脑脊液miR-139、miR-22水平对肺腺癌脑转移瘤的诊断价值研究

目的分析脑脊液微小RNA-139(miR-139)、微小RNA-22(miR-22)水平对肺腺癌脑转移瘤的诊断价值。方法选取2017年6月至2021年12月于该院收治并确诊为肺腺癌脑转移瘤患者80例作为肺腺癌脑转移组,单纯肺腺癌无转移患者60例作为肺腺癌无转移组。采用实时荧光定量PCR检测所有患者脑脊液中miR-139、miR-22水平。分析肺腺癌脑转移瘤患者脑脊液中miR-139、miR-22水平与临床病理参数的关系及这两个微小RNA水平的相关性,影响肺腺癌患者发生脑转移瘤的危险因素,以及miR-139、miR-22对肺腺癌患者发生脑转移瘤的诊断价值。体外培养肺腺癌细胞A549,并随机分为对照(Control)组、miR-139模拟物(mimic)组、miR-22 mimic组、miR-139抑制物(inhibitor)组、miR-22 inhibitor组,检测各组miR-139、miR-22水平及细胞侵袭和迁移能力。结果与肺腺癌无转移组相比,肺腺癌脑转移组患者脑脊液中miR-139、miR-22水平显著降低(P<0.05)。肺腺癌脑转移瘤患者脑脊液中miR-139、miR-22水平与原发肿瘤数目、原发肿瘤分化程度、淋巴结转移有关(P<0.05)。肺腺癌脑转移瘤患者脑脊液中miR-139与miR-22水平呈正相关(P<0.05)。miR-139低表达、miR-22低表达是影响肺腺癌患者发生脑转移瘤的独立危险因素(P<0.05)。脑脊液中miR-139、miR-22单独及二者联合诊断肺腺癌患者发生脑转移瘤的曲线下面积分别为0.827、0.795、0.953。过表达miR-139、miR-22可显著抑制A549细胞的侵袭和迁移,而抑制miR-139、miR-22则可以观察到相反的结果(P<0.05)。结论肺腺癌脑转移瘤患者脑脊液中miR-139、miR-22均呈低水平,二者对肺腺癌脑转移瘤的诊断均具有一定价值。

基于MRI纹理特征的肺腺癌脑转移瘤诊断及对肺腺癌脑转移EGFR基因突变的预测

目的探讨基于MRI纹理特征的肺腺癌脑转移瘤诊断及对肺腺癌脑转移EGFR基因突变的预测价值。方法选取154例肺腺癌患者,根据是否脑转移将患者分成脑转移组(n=71)和非脑转移组(n=83)。比较两组患者MRI纹理特征指标,评估能量、熵、惯性矩、相关和逆差矩对肺腺癌脑转移的诊断价值。针对脑转移组患者行EGFR基因检测,将患者分成EGFR突变组(n=33)和EGFR野生组(n=38),单因素和多因素Logistic回归分析确定MRI纹理特征对肺腺癌脑转移患者EGFR基因突变的影响因素。结果脑转移组患者熵和相关等明显高于非脑转移组,脑转移组患者能量、惯性矩和逆差矩明显低于非脑转移组。根据ROC曲线可得,能量的临界值为0.00121,敏感度为69.01%,特异度为71.08%,AUC为0.801(95%CI:0.750~0.852);熵的临界值为10.42,敏感度为73.24%,特异度为69.88%,AUC为0.760(95%CI:0.707~0.812);惯性矩的临界值为7139.86,敏感度为64.79%,特异度为60.24%,曲线下面积(AUC)为0.708(95%CI:0.645~0.772);相关的临界值为0.000026,敏感度为59.15%,特异度为60.24%,AUC为0.631(95%CI:0.564~0.698);逆差矩的临界值为0.0301,敏感度为74.65%,特异度为78.31%,AUC为0.816(95%CI:0.768~0.864)。回归分析在最佳临界值是对应的敏感度为80.28%,特异性为80.72%,AUC为0.869(95%CI:0.831~0.907),回归分析的敏感度和特异性明显高于MRI纹理特征的单独诊断。Logistic分析显示,能量、熵、惯性矩、相关和逆差矩是肺腺癌脑转移EGFR基因突变的影响因素(P<0.05)。结论能量、熵、惯性矩、相关及逆差矩等MRI纹理特征在肺腺癌脑转移瘤中异常表达,单独及回归分析联合诊断可应用于提高肺癌脑转移的诊断效能;且基于MRI纹理特征分析可以用于预测肺腺癌脑转移EGFR基因突变。

人脑转移癌组织裸小鼠脑内移植模型的建立

目的建立人肺腺癌脑转移瘤的裸小鼠原位移植模型，并分析移植瘤的生物学特征。方法取人肺腺癌脑转移瘤组织块，接种于裸小鼠右尾状核。致瘤后即用裸小鼠的瘤组织进行其原位传代接种，观察致瘤率及荷瘤鼠生存期；MRI观察移植瘤在鼠脑内的大体形态；HE染色分析各代移植瘤的组织学形态；免疫组化染色观察移植瘤中CEA的表达；Alcian blue／PAS特殊染色检测移植瘤中粘液的性质。结果移植瘤组织在裸小鼠右尾状核已连续传至6代，共65只鼠。荷瘤鼠生存期：原代为（47．6±1．8）d，2～3代有所缩短，4～6代稳定在（38．0±0．9）d；移植瘤MRI类圆形，瘤周无水肿。移植瘤病理为低分化腺癌，不向周围正常鼠脑组织浸润；移植瘤中CEA表达阳性，有酸性粘液存在。结论人肺腺癌脑转移瘤组织块接种于鼠脑内建立的原位移植模型能更好地模拟临床原发肿瘤的病理学特征，本方法为研究人肺腺癌脑转移瘤的生物学特性及实验治疗提供了一个可靠的动物模型。

Comparative Study of CT Images of Cerebral Metastasis from Pulmonary Squamous Cell Carcinoma and Adenocarcinoma

Objective: To explore the di?erence of CT images of metastatic tumors to the brain of lung squamous cell cancer and lung glandular cancer. Methods: Forty-?ve cases of lung squamous cell cancer and 59 cases of lung glandular cancer have gone through pathological con?rmation and all the 104 cases have been put under enhanced scanning on the basis of ?at scanning. The shape and density of the metastatic tumors, encephaledema around the tumors, and the reinforcement change after the enhancement were analyzed. Results: The CT scanning images of all the cases showed that, under ?at scanning, the density of the metastatic tumors to the brain of lung squamous cell cancer was over the slightly-high level and by no means even. Again, under ?at scanning, some 10 cases of metastatic tumors to the brain of lung glandular cancer showed a slightly-high density and some 49 other cases a low density and sack-like low density. Forty-?ve cases of metastatic tumors to the brain of lung squamous cell cancer were with hydroncus while some 30 cases of that of lung glandular cancer were in the same condition. Most of the two types of metastatic tumors, amounting to 97 cases, took place in supratentorial manner, and only 7 cases took place in subtentorial manner. Conclusion: The CT images of metastatic tumors to the brain of lung squamous cell cancer and lung glandular cancer are obviously di?erent from each other. As for the lung squamous cell cancer, the ?at scanning density of the tumor is over the slightly-high level with unevenness. There is relatively obvious reinforcement and obvious hydroncus. As for the lung glandular cancer, the metastatic tumor to the brain shows a low density and sack-like low density under ?at scanning. There is no obvious reinforcement and relatively slight hydroncus.