issue":"1","key":"2025010619021302400_qiae064-B1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3322\/caac.21820","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J Clin"},{"issue":"6","key":"2025010619021302400_qiae064-B2","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1038\/s41568-023-00565-7","article-title":"The journey from melanocytes to melanoma","volume":"23","author":"Centeno","year":"2023","journal-title":"Nat Rev Cancer"},{"issue":"6375","key":"2025010619021302400_qiae064-B3","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1126\/science.aao4572","article-title":"Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy","volume":"359","author":"Chowell","year":"2018","journal-title":"Science"},{"issue":"5","key":"2025010619021302400_qiae064-B4","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1016\/s1470-2045(18)30142-6","article-title":"Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (Columbus): a multicentre, open-label, randomised phase 3 trial","volume":"19","author":"Dummer","year":"2018","journal-title":"Lancet Oncol"},{"issue":"20","key":"2025010619021302400_qiae064-B5","doi-asserted-by":"publisher","first-page":"1867","DOI":"10.1056\/NEJMoa1408868","article-title":"Combined vemurafenib and cobimetinib in BRAF-mutated melanoma","volume":"371","author":"Larkin","year":"2014","journal-title":"N Engl J Med"},{"key":"2025010619021302400_qiae064-B6","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.ejca.2016.04.005","article-title":"Resistance to combination BRAF and MEK inhibition in metastatic melanoma: where to next?","volume":"62","author":"Welsh","year":"2016","journal-title":"Eur J Cancer"},{"issue":"1","key":"2025010619021302400_qiae064-B7","doi-asserted-by":"publisher","first-page":"e2","DOI":"10.1016\/s1473-3099(21)00403-5","article-title":"100 yr of Mycobacterium bovis Bacille Calmette-Gu\u00e9rin","volume":"22","author":"Lange","year":"2022","journal-title":"Lancet Infect Dis"},{"issue":"3","key":"2025010619021302400_qiae064-B8","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/nrurol.2014.15","article-title":"The mechanism of action of BCG therapy for bladder cancer\u2013a current perspective","volume":"11","author":"Redelman-Sidi","year":"2014","journal-title":"Nat Rev Urol"},{"issue":"1","key":"2025010619021302400_qiae064-B9","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.molimm.2015.06.019","article-title":"Trained immunity: a smart way to enhance innate immune defence","volume":"68","author":"van der Meer","year":"2015","journal-title":"Mol Immunol"},{"issue":"1","key":"2025010619021302400_qiae064-B10","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1186\/s12967-023-03944-8","article-title":"BCG-induced trained immunity: history, mechanisms and potential applications","volume":"21","author":"Chen","year":"2023","journal-title":"J Transl Med"},{"issue":"3","key":"2025010619021302400_qiae064-B11","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.eururo.2020.02.012","article-title":"Systematic review of the therapeutic efficacy of bladder-preserving treatments for non-muscle-invasive bladder cancer following intravesical Bacillus Calmette-Gu\u00e9rin","volume":"78","author":"Li","year":"2020","journal-title":"Eur Urol"},{"key":"2025010619021302400_qiae064-B12","doi-asserted-by":"publisher","first-page":"1160269","DOI":"10.3389\/fonc.2023.1160269","article-title":"Abscopal responses in patients with metastatic melanoma involving skin and subcutaneous tissues treated with intralesional il2 plus BCG","volume":"13","author":"Vidovic","year":"2023","journal-title":"Front Oncol"},{"key":"2025010619021302400_qiae064-B13","doi-asserted-by":"publisher","first-page":"2806","DOI":"10.3389\/fimmu.2019.02806","article-title":"BCG-induced cross-protection and development of trained immunity: implication for vaccine design","volume":"10","author":"Covi\u00e1n","year":"2019","journal-title":"Front