Circular RNA SMARCA5 correlates with favorable clinical tumor features and prognosis, and increases chemotherapy sensitivity in intrahepatic cholangiocarcinoma
Circular RNA SMARCA5 correlates with favorable clinical tumor features and prognosis, and increases chemotherapy sensitivity in intrahepatic cholangiocarcinoma
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DOI：
10.1002/jcla.23138
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发表时间：
2019-12-27
影响因子：
2.7
通讯作者：
Fang, Tao
中科院分区：
文献类型：
--
作者：
Lu, Qi;Fang, Tao
目的探讨环状RNA SMARCA 5（circ-SMARCA 5）与肝内胆管癌（ICC）临床病理特征及总生存期（OS）的关系，以及circ-SMARCA 5对ICC细胞增殖及顺铂/吉西他滨化疗敏感性的影响。方法收集92例经手术切除的原发性ICC患者的肿瘤组织及癌旁组织，进行circ-SMARCA 5检测。将circ-SMARCA 5过表达质粒转染TFK-1和HuH-28 ICC细胞后，检测circ-SMARCA 5对细胞增殖和化疗敏感性的影响。结果与癌旁组织相比，ICC组织中Circ-SMARCA 5的表达降低。肿瘤circ-SMARCA 5高表达与东部肿瘤协作组表现评分、T分期、N分期、TNM分期和异常CA 199状态呈负相关。此外，与低表达患者相比，肿瘤circ-SMARCA 5高表达患者的OS增加，进一步的多变量考克斯回归表明，肿瘤circ-SMARCA 5高表达是OS更长的独立预测因素。在TFK-1和HuH-28 ICC细胞中，circ-SMARCA 5上调降低了细胞增殖，降低了顺铂处理和吉西他滨处理细胞的相对细胞活力，顺铂和吉西他滨的半数抑制浓度（IC 50）也降低。结论circ-SMARCA 5与ICC的临床特征、生存特征及化疗敏感性的相关性提示其可作为ICC疾病进展及预后监测的重要生物标志物。
Objective This present study aimed to investigate the correlation of circular RNA SMARCA5 (circ-SMARCA5) with clinicopathological features and overall survival (OS), and the effect of circ-SMARCA5 on cell proliferation and chemotherapy sensitivity to cisplatin/gemcitabine in intrahepatic cholangiocarcinoma (ICC). Methods Totally 92 primary ICC patients who underwent resection were recruited, and their tumor tissues and adjacent tissues were collected for circ-SMARCA5 detection. The effect of circ-SMARCA5 on cell proliferation and chemotherapy sensitivity was detected after circ-SMARCA5 overexpression plasmid transfection into TFK-1 and HuH-28 ICC cells. Results Circ-SMARCA5 expression was reduced in ICC tumor tissues compared to adjacent tissues. Tumor circ-SMARCA5 high expression was negatively associated with Eastern Cooperative Oncology Group performance score, T stage, N stage, TNM stage, and abnormal CA199 status. Furthermore, OS was increased in patients with tumor circ-SMARCA5 high expression compared with those with low expression, and further multivariate Cox's regression demonstrated that tumor circ-SMARCA5 high expression was an independent predictive factor for longer OS. In TFK-1 and HuH-28 ICC cells, circ-SMARCA5 upregulation decreased cell proliferation, reduced relative cell viability in cisplatin-treated as well as gemcitabine-treated cells, and also decreased inhibitory concentration by 50% value (IC50) of cisplatin and gemcitabine. Conclusion The correlation of circ-SMARCA5 with favorable clinical tumor features, survival profile, and its promoting effect on chemotherapy sensitivity implies its potential as a valuable biomarker in monitoring disease progression and prognosis of ICC.