{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T21:49:42Z","timestamp":1785793782596,"version":"3.56.0"},"reference-count":26,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["K23K195250"],"award-info":[{"award-number":["K23K195250"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["K23K152600"],"award-info":[{"award-number":["K23K152600"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Cutaneous squamous cell carcinoma (cSCC) is a common cutaneous malignancy with diverse etiologies, including actinic keratosis, burns, and hidradenitis suppurativa (HS). Methods: We reviewed 237 cases diagnosed as cSCC in our department between 2013 and 2023. In addition, we focused on HS as an aggravating factor for cSCC. The mechanism of cSCC progression was investigated with a focus on LL-37, a peptide implicated in the pathogenesis of HS. Relevant gene expression was analyzed comprehensively via RNA sequencing in vitro. Results: The median age of the patients was 82 years (range: 33\u2013101), with 139 males and 98 females. The primary sites were as follows: head and neck (125 cases), trunk (10 cases), vulva (11 cases), extremities (81 cases), and buttocks (10 cases). Among the five cases (2.1%) of buttocks cSSc associated with HS, all cases (100%) had local recurrence or lymph node metastasis at the time of diagnosis, and one case (20%) developed multi-organ metastasis. The incidence of disease progression in cSCC originating from HS-affected buttocks was significantly higher than in other sites (p &lt; 0.05). RNA sequencing revealed the significant amplification of ACTA1, which was confirmed by Western blotting and immunohistochemical staining. Conclusions: These results suggest that HS is a prognostic factor in cSCC and that LL-37 stimulation contributes to tumor progression, partly by enhancing multiple tumor growth factors.<\/jats:p>","DOI":"10.3390\/jcm14041243","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T10:36:58Z","timestamp":1739443018000},"page":"1243","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["An Evaluation of Prognostic Factors in Cutaneous Squamous Cell Carcinoma: A Single-Center Study of 237 Japanese Cases"],"prefix":"10.3390","volume":"14","author":[{"given":"Emi","family":"Yamazaki","sequence":"first","affiliation":[{"name":"Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Fujimura","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manami","family":"Takahashi-Watanabe","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3337-5657","authenticated-orcid":false,"given":"Ryo","family":"Amagai","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Tamabuchi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6412-9570","authenticated-orcid":false,"given":"Kenta","family":"Oka","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Kambayashi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoko","family":"Omori","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehiro","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5560-9778","authenticated-orcid":false,"given":"Yoshihide","family":"Asano","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/s41568-023-00583-5","article-title":"Advances in cutaneous squamous cell carcinoma","volume":"23","author":"Winge","year":"2023","journal-title":"Nat. Rev. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Li Pomi, F., Macca, L., Motolese, A., Ingrasciotta, Y., Berretta, M., and Guarneri, C. (2021). Neoplastic Implications in Patients Suffering from Hidradenitis Suppurativa under Systemic Treatments. Biomedicines, 9.","DOI":"10.3390\/biomedicines9111594"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ramesh, U., Chiang, E., Stafford, H., Buell, J., Materia, F., Amit, M., and Yaniv, D. (2024). Cutaneous Squamous Cell Carcinoma of the Head and Neck: Pathological Features and What They Mean for Prognosis and Treatment. Cancers, 16.","DOI":"10.3390\/cancers16162866"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e000775","DOI":"10.1136\/jitc-2020-000775","article-title":"Phase 2 study of cemiplimab in patients with metastatic cutaneous squamous cell carcinoma: Primary analysis of fixed-dosing, long-term outcome of weight-based dosing","volume":"8","author":"Rischin","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Racanelli, E., Jfri, A., Gefri, A., O\u2019brien, E., Litvinov, I.V., Zubarev, A., Savin, E., and Netchiporouk, E. (2021). Cutaneous Squamous Cell Carcinoma in Patients with Hidradenitis Suppurativa. Cancers, 13.","DOI":"10.3390\/cancers13051153"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2504","DOI":"10.1016\/S0140-6736(24)00101-6","article-title":"Efficacy and safety of bimekizumab in patients with moderate-to-severe hidradenitis suppurativa (BE HEARD I and BE HEARD II): Two 48-week, randomised, double-blind, placebo-controlled, multicentre phase 3 trials","volume":"403","author":"Kimball","year":"2024","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Calabrese, L., Malvaso, D., Coscarella, G., Antonelli, F., D\u2019amore, A., Gori, N., Rubegni, P., Peris, K., and Chiricozzi, A. (2024). Therapeutic Potential of IL-1 Antagonism in Hidradenitis Suppurativa. Biomolecules, 14.","DOI":"10.3390\/biom14020175"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1111\/exd.13482","article-title":"Elevated levels of the antimicrobial peptide LL-37 in hidradenitis suppurativa are associated with a Th1\/Th17 immune response","volume":"27","author":"Thomi","year":"2018","journal-title":"Exp. