論文 - 詳細
| RRC ID | 58777 |
|---|---|
| 著者 | Nishibeppu K, Komatsu S, Imamura T, Kiuchi J, Kishimoto T, Arita T, Kosuga T, Konishi H, Kubota T, Shiozaki A, Fujiwara H, Okamoto K, Otsuji E. |
| タイトル | Plasma microRNA profiles: identification of miR-1229-3p as a novel chemoresistant and prognostic biomarker in gastric cancer. |
| ジャーナル | Sci Rep |
| Abstract |
This study aimed to explore novel microRNAs in plasma for predicting chemoresistance in adjuvant chemotherapy for patients with gastric cancer (GC). We used the Toray 3D-Gene microRNA array-based approach to compare preoperative plasma microRNA levels between GC patients with and without recurrences after curative gastrectomy. All patients underwent adjuvant chemotherapy with S-1, an oral fluoropyrimidine. Of 2566 candidates, six candidate microRNAs (miR-1229-3p, 1249-5p, 762, 711, 1268a and 1260b), which were highly expressed in the preoperative plasma of patients with subsequent recurrences, were selected. In a large-scale validation analysis by quantitative RT-PCR, we focused on high plasma levels of miR-1229-3p, which was an independent poor prognostic factor for recurrence free survival (P = 0.009, HR = 3.71). Overexpression of miR-1229-3p in GC cells induced significant chemoresistance to 5-fluorouracil (5-FU), up-regulation of thymidylate synthase (TS) and dihydroprimidine dehydrogenase (DPD) and down-regulation of SLC22A7 both in vitro and in vivo. Intraperitoneal injection of miR-1229-3p in mice induced significant chemoresistance to 5-FU, accompanied by high levels of miR-1229-3p in plasma and tumor tissue. These findings suggest that plasma miR-1229-3p might be a clinically useful biomarker for predicting chemoresistance to S-1 and selecting other or combined intensive chemotherapy regimens in GC patients. |
| 巻・号 | 10(1) |
| ページ | 3161 |
| 公開日 | 2020-2-21 |
| DOI | 10.1038/s41598-020-59939-8 |
| PII | 10.1038/s41598-020-59939-8 |
| PMID | 32081926 |
| PMC | PMC7035283 |
| MeSH | Animals Biomarkers, Tumor / blood* Cell Line, Tumor Cell Movement Cell Survival Disease-Free Survival Drug Combinations Drug Resistance, Neoplasm* Female Fluorouracil Gastrectomy Humans Male Mice Mice, Inbred BALB C Mice, Nude MicroRNAs / blood* Neoplasm Invasiveness Neoplasm Recurrence, Local Organic Anion Transporters, Sodium-Independent / genetics Oxonic Acid / therapeutic use* Prognosis Proportional Hazards Models Stomach Neoplasms / blood* Tegafur / therapeutic use* |
| IF | 3.998 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HGC-27(RCB0500) |