Ge Li, Li Ning, Liu Mei, Xu Ning-Zhi, Wang Ming-Rong, Wu Ling-Ying
Department of Gynecologic Oncology State Key Laboratory of Molecular Oncology, National Cancer Center /Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Medicine (Baltimore). 2017 Jul;96(30):e7621. doi: 10.1097/MD.0000000000007621.
Platinum resistance is a critical barrier for clinicians to improve the survival of ovarian cancer. Our study evaluated the correlation between copy number variations (CNVs) of neurotrophic tyrosine receptor kinase 3 (NTRK3) and the prognosis of ovarian cancer, which might predict platinum resistance in ovarian cancer patients.Array comparative genomic hybridization (CGH) was used to test gene backgrounds between platinum-sensitive and platinum-resistant relapsed populations and CNVs of NTRK3 were indicated by cluster analysis. Fluorescence in situ hybridization (FISH) was adopted in 41 cases for further verification, which confirmed the results of array CGH. Spearman's rank correlation analysis and χ test were used to evaluate the accuracy of CNVs of NTRK3 which predicted platinum-sensitive or platinum-resistant recurrence.We detected CNVs of NTRK3 between 2 groups by array CGH, and amplification of NTRK3 was confirmed by FISH in the platinum-sensitive recurrence group with enlarged samples. The test concordance of 2 methods was 78.6%. Among 41 cases with satisfied FISH results, the median time to recurrence (TTR) of patients with amplified and nonamplified NTRK3 were respectively 18 and 5 months (P <.01). The cut-off value of TTR to differentiate platinum-sensitive or platinum-resistant recurrence was 6 months in accordance with clinical practice. According to the above standard, 15 cases with NTRK3 amplification were platinum-sensitive and 12 cases without NTRK3 amplification were platinum-resistant recurrences which demonstrated that the accuracy of NTRK3 amplification/nonamplification to predict recurrent types was 65.9% (27/41).CNVs of NTRK3 were associated with platinum-sensitive and platinum-resistant recurrences. Amplification of NTRK3 perfectly predicted platinum-sensitive relapse of ovarian cancer.
铂耐药是临床医生提高卵巢癌患者生存率的关键障碍。我们的研究评估了神经营养性酪氨酸受体激酶3(NTRK3)的拷贝数变异(CNV)与卵巢癌预后之间的相关性,这可能预测卵巢癌患者的铂耐药情况。采用阵列比较基因组杂交(CGH)检测铂敏感和铂耐药复发人群之间的基因背景,并通过聚类分析显示NTRK3的CNV。对41例患者采用荧光原位杂交(FISH)进行进一步验证,证实了阵列CGH的结果。采用Spearman等级相关分析和χ检验评估NTRK3的CNV预测铂敏感或铂耐药复发的准确性。
我们通过阵列CGH检测两组之间NTRK3的CNV,并在铂敏感复发组中对扩大样本通过FISH证实了NTRK3的扩增。两种方法的检测一致性为78.6%。在41例FISH结果满意的患者中,NTRK3扩增和未扩增患者的中位复发时间(TTR)分别为18个月和5个月(P<0.01)。根据临床实践,区分铂敏感或铂耐药复发的TTR临界值为6个月。根据上述标准,15例NTRK3扩增患者为铂敏感复发,12例无NTRK3扩增患者为铂耐药复发,这表明NTRK3扩增/未扩增预测复发类型的准确性为65.9%(27/41)。
NTRK3的CNV与铂敏感和铂耐药复发相关。NTRK3的扩增完美地预测了卵巢癌的铂敏感复发。