論文 - 詳細
| RRC ID | 51706 |
|---|---|
| 著者 | Nakahara Y, Yamasaki M, Sawada G, Miyazaki Y, Makino T, Takahashi T, Kurokawa Y, Nakajima K, Takiguchi S, Mimori K, Mori M, Doki Y. |
| タイトル | Downregulation of SIRT4 Expression Is Associated with Poor Prognosis in Esophageal Squamous Cell Carcinoma. |
| ジャーナル | Oncology |
| Abstract |
OBJECTIVE:SIRT4, a mitochondria-localized sirtuin, represses glutamine metabolism by inhibiting glutamate dehydrogenase (GDH). The current study aimed to evaluate the clinical and biological significance of SIRT4 in esophageal squamous cell carcinoma (ESCC). METHODS:The study comprised 172 patients with surgically resected ESCC in two independent cohorts. SIRT4 mRNA expression was analyzed in Cohort 1 (n = 79) and SIRT4 protein expression in Cohort 2 (n = 93). The association of SIRT4 expression with clinicopathological parameters and prognosis was assessed. Furthermore, the biological role of SIRT4 in ESCC cell lines was examined. RESULTS:SIRT4 expression was not correlated with any clinicopathological parameters in both cohorts. In Cohort 1, low-SIRT4-expression cases had poorer overall survival than high-SIRT4-expression cases (p = 0.016). In Cohort 2, SIRT4-negative cases had poorer overall survival and disease-free survival than SIRT4-positive cases (p = 0.011 and 0.0026). Multivariate analysis revealed that SIRT4 expression was an independent prognostic factor for overall survival (HR = 2.06, p = 0.038). The rate of distant recurrence was significantly higher in SIRT4-negative cases than in SIRT4-positive cases (39.4 vs. 7.4%; p = 0.0023). In vitro, SIRT4 knockdown significantly increased GDH activity and promoted cell proliferation and migration. CONCLUSION:SIRT4 is a potential prognostic biomarker in ESCC. |
| 巻・号 | 90(6) |
| ページ | 347-55 |
| 公開日 | 2016-1-1 |
| DOI | 10.1159/000445323 |
| PII | 000445323 |
| PMID | 27082627 |
| MeSH | Adult Aged Biomarkers, Tumor / genetics Biomarkers, Tumor / metabolism* Carcinoma, Squamous Cell / metabolism* Carcinoma, Squamous Cell / pathology* Cell Line, Tumor Cell Movement Cell Proliferation Disease-Free Survival Down-Regulation Esophageal Neoplasms / metabolism* Esophageal Neoplasms / pathology* Esophageal Squamous Cell Carcinoma Female Gene Expression Regulation, Neoplastic Humans Immunohistochemistry Kaplan-Meier Estimate Lymphatic Metastasis Male Middle Aged Mitochondrial Proteins / genetics Mitochondrial Proteins / metabolism* Neoplasm Invasiveness Neoplasm Recurrence, Local / metabolism Predictive Value of Tests Prognosis Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Sirtuins / genetics Sirtuins / metabolism* |
| IF | 2.642 |
| 引用数 | 17 |
| リソース情報 | |
| ヒト・動物細胞 | TE-4(RCB2097) TE-8(RCB2098) TE-9(RCB1988) TE-11(RCB2100) |