关键词: 上皮性卵巢癌')">

上皮性卵巢癌, 化疗耐药, 不良预后, hsa_circ_0004390

Abstract:

【Abstract】Objective To investigate the relationship between serum exosome hsa_circ_0004390 and chemotherapy resistance and adverse prognosis in patients with epithelial ovarian cancer (EOC). Methods From January to December 2017, the cancer tissue and serum samples of 87 patients with primary EOC were collected from the First Department of Oncology of Qidong People’s Hospital (QidongHospital affiliated to Nantong University), and 85 healthy female volunteers were recruited to obtain control serum samples. The patients who were ineffective in adjuvant chemotherapy or had disease progression within 6 months were included in the drug resistance group (n=30), and the other patients were included in the sensitive group (n=57). Tissue samples from 10 patients undergoing radical surgery were used for next generation sequencing (NGS) to screen the circRNA gene spectrum. The expression level of candidate circRNAs gene was verified by real-time fluorescent quantitative PCR (qPCR).Results Among the circRNA genes identified by NGS, a total of 285 circrnas expressed differently in the EOC tissues of the drug-resistant group and the sensitive group (P＜0.05). After verification, the relative expression levels of hsa_circ_0004390 (P＝0.004) and hsa_circ_0006276 (P＝0.045) in the EOC tissue of the 5 patients in the drug-resistant group were higher than sensitive group, so we chose these two genes for further analysis. q-PCR showed that compared with the control group, the relative expression of serum exosomalhsa_circ_0004390 [2.57 (1.47, 2.99) vs. 0.94 (0.61, 1.35), P＜0.001] and hsa_circ_0006276 [1.26 (1.03, 1.46) vs. 0.87 (0.67, 1.39), P＝0.001] in EOC group were significantly increased. Further analysis of the working characteristic curve of the subjects found that the serum exosomalhsa_circ_0004390 was more effective in the diagnosis of EOC. In addition, the expression of serum exosomalhsa_circ_0004390 in patients with drug resistance was significantly higher than that in patients with sensitivity group [3.07 (2.66, 3.66) vs. 1.69 (1.23, 2.59), P＜0.001]. However, serum exosomalhsa_circ_0006276 was not associated with platinum chemotherapy reaction (P＞0.05). After further adjusting the Objective  interference factors, it was found that the serum exosomalhsa_circ_0004390 was an independent risk factor affecting the platinum chemotherapy response in EOC patients (P＜0.05). In addition, patients with low level of serum exosomalhsa_circ_0004390 expression (＜2.57) and patients with high level (≥2.57) of OS were better (P＝0.005).Conclusion Serum exosome hsa_circ_0004390 contribute to predict the chemotherapeutic response and survival prognosis of Platinum-based EOC patients, which may provide a new target for EOC treatment.

Key words: Epithelial ovarian cancer')">

Epithelial ovarian cancer, Chemotherapy resistance, Adverse prognosis, hsa_circ_0004390