| 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
|
| リソース情報 |
| ヒト・動物細胞 |
HGC-27(RCB0500) |