Immunol"},{"issue":"1","key":"2025010619021302400_qiae064-B14","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1038\/s41598-017-18528-y","article-title":"Mycobacterium tuberculosis exploits a molecular off switch of the immune system for intracellular survival","volume":"8","author":"von Both","year":"2018","journal-title":"Sci Rep"},{"key":"2025010619021302400_qiae064-B15","doi-asserted-by":"publisher","first-page":"e108","DOI":"10.1158\/0008-5472.Can-17-0307","article-title":"Timer: a web server for comprehensive analysis of tumor-infiltrating immune cells","volume":"77","author":"Li","year":"2017","journal-title":"Cancer Res"},{"issue":"20","key":"2025010619021302400_qiae064-B16","doi-asserted-by":"publisher","first-page":"4200","DOI":"10.1093\/bioinformatics\/btz210","article-title":"TISIDB: an integrated repository portal for tumor-immune system interactions","volume":"35","author":"Ru","year":"2019","journal-title":"Bioinformatics"},{"issue":"23","key":"2025010619021302400_qiae064-B17","doi-asserted-by":"publisher","first-page":"3861","DOI":"10.1158\/0008-5472.Can-23-0816","article-title":"Analysis and visualization of longitudinal genomic and clinical data from the AACR project genie biopharma collaborative in cbioportal","volume":"83","author":"de Bruijn","year":"2023","journal-title":"Cancer Res"},{"issue":"2","key":"2025010619021302400_qiae064-B18","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1189\/jlb.5RI0116-013RR","article-title":"Combinatorial approach to cancer immunotherapy: strength in numbers","volume":"100","author":"Vilgelm","year":"2016","journal-title":"J Leukoc Biol"},{"issue":"9","key":"2025010619021302400_qiae064-B19","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1038\/ng.2359","article-title":"Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma","volume":"44","author":"Krauthammer","year":"2012","journal-title":"Nat Genet"},{"issue":"1","key":"2025010619021302400_qiae064-B20","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1158\/2159-8290.CD-13-0617","article-title":"The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma","volume":"4","author":"Van Allen","year":"2014","journal-title":"Cancer Discov"},{"issue":"10151","key":"2025010619021302400_qiae064-B21","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/s0140-6736(18)31559-9","article-title":"Melanoma","volume":"392","author":"Schadendorf","year":"2018","journal-title":"Lancet"},{"key":"2025010619021302400_qiae064-B22","doi-asserted-by":"publisher","first-page":"86","DOI":"10.3389\/fonc.2018.00086","article-title":"Anti-PD-1 and anti-CTLA-4 therapies in cancer: mechanisms of action, efficacy, and limitations","volume":"8","author":"Seidel","year":"2018","journal-title":"Front Oncol"},{"key":"2025010619021302400_qiae064-B23","doi-asserted-by":"publisher","first-page":"880876","DOI":"10.3389\/fonc.2022.880876","article-title":"Mechanisms of immunotherapy resistance in cutaneous melanoma: recognizing a shapeshifter","volume":"12","author":"Thornton","year":"2022","journal-title":"Front Oncol"},{"issue":"6","key":"2025010619021302400_qiae064-B24","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1111\/joim.13037","article-title":"Clinical and molecular insights into BCG immunotherapy for melanoma","volume":"288","author":"Kremenovic","year":"2020","journal-title":"J Intern Med"},{"issue":"1","key":"2025010619021302400_qiae064-B25","doi-asserted-by":"publisher","first-page":"2160094","DOI":"10.1080\/2162402x.2022.2160094","article-title":"BCG-activation of leukocytes is sufficient for the generation of donor-independent innate anti-tumor NK and \u03b3\u03b4 t-cells that can be further expanded in vitro","volume":"12","author":"Esteso","year":"2023","journal-title":"Oncoimmunology"},{"key":"2025010619021302400_qiae064-B26","doi-asserted-by":"publisher","first-page":"109208","DOI":"10.1016\/j.clim.2022.109208","article-title":"The impact of BCG dose and revaccination on trained immunity","volume":"246","author":"Debisarun","year":"2023","journal-title":"Clin