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首页> 外文期刊>Journal of Thoracic Disease >Circular RNA profiling identified as a biomarker for predicting the efficacy of Gefitinib therapy for non-small cell lung cancer
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Circular RNA profiling identified as a biomarker for predicting the efficacy of Gefitinib therapy for non-small cell lung cancer

机译：环形RNA分析被鉴定为可预测吉非替尼治疗非小细胞肺癌疗效的生物标志物

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Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have become important treatment options for non-small cell lung cancer (NSCLC) patients with EGFR sensitive mutation. However, the detection of EGFR driver mutation is impeded by the lack of adequate tumor tissues, histopathological type, long detection period, and the heterogeneity of a tumor. Therefore, it is necessary to develop a more convenient method to guide the clinical use of EGFR-TKI. Circular RNAs (circRNAs) are characterized as a closed structure with covalently joined ends resistant to exonucleases may be a potential biomarker. In the present study, we aimed to screen circRNAs that may be associated with the efficacy of EGFR-TKI. Methods: The expression of circRNAs sequenced by circular microarray in plasma samples between gefitinib effective and ineffective groups were compared. RT-qPCR further validated the results in an independent cohort. Kaplan-Meier curves were used to analyze the association between circRNA and progression-free survival (PFS) of NSCLC patients treated with gefitinib. Results: In total, 52 NSCLC patients treated with gefitinib were included for analysis. 1,377 circRNAs were differentially expressed in gefitinib effective and ineffective groups, among which 989 circRNAs were up-regulated, and 388 circRNAs were down-regulated in the effective group. Furthermore, two differentially expressed circRNAs, hsa_circ_0109320 and hsa_circ_0134501, were validated by RT-qPCR in an independent cohort of 38 gefitinib-treated NSCLC patients. Elevated hsa_circ_0109320 was associated with longer PFS in gefitinib-treated NSCLC patients. Conclusions: Taken together, hsa_circ_0109320 may be a potential biomarker for the efficacy of EGFR-TKI in NSCLC patients. This provides a new molecular typing method for individualized precision treatment.
机译：背景：表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）已成为具有EGFR敏感突变的非小细胞肺癌（NSCLC）患者的重要治疗选择。然而，由于缺乏足够的肿瘤组织，组织病理学类型，较长的检测时间和肿瘤的异质性阻碍了EGFR驱动子突变的检测。因此，有必要开发一种更方便的方法来指导EGFR-TKI的临床应用。环状RNA（circRNA）的特征是具有一个对核酸外切酶具有抗性的共价连接末端的封闭结构可能是潜在的生物标记。在本研究中，我们旨在筛选可能与EGFR-TKI疗效相关的circRNA。方法：比较吉非替尼有效组和无效组血浆样品中通过环形微阵列测序的circRNA的表达。 RT-qPCR在一个独立的队列中进一步验证了结果。 Kaplan-Meier曲线用于分析吉非替尼治疗的NSCLC患者circRNA与无进展生存期（PFS）之间的关联。结果：总共包括52例接受吉非替尼治疗的NSCLC患者进行分析。在吉非替尼有效和无效组中差异表达了1,377个circRNA，其中有效组中989个circRNA上调，而388个circRNA下调。此外，在38个接受吉非替尼治疗的NSCLC患者的独立队列中，通过RT-qPCR验证了两种差异表达的circRNA，即hsa_circ_0109320和hsa_circ_0134501。在吉非替尼治疗的NSCLC患者中，hsa_circ_0109320升高与更长的PFS相关。结论：综上所述，hsa_circ_0109320可能是EGFR-TKI在NSCLC患者中疗效的潜在生物标志物。这为个体化的精密治疗提供了一种新的分子分型方法。

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