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MicroRNAs (miRNAs) play critical roles in cancer cellular processes but their subtype\u2010specific implications in SCLC remain underexplored. Out of 46 surgically resected SCLC samples, miRNA visualization through <jats:italic>in situ<\/jats:italic> hybridization identified high expression of miR\u2010375 in the ASCL1, NEUROD1, and ASCL1\/NEUROD1 subtypes, and miR\u20109\u20105p in the POU2F3 subtype. Comprehensive enhancer profiling using SCLC cell lines indicated that miR\u2010375 and miR\u20109\u20105p were regulated by super\u2010enhancers in a subtype\u2010specific manner. Multiplex immunohistochemistry by imaging mass cytometry found that the miR\u20109\u20105p\u2010high SCLC was characterized by a higher stromal area ratio, increased numbers of CD8<jats:sup>+<\/jats:sup> T cells and CD163<jats:sup>\u2212<\/jats:sup> macrophages in the intra\u2010tumoral area, and an increased number of plasma cells in the stromal area, as compared with the miR\u20109\u20105p\u2010low SCLC. Finally, clinicopathological analysis revealed that the miR\u2010375\u2010high SCLC was associated with YAP1 downregulation, increased serum pro\u2010gastrin\u2010releasing peptide levels, and poor prognosis. These findings highlight the critical role of super\u2010enhancer\u2010related miRNAs in the diversity of SCLC, and underscore the potential for novel diagnostic and prognostic biomarkers based on these subtype\u2010specific miRNAs. \u00a9 2025 The Author(s). <jats:italic>The Journal of Pathology<\/jats:italic> published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.6458","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T08:09:52Z","timestamp":1755850192000},"page":"168-180","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Characteristic <scp>miRNA<\/scp> profiles represent clinicopathological diversity of small cell lung cancer"],"prefix":"10.1002","volume":"267","author":[{"given":"Masafumi","family":"Horie","sequence":"first","affiliation":[{"name":"Division of Molecular and Genomic Pathology, 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