論文 - 詳細
| RRC ID | 87519 |
|---|---|
| 著者 | Gallo A, Ronzio M, Campbell MB, Polettini S, Garattini E, Mantovani R, Dolfini D. |
| タイトル | A gene-expression signature defines a subtype of Stomach Adenocarcinomas with low levels of Claudins and a high ratio of NF-YA long/NF-YA short splicing variants. |
| ジャーナル | Gastric Cancer |
| Abstract |
BACKGROUND:Claudin-3, Claudin-4, and Claudin-7 are expressed on the surface of epithelial cells. Their absence in neoplastic cells of epithelial origin is an aggressiveness marker in different cancers. The NF-YA gene codes for the Nuclear-Transcription-Factor-Y-Subunit-A, which is overexpressed in various tumors. In tumors, the relative ratio of the two major NF-YA alternative splicing isoforms, NF-YA long and NF-YA short, is associated with a mesenchymal phenotype and a poor prognosis. Based on a high NF-YA long/NF-YA short ratio, we generated a 158-gene signature that is common to Claudinlow Breast Carcinomas (BRCA) and Stomach Adenocarcinomas (STAD). METHODS:To better classify STAD Claudinlow tumors, we employed a hierarchical clustering approach based on our 158-gene signature to classify STAD into a Claudinlow subgroup. We tested the classification potential of our signature in TCGA as well as in two additional datasets of tumors. We used the deep-learning DeepCC tool and the 158-gene signature to classify the STAD cell lines available in the CCLE platform. Obtained data were validated with qRT-PCR and Western blots. RESULTS:The 158-gene signature resulted in the selection of a STAD subgroup with effective Claudinlow expression and with a high NF-YA long/NF-YA short ratio. This Claudinlow subgroup was separated from the EMT subgroup of STAD and it is characterized by poor clinical outcome. We identified nine Claudinlow STAD cell lines with a high NF-YA long/NF-Y short ratio and validated the expression of selected markers. CONCLUSIONS:Our work supports the notion that three overlapping features-low expression of Claudin-3/4/7, high NF-YA long/NF-YA short ratio and a 158-gene signature-mark a specific subset of STAD characterized by mesenchymal features and poor prognosis. |
| 巻・号 | 29(1) |
| ページ | 132-146 |
| 公開日 | 2026-1-1 |
| DOI | 10.1007/s10120-025-01671-1 |
| PII | 10.1007/s10120-025-01671-1 |
| PMID | 41082105 |
| PMC | PMC12830421 |
| MeSH | Adenocarcinoma* / classification Adenocarcinoma* / genetics Adenocarcinoma* / pathology Alternative Splicing Biomarkers, Tumor* / genetics Claudins* / genetics Claudins* / metabolism Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Humans Prognosis Stomach Neoplasms* / classification Stomach Neoplasms* / genetics Stomach Neoplasms* / pathology Transcriptome |
| IF | 7.088 |
| リソース情報 | |
| ヒト・動物細胞 | LMSU(RCB1062) MKN7 MKN45(RCB1001) |