| RRC ID |
86129
|
| 著者 |
Horie M, Takumida H, Koba H, Ueda T, Tanaka H, Suzuki M, Ito Y, Ito A, Kondo M, Suzuki HI, Matsumoto I, Yano S, Saito A, Maeda D.
|
| タイトル |
Characteristic miRNA profiles represent clinicopathological diversity of small cell lung cancer.
|
| ジャーナル |
J Pathol
|
| Abstract |
Small cell lung cancer (SCLC) is classified into distinct molecular subtypes based on the expression patterns of four transcription regulators: achaete-scute homolog 1 (ASCL1), neuronal differentiation 1 (NEUROD1), POU class 2 homeobox 3 (POU2F3), and yes-associated protein 1 (YAP1). MicroRNAs (miRNAs) play critical roles in cancer cellular processes but their subtype-specific implications in SCLC remain underexplored. Out of 46 surgically resected SCLC samples, miRNA visualization through in situ hybridization identified high expression of miR-375 in the ASCL1, NEUROD1, and ASCL1/NEUROD1 subtypes, and miR-9-5p in the POU2F3 subtype. Comprehensive enhancer profiling using SCLC cell lines indicated that miR-375 and miR-9-5p were regulated by super-enhancers in a subtype-specific manner. Multiplex immunohistochemistry by imaging mass cytometry found that the miR-9-5p-high SCLC was characterized by a higher stromal area ratio, increased numbers of CD8+ T cells and CD163- macrophages in the intra-tumoral area, and an increased number of plasma cells in the stromal area, as compared with the miR-9-5p-low SCLC. Finally, clinicopathological analysis revealed that the miR-375-high SCLC was associated with YAP1 downregulation, increased serum pro-gastrin-releasing peptide levels, and poor prognosis. These findings highlight the critical role of super-enhancer-related miRNAs in the diversity of SCLC, and underscore the potential for novel diagnostic and prognostic biomarkers based on these subtype-specific miRNAs. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
|
| 巻・号 |
267(2)
|
| ページ |
168-180
|
| 公開日 |
2025-10-1
|
| DOI |
10.1002/path.6458
|
| PMID |
40842416
|
| PMC |
PMC12438024
|
| MeSH |
Aged
Basic Helix-Loop-Helix Transcription Factors
Biomarkers, Tumor* / genetics
Biomarkers, Tumor* / metabolism
Cell Line, Tumor
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms* / genetics
Lung Neoplasms* / pathology
Male
MicroRNAs* / genetics
MicroRNAs* / metabolism
Middle Aged
Small Cell Lung Carcinoma* / genetics
Small Cell Lung Carcinoma* / pathology
YAP-Signaling Proteins
|
| IF |
6.021
|
| リソース情報 |
| ヒト・動物細胞 |
Lu-134-A(RCB0466) |
