論文 - 詳細
| RRC ID | 72037 |
|---|---|
| 著者 | Tanaka M, Kunita A, Yamagishi M, Katoh H, Ishikawa S, Yamamoto H, Abe J, Arita J, Hasegawa K, Shibata T, Ushiku T. |
| タイトル | KRAS mutation in intrahepatic cholangiocarcinoma: Linkage with metastasis-free survival and reduced E-cadherin expression. |
| ジャーナル | Liver Int |
| Abstract |
BACKGROUND & AIMS:Although KRAS mutations are the major driver of intrahepatic cholangiocarcinoma (ICC), their role remains unexplored. This study aimed to elucidate the prognostic effects, association with clinicopathologic characteristics and potent functions of KRAS mutations in ICC. METHODS:107 resected stage I-III ICCs were analyzed for KRAS mutation status and its link with clinicopathological features. An independent validation cohort (n = 138) was included. In vitro analyses using KRAS-mutant ICC cell lines were performed. RESULTS:KRAS mutation was significantly associated with worse overall survival in stage I-III ICCs, which was validated in an independent cohort. Recurrence-free survival did not significantly differ between cases with and without KRAS mutations, but if limited to recurrence with extrahepatic metastasis, KRAS-mutant cases showed significantly worse distant metastasis-free survival than KRAS-wild cases showed. KRAS mutations were associated with frequent tumor budding with reduced E-cadherin expression. In vitro, KRAS depletion caused marked inhibition of cell growth and migration together with E-cadherin upregulation in KRAS-mutant ICC cells. RNA sequencing assay revealed that KRAS depletion caused MYC pathway downregulation and interferon pathway upregulation. CONCLUSIONS:Our observations suggest that KRAS mutations are associated with aggressive behavior of ICC, especially the development of extrahepatic metastasis. Mutant KRAS is likely to change the adhesive status of ICC cells, affect the responsiveness of tumor cells to interferon immune signals, and consequently promote extrahepatic metastasis. KRAS mutation status, which predicts the prognoses of patients with ICC after surgical resection, is expected to help stratify patients better for individual postoperative treatment strategies. |
| 巻・号 | 42(10) |
| ページ | 2329-2340 |
| 公開日 | 2022-10-1 |
| DOI | 10.1111/liv.15366 |
| PMID | 35833881 |
| MeSH | Antigens, CD Bile Duct Neoplasms* / genetics Bile Duct Neoplasms* / metabolism Bile Duct Neoplasms* / surgery Bile Ducts, Intrahepatic / pathology Cadherins* / genetics Cholangiocarcinoma* / genetics Cholangiocarcinoma* / metabolism Cholangiocarcinoma* / surgery Disease-Free Survival Humans Interferons Mutation Prognosis Proto-Oncogene Proteins p21(ras)* / genetics |
| IF | 5.175 |
| リソース情報 | |
| ヒト・動物細胞 | HuCCT1(RCB1960) RBE(RCB1292) |