实验表明血浆代谢产物分析可以作为肺癌检测筛查方法 - 分析生活

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发表于 2018-6-28 09:45 资料个人空间短消息加为好友

实验表明血浆代谢产物分析可以作为肺癌检测筛查方法

最近，美国临床肿瘤学会(ASCO)公布的研究结果显示，通过“液体活组织检查”，分析血液中游离DNA，或可检测早期肺癌并可帮助肺癌患者选择治疗方案。早在其研究结果公布之前，就有研究者通过试验发现通过人体内的血浆代谢产物分析，可以检测和筛查肺癌检测。
近年来，可用于液体活检的生物标志物成为热门，随着基因组学、蛋白质组学、代谢组学等多种手段带来了多样化的生物标志物。美迪西可以为客户提供代谢组学技术服务。
除了传统的生物标志物，代谢组学主要研究的是作为各种代谢路径的底物和产物的小分子代谢物，其样品主要是血浆或者血清、尿液、唾液、以及细胞和组织的提取液，以及细胞和组织的提取液。主要技术手段是核磁共振仪（NMR）、液相色谱质谱联用（LC-MS）、气相色谱质谱联用（GC-MS）、色谱（HPLC、GC）等。通过检测一系列样品的谱图，再结合化学模式识别方法，可以判断出生物体的病理生理状态，基因的功能，药物的毒性和药效等，并有可能找出与之相关的潜在生物标记物。

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'%s')

研究者使用了质子核磁共振波谱对血浆进行了分析，将血浆分成了110个不同的波谱区域。这些区域分别代表不同的代谢产物。这个不同的波谱区域反应了不同代谢产物的不同浓度分布。研究者入组了233名肺癌患者以及226名非肿瘤患者作为对照组，分别检测他们的血浆代谢产物分布，从而建立代谢产物波谱模型区分肿瘤患者及对照组患者。
验证模型则入组了98名肺癌患者和89名非肿瘤患者。所有入组的肺癌患者由病理诊断为肺癌或者由经验丰富的临床医师对患者的影像学以及各项检测结果诊断为肺癌。对照组患者则为非肿瘤患者。排除标准为：1）抽血前空腹未够6小时；2）空腹血糖超过200mg/dl；3）抽血当天早晨服用其他药物；4）在5年内曾经患肿瘤疾病的患者。
实验所建立的检测模型可以准确地将78%的肺癌患者以及92%的对照组患者分组，该诊断方法的AUC为0.88。模型经过验证后发现其敏感性为71%，其特异性为81%，验证模型的AUC为0.84。结果发现肺癌患者的血浆中葡萄糖浓度增高而乳酸水平和磷脂水平则明显下降。
然而，在亚组分析中，研究发现该检测方法未能准确区分早期（Stage I）和晚期(Stage IV)的患者，然而对于Stage I和对照组的患者则可以明显区分。另外，对于不同组织学类型的肿瘤来说，该诊断方法未能准确区分鳞癌和腺癌的患者。
从这个研究我们可以发现肿瘤细胞由于其无限增殖等特殊生理功能，因此其代谢功能和相关的代谢产物是和正常细胞不同的。肿瘤细胞由于无线增值，因此所需要的能量理论上较正常细胞多。
因此可能肿瘤细胞会分解更多患者体内的糖原从而使得患者血糖有不同程度的增高。另外，由于糖原的分解功能，患者体内的无氧酵解减弱，因此乳酸水平有着不同程度的下降。
研究肿瘤的代谢是目前另一个肿瘤研究的热点，从糖代谢、脂代谢等不同代谢途径对肿瘤细胞的生理机制进行研究能为我们提供更多防治肿瘤的信息和证据。而本次研究通过检测肿瘤患者及非肿瘤患者血浆中的代谢产物从而建立了检测模型用于区分肿瘤及非肿瘤患者。
从结果而言，该研究能比较准确的区分肿瘤患者，同时该模型的特异度也是令人满意的。另外，由于只需要抽取患者的少量血液样本则可进行检测，因此相信该项检测技术在临床应用方面是比较容易被接受的。
然而，该模型还有需要改进和商榷的地方。由于该模型对患者的血浆血糖水平进行检测，因此不能对一些存在着基础代谢疾病的肿瘤患者起效。由于代谢病患者的体内代谢水平异常，可能会导致该检测结果失效。

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