{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:07:13Z","timestamp":1792109233746,"version":"4.4.0"},"reference-count":43,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T00:00:00Z","timestamp":1686700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014409","name":"Nofer Institute of Occupational Medicine","doi-asserted-by":"publisher","award":["2430\/SUB\/PNP 13.ML\/0000\/DOT_K"],"award-info":[{"award-number":["2430\/SUB\/PNP 13.ML\/0000\/DOT_K"]}],"id":[{"id":"10.13039\/501100014409","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Circadian genes are a set of genes that regulate the body\u2019s internal clock and influence various physiological processes, including sleep\u2013wake cycles, metabolism and immune function. Skin cutaneous melanoma (SKCM) is a type of skin cancer that arises from the pigment-producing cells in the skin and is the most deadly form of skin cancer. This study has investigated the relevance of circadian gene expression and immune infiltrations in the outcomes of cutaneous melanoma patients. In the present study, in silico methods based on the GEPIa, TIMER 2.0 and cBioPortal databases were performed, so as to investigate the transcript level and prognostic value of 24 circadian genes in SKCM and their relationship with the immune infiltration level. The in silico analysis showed that significantly more than half of the investigated circadian genes have an altered transcript pattern in cutaneous melanoma compared to normal skin. The mRNA levels of TIMELES and BHLHE41 were upregulated, whereas those of NFIL3, BMAL1, HLF, TEF, RORA, RORC, NR1D1, PER1, PER2, PER3, CRY2 and BHLHE40 were downregulated. The presented research shows that SKCM patients with at least one alteration of their circadian genes have decreased overall survival. Additionally, majority of the circadian genes are significantly corelated with the immune cells\u2019 infiltration level. The strongest correlation was found for neutrophils and was followed by circadian genes: NR1D2 r = 0.52 p &lt; 0.0001, BMAL1 r = 0.509 p &lt; 0.0001; CLOCK r = 0.45 p &lt; 0.0001; CSNKA1A1 r = 0.45 p &lt; 0.0001; RORA r = 0.44 p &lt; 0.0001. The infiltration level of immune cells in skin tumors has been associated with patient prognosis and treatment response. Circadian regulation of immune cell infiltration may further contribute to these prognostic and predictive markers. Examining the correlation between circadian rhythm and immune cell infiltration can provide valuable insights into disease progression and guide personalized treatment decisions.<\/jats:p>","DOI":"10.3390\/ijms241210140","type":"journal-article","created":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T01:32:57Z","timestamp":1686792777000},"page":"10140","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Disruptions of Circadian Genes in Cutaneous Melanoma\u2014An In Silico Analysis of Transcriptome Databases"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2095-8681","authenticated-orcid":false,"given":"Monika","family":"Lesicka","sequence":"first","affiliation":[{"name":"Department of Translational Research, Nofer Institute of Occupational Medicine, 91-349 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6286-0693","authenticated-orcid":false,"given":"Bogus\u0142aw","family":"Nedoszytko","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venerology and Allergology Medical University of Gdansk, 80-211 Gdansk, Poland"},{"name":"Molecular Laboratory, Invicta Fertility and Reproductive Centre, Polna 64, 81-740 Sopot, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2153-4864","authenticated-orcid":false,"given":"Edyta","family":"Reszka","sequence":"additional","affiliation":[{"name":"Department of Translational Research, Nofer Institute of Occupational Medicine, 91-349 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3322\/caac.21763","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J. 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