青少年特发性脊柱侧凸患者循环游离核 DNA 和线粒体 DNA 的变化。
Changes in circulating cell-free nuclear DNA and mitochondrial DNA of patients with adolescent idiopathic scoliosis.
机构信息
Department of Spine Surgery, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha, 410008, China.
出版信息
BMC Musculoskelet Disord. 2019 Oct 25;20(1):479. doi: 10.1186/s12891-019-2869-5.
BACKGROUND
Adolescent idiopathic scoliosis (AIS) which characterized by complex three-dimensional deformity of spine has been difficult to cure because of the unknown etiopathology and uncertainty of progression. Nowadays, circulating cell-free (ccf) DNA was found to be a potential biomarker for several benign and malignant diseases. However, whether ccf DNA can be a biomarker for AIS has not been reported yet. In this study, we investigate the circulating cell-free nuclear DNA (ccf n-DNA) and mitochondrial DNA (ccf mt-DNA) concentrations in the plasma of patients with AIS and controls (CT), and the changed plasma ccf n-DNA and ccf mt-DNA levels and their association with clinical parameters were assessed.
METHODS
The plasma of peripheral blood from 69 AIS patients and 21 age-matched CT was collected for ccf DNA analysis. Quantitative PCR was used to detect ccf n-DNA and ccf mt-DNA levels, and correlation analyses between the ccf n-DNA and ccf mt-DNA levels and clinical characteristics were conducted. Receiver operator curves (ROC) were used to analyze the sensitivity and specificity of ccf n-DNA and ccf mt-DNA levels to different characteristics.
RESULTS
The plasma ccf n-DNA levels of both GAPDH and ACTB were significantly decreased in AIS patients compared with those in controls, while the plasma ccf mt-DNA levels did not changed. According to sex-related analyses, the ccf n-DNA levels in male CT-M was higher than that in female CT and male AIS, but the ccf n-DNA levels in female AIS was not significantly changed when compared with male AIS or female CT. However, the concentration of ccf mt-DNA in female AIS increased significantly when compared with male AIS. Surprisingly, Lenke type-related analyses suggested that Lenke type 1 patients had lower ccf n-DNA levels, whereas Lenke type 5 patients had higher ccf mt-DNA levels compared with those of controls. However, a lower sensitivity and specificity of AIS predicted by ccf n-DNA or ccf mt-DNA levels was observed, whether in total, by sex, or by Lenke type.
CONCLUSION
Although with no/little predictive accuracy of AIS/progressed AIS by ccf DNA levels, significantly changed plasma ccf DNA levels were observed in AIS patients compared with those in controls.
背景
青少年特发性脊柱侧凸（AIS）以脊柱复杂的三维畸形为特征，由于病因不明和进展的不确定性，难以治愈。如今，循环无细胞（ccf）DNA 被发现是几种良性和恶性疾病的潜在生物标志物。然而，ccf DNA 是否可以作为 AIS 的生物标志物尚未报道。在这项研究中，我们研究了 AIS 患者和对照组（CT）血浆中的循环无细胞核 DNA（ccf n-DNA）和线粒体 DNA（ccf mt-DNA）浓度，并评估了血浆 ccf n-DNA 和 ccf mt-DNA 水平的变化及其与临床参数的关系。
方法
收集 69 例 AIS 患者和 21 例年龄匹配的 CT 的外周血血浆，进行 ccf DNA 分析。定量 PCR 用于检测 ccf n-DNA 和 ccf mt-DNA 水平，并对 ccf n-DNA 和 ccf mt-DNA 水平与临床特征之间的相关性进行分析。接收者操作特征曲线（ROC）用于分析 ccf n-DNA 和 ccf mt-DNA 水平对不同特征的敏感性和特异性。
结果
与 CT 相比，AIS 患者的 GAPDH 和 ACTB 血浆 ccf n-DNA 水平均显著降低，而 ccf mt-DNA 水平无变化。根据性别相关分析，男性 CT-M 的 ccf n-DNA 水平高于女性 CT 和男性 AIS，但女性 AIS 的 ccf n-DNA 水平与男性 AIS 或女性 CT 相比无明显变化。然而，女性 AIS 中 ccf mt-DNA 的浓度显著升高。令人惊讶的是，Lenke 型相关分析表明，与对照组相比，Lenke 1 型患者的 ccf n-DNA 水平较低，而 Lenke 5 型患者的 ccf mt-DNA 水平较高。然而，无论总人群、按性别还是按 Lenke 型，ccf n-DNA 或 ccf mt-DNA 水平预测 AIS/进展性 AIS 的敏感性和特异性均较低。
结论
尽管 ccf DNA 水平对 AIS/进展性 AIS 的预测准确性较低，但与对照组相比，AIS 患者的血浆 ccf DNA 水平明显发生变化。
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