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1111\/j.1365-2133.2011.10765.x","article-title":"Immunohistological pointers to a possible role for excessive cathelicidin (LL-37) expression by apocrine sweat glands in the pathogenesis of hidradenitis suppurativa\/acne inversa","volume":"166","author":"Emelianov","year":"2012","journal-title":"Br. J. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Ul Ain, Q., Schulz, C., and Pircher, J. (2023). Role of antimicrobial peptide cathelicidin in thrombosis and thromboinflammation. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1151926"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.cellimm.2012.11.009","article-title":"A comprehensive summary of LL-37, the factotum human cathelicidin peptide","volume":"280","author":"Vandamme","year":"2012","journal-title":"Cell Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Zeth, K., and Sancho-Vaello, E. (2017). The Human Antimicrobial Peptides Dermcidin and LL-37 Show Novel Distinct Pathways in Membrane Interactions. Front. Chem., 5.","DOI":"10.3389\/fchem.2017.00086"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ohuchi, K., Ikawa, T., Amagai, R., Takahashi, T., Roh, Y., Endo, J., Kambayashi, Y., Asano, Y., and Fujimura, T. (2023). LL-37 might promote local invasion of melanoma by activating melanoma cells and tumor-associated macrophages. Cancers, 15.","DOI":"10.3390\/cancers15061678"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1111\/exd.13997","article-title":"A novel technique to diagnose non-melanoma skin cancer by thermal conductivity measurements: Correlations with cancer stromal factors","volume":"28","author":"Fujimura","year":"2019","journal-title":"Exp. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"499","DOI":"10.3892\/etm.2017.4546","article-title":"Antimicrobial peptide LL-37 promotes the viability and invasion of skin squamous cell carcinoma by upregulating YB-1","volume":"14","author":"Wang","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.cell.2020.05.039","article-title":"Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma","volume":"182","author":"Ji","year":"2020","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"E448","DOI":"10.25270\/wnds\/23118","article-title":"Squamous cell carcinoma in the setting of hidradenitis suppurativa: A retrospective review of the literature","volume":"35","author":"Dixon","year":"2023","journal-title":"Wounds"},{"key":"ref_18","first-page":"e807","article-title":"Risk of squamous cell carcinoma in patients with hidradenitis suppurativa treated with anti-TNF-alpha-Results from a 12-year multicentric observational prospective study","volume":"38","author":"Marques","year":"2024","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.jaad.2021.07.035","article-title":"The inflammatory proteome of hidradenitis suppurativa skin is more expansive than that of psoriasis vulgaris","volume":"86","author":"Navrazhina","year":"2022","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1084\/jem.20150204","article-title":"A novel IL-17 signaling pathway controlling keratinocyte proliferation and tumorigenesis via the TRAF4-ERK5 axis","volume":"212","author":"Wu","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Sato, Y., Fujimura, T., Hidaka, T., Lyu, C., Tanita, K., Matsushita, S., Yamamoto, M., and Aiba, S. (2020). Possible roles of proinflammatory signaling in keratinocytes through aryl hydrocarbon receptor ligands for the development of squamous cell carcinoma. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.534323"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1093\/bjd\/ljad184","article-title":"Targeting the NLRP3 inflammasome reduces inflammation in hidradenitis suppurativa skin","volume":"189","author":"Moran","year":"2023","journal-title":"Br. J. Dermatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.3892\/ol.2016.4865","article-title":"Antimicrobial peptide LL-37 promotes the proliferation and invasion of skin squamous cell carcinoma by upregulating DNA-binding protein A","volume":"12","author":"Wang","year":"2016","journal-title":"Oncol. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1007\/s10147-019-01435-9","article-title":"Identification of SERPINE1, PLAU and ACTA1 as biomarkers of head and neck squamous cell carcinoma based on integrated bioinformatics analysis","volume":"24","author":"Yang","year":"2019","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1111\/j.1365-2133.2010.09957.x","article-title":"The antimicrobial peptide human cationic antimicrobial protein-18\/cathelicidin LL-37 as a putative growth factor for malignant melanoma","volume":"163","author":"Kim","year":"2010","journal-title":"Br. J. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Chen, S., Zhao, T., Song, Y., Huang, X., Ni, Y., Ding, L., Fu, Y., Hu, Q., and Wang, Y. (2024). Integrating clinical and genomic landscape analysis of perineural invasion identify ACTA1 as an oncogene for oral squamous cell carcinoma. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1458879"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/4\/1243\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:33:48Z","timestamp":1760027628000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/4\/1243"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,13]]},"references-count":26,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["jcm14041243"],"URL":"https:\/\/doi.org\/10.3390\/jcm14041243","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,13]]}}}