Immunol"},{"issue":"19","key":"2025010619021302400_qiae064-B27","doi-asserted-by":"publisher","first-page":"1980","DOI":"10.1001\/jama.2020.17598","article-title":"Bladder cancer: a review","volume":"324","author":"Lenis","year":"2020","journal-title":"JAMA"},{"issue":"40","key":"2025010619021302400_qiae064-B28","doi-asserted-by":"publisher","first-page":"eabg7265","DOI":"10.1126\/sciadv.abg7265","article-title":"Desmosomal proteins of DSC2 and PKP1 promote cancer cells survival and metastasis by increasing cluster formation in circulatory system","volume":"7","author":"Li","year":"2021","journal-title":"Sci Adv"},{"issue":"3","key":"2025010619021302400_qiae064-B29","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1002\/path.4583","article-title":"Integrated genomic and transcriptomic analysis of human brain metastases identifies alterations of potential clinical significance","volume":"237","author":"Saunus","year":"2015","journal-title":"J Pathol"},{"key":"2025010619021302400_qiae064-B30","doi-asserted-by":"publisher","first-page":"645623","DOI":"10.3389\/fonc.2021.645623","article-title":"Pulmonary neuroendocrine neoplasms overexpressing epithelial-mesenchymal transition mechanical barriers genes lack immune-suppressive response and present an increased risk of metastasis","volume":"11","author":"Prieto","year":"2021","journal-title":"Front Oncol"},{"issue":"3","key":"2025010619021302400_qiae064-B31","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1189\/jlb.0208125","article-title":"The functional significance behind expressing two il-8 receptor types on pmn","volume":"86","author":"Stillie","year":"2009","journal-title":"J Leukoc Biol"},{"issue":"10","key":"2025010619021302400_qiae064-B32","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1038\/s41416-021-01310-3","article-title":"Checkpoint-blocker-induced autoimmunity is associated with favourable outcome in metastatic melanoma and distinct t-cell expression profiles","volume":"124","author":"Ye","year":"2021","journal-title":"Br J Cancer"},{"issue":"12","key":"2025010619021302400_qiae064-B33","doi-asserted-by":"publisher","first-page":"2682","DOI":"10.1038\/s41418-019-0327-4","article-title":"Bok regulates mitochondrial fusion and morphology","volume":"26","author":"Schulman","year":"2019","journal-title":"Cell Death Differ"},{"issue":"6","key":"2025010619021302400_qiae064-B34","doi-asserted-by":"publisher","first-page":"1366","DOI":"10.1038\/sj.jid.5700192","article-title":"Loss of proapoptotic BCL-2-related multidomain proteins in primary melanomas is associated with poor prognosis","volume":"126","author":"Fecker","year":"2006","journal-title":"J Invest Dermatol"},{"issue":"9","key":"2025010619021302400_qiae064-B35","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1038\/s41388-021-02161-1","article-title":"The BCL-2 family member BOK promotes KRAS-driven lung cancer progression in a p53-dependent manner","volume":"41","author":"Meinhardt","year":"2022","journal-title":"Oncogene"},{"issue":"15","key":"2025010619021302400_qiae064-B36","doi-asserted-by":"publisher","first-page":"2213","DOI":"10.1242\/jcs.181727","article-title":"Bok is a genuine multi-BH-domain protein that triggers apoptosis in the absence of bax and bak","volume":"129","author":"Einsele-Scholz","year":"2016","journal-title":"J Cell Sci"},{"issue":"12","key":"2025010619021302400_qiae064-B37","doi-asserted-by":"publisher","first-page":"e1126","DOI":"10.1002\/ctm2.1126","article-title":"Cystatin b increases autophagic flux by sustaining proteolytic activity of cathepsin b and fuels glycolysis in pancreatic cancer: CSTB orchestrates autophagy and glycolysis in PDAC","volume":"12","author":"Jiang","year":"2022","journal-title":"Clin Transl Med"},{"key":"2025010619021302400_qiae064-B38","doi-asserted-by":"publisher","first-page":"1176572","DOI":"10.3389\/fonc.2023.1176572","article-title":"Identification of a novel signature based on macrophage-related marker genes to predict prognosis and immunotherapeutic effects in hepatocellular