論文 - 詳細
| RRC ID | 50462 |
|---|---|
| 著者 | Hiyama N, Ando T, Maemura K, Sakatani T, Amano Y, Watanabe K, Kage H, Yatomi Y, Nagase T, Nakajima J, Takai D. |
| タイトル | Glutamate-cysteine ligase catalytic subunit is associated with cisplatin resistance in lung adenocarcinoma. |
| ジャーナル | Jpn J Clin Oncol |
| Abstract |
Background:Cisplatin is a key drug for treating lung adenocarcinoma, and its sensitivity to cisplatin is directly related to prognosis. We aimed to reveal the roles of genes related to glutathione synthesis (glutamate-cysteine ligase catalytic subunit, GCLC) and cystine uptake (cystine/glutamate transporter, xCT and CD44v8-10) in cisplatin resistance and prognosis in lung adenocarcinoma. Methods:We established cell lines stably expressing GCLC, xCT, standard isoform of CD44, and CD44v8-10, and investigated their sensitivities to cisplatin. We also measured mRNA expression levels of these genes in the tumor tissues from 92 lung adenocarcinoma patients. Patients were divided into high-expression (upper quartile, N = 23) and low-expression groups (remaining patients, N = 69). Recurrence-free survival, overall survival (N = 92), and post-recurrence survival (N = 22) were selected as endpoints. Results:Compared with the control green fluorescent protein-expressing cell line (inhibitory concentration 50:6.9 μM), all the stable cell lines were more resistant to cisplatin (12.9 μM, P = 0.025; 13.9 μM, P = 0.028; 26.7 μM, P = 0.001; 17.7 μM, P = 0.008, respectively). In contrast, there was no significant difference in recurrence-free or overall survival between the high- and low-expression groups for any of the genes. However, high expression of GCLC was a risk factor for poorer post-recurrence survival (hazard ratio, 6.26; 95% confidence interval, 1.37-28.7; P = 0.018). Conclusion:High expression levels of genes related to glutathione synthesis and cystine uptake promote cisplatin resistance in lung adenocarcinoma cell lines. High expression of GCLC in tumor tissue may be a potential predictor of treatment failure. |
| 巻・号 | 48(4) |
| ページ | 303-307 |
| 公開日 | 2018-4-1 |
| DOI | 10.1093/jjco/hyy013 |
| PII | 4883196 |
| PMID | 29474642 |
| PMC | PMC5892860 |
| MeSH | Adenocarcinoma / drug therapy* Adenocarcinoma / enzymology* Adenocarcinoma / genetics Adenocarcinoma / pathology Adenocarcinoma of Lung Aged Catalytic Domain* Cell Line, Tumor Cisplatin / pharmacology Cisplatin / therapeutic use* Drug Resistance, Neoplasm* / drug effects Female Gene Expression Regulation, Neoplastic / drug effects Glutamate-Cysteine Ligase / genetics Glutamate-Cysteine Ligase / metabolism* Humans Inhibitory Concentration 50 Lung Neoplasms / drug therapy* Lung Neoplasms / enzymology* Lung Neoplasms / genetics Lung Neoplasms / pathology RNA, Messenger / genetics RNA, Messenger / metabolism Survival Analysis |
| IF | 2.183 |
| 引用数 | 7 |
| リソース情報 | |
| 遺伝子材料 | CSII-CMV-MCS-IRES2-Bsd (RDB04385) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394). |