carcinoma","volume":"13","author":"Su","year":"2023","journal-title":"Front Oncol"},{"issue":"6","key":"2025010619021302400_qiae064-B39","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1016\/j.bone.2012.08.123","article-title":"Thickened skull, scoliosis and other skeletal findings in unverricht-lundborg disease link cystatin b function to bone metabolism","volume":"51","author":"Suoranta","year":"2012","journal-title":"Bone"},{"issue":"4","key":"2025010619021302400_qiae064-B40","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":"2025010619021302400_qiae064-B41","doi-asserted-by":"publisher","first-page":"245.212","DOI":"10.4049\/jimmunol.210.Supp.245.12","article-title":"Innate and adaptive mechanisms induced by BCG immunotherapy in melanoma murine model","volume":"210","author":"de Queiroz","year":"2023","journal-title":"J Immunol"},{"issue":"8","key":"2025010619021302400_qiae064-B42","doi-asserted-by":"publisher","first-page":"1998","DOI":"10.3390\/cancers14081998","article-title":"T-cells expressing a highly potent prame-specific t-cell receptor in combination with a chimeric pd1-41bb co-stimulatory receptor show a favorable preclinical safety profile and strong anti-tumor reactivity","volume":"14","author":"Sailer","year":"2022","journal-title":"Cancers (Basel)"},{"issue":"8","key":"2025010619021302400_qiae064-B43","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1038\/s41423-023-01017-w","article-title":"A novel role for mitochondrial fission in macrophages: trained innate immunity induced by beta-glucan","volume":"20","author":"Brichkina","year":"2023","journal-title":"Cell Mol Immunol"},{"key":"2025010619021302400_qiae064-B44","doi-asserted-by":"publisher","first-page":"605767","DOI":"10.3389\/fgene.2020.605767","article-title":"The construction and analysis of tumor-infiltrating immune cells and cerna networks in bladder cancer","volume":"11","author":"Jiang","year":"2020","journal-title":"Front Genet"},{"issue":"6","key":"2025010619021302400_qiae064-B45","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1158\/1078-0432.Ccr-19-2625","article-title":"Inhibition of mdsc trafficking with sx-682, a cxcr1\/2 inhibitor, enhances NK-cell immunotherapy in head and neck cancer models","volume":"26","author":"Greene","year":"2020","journal-title":"Clin Cancer Res"},{"issue":"8","key":"2025010619021302400_qiae064-B46","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1038\/s41419-019-1790-z","article-title":"Raptinal bypasses bax, bak, and bok for mitochondrial outer membrane permeabilization and intrinsic apoptosis","volume":"10","author":"Heimer","year":"2019","journal-title":"Cell Death Dis"},{"issue":"1","key":"2025010619021302400_qiae064-B47","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/s12935-022-02469-2","article-title":"A novel prognostic model based on single-cell RNA sequencing data for hepatocellular carcinoma","volume":"22","author":"Lu","year":"2022","journal-title":"Cancer Cell Int"},{"issue":"12","key":"2025010619021302400_qiae064-B48","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":"2020","journal-title":"Nat Rev Clin Oncol"}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jleukbio\/advance-article-pdf\/doi\/10.1093\/jleuko\/qiae064\/57273802\/qiae064.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/117\/1\/qiae064\/57273802\/qiae064.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/117\/1\/qiae064\/57273802\/qiae064.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T19:02:22Z","timestamp":1736190142000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/doi\/10.1093\/jleuko\/qiae064\/7628172"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,13]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,12,31]]}},"URL":"https:\/\/doi.org\/10.1093\/jleuko\/qiae064","relation":{},"ISSN":["1938-3673"],"issn-type":[{"type":"electronic","value":"1938-3673"}],"subject":[],"published-other":{"date-parts":[[2025,1]]},"published":{"date-parts":[[2024,3,13]]},"article-number":"qiae064"}}