Chen Cheng, Zhu Wei-Dong, Xie Fang, Huang Jian-An
Respiratory Department, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Pathology Department, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Oncotarget. 2016 Sep 6;7(36):58563-58568. doi: 10.18632/oncotarget.10542.
Although the pathogenicity of B7-H4 in cancer is well established, its role in pulmonary adenocarcinoma, especially lesions presenting as solitary pulmonary nodules (SPNs), remains unclear.
40 cases of pulmonary adenocarcinoma presenting with SPN were enrolled during year 2012-2015. The B7-H4 expression and its subcellular distribution in pulmonary adenocarcinoma presenting with SPN were analyzed by immunohistochemistry, further its correlation with Ki-67 expression and CT feature. In vitro, the B7-H4 expression in the cytoplasmic and nucleus fractions of lung cancer cell lines was determinate by western blotting.
Immunostaining revealed B7-H4 in the cytoplasm of cells from all 40 SPN samples studied. No surface localization of B7-H4 was detected, but in 18 samples the nuclear membranes were B7-H4-positive. Moreover, patients with more poorly differentiated and invasive adenocarcinomas showed greater localization of B7-H4 to the nuclear membrane. The percentage of lesions with ground-glass opacity was significantly greater among samples negative for nuclear membrane B7-H4. Most importantly, there was a statistically significant relationships between the Ki-67 index and B7-H4 positivity of the nuclear membrane. This suggests tumors exhibiting higher nuclear membrane B7-H4 have greater proliferative potential. Western blotting confirmed both cytoplasmic and nuclear B7-H4 localization in lung adenocarcinoma cell lines.
Taken together, our study provides a new insight into the tumorigenicity of B7-H4 in lung adenocarcinoma. We suggest that in pulmonary adenocarcinoma presenting with SPN, nuclear membrane localization of B7-H4 within the tumor cells is associated with increased malignancy.
尽管B7-H4在癌症中的致病性已得到充分证实，但其在肺腺癌，尤其是表现为孤立性肺结节（SPN）的病变中的作用仍不清楚。
纳入2012年至2015年期间40例表现为SPN的肺腺癌患者。采用免疫组织化学方法分析B7-H4在表现为SPN的肺腺癌中的表达及其亚细胞分布，进一步分析其与Ki-67表达及CT特征的相关性。体外实验中，通过蛋白质免疫印迹法测定肺癌细胞系细胞质和细胞核组分中B7-H4的表达。
免疫染色显示，在所有研究的40个SPN样本的细胞胞质中均检测到B7-H4。未检测到B7-H4的表面定位，但在18个样本中核膜呈B7-H4阳性。此外，分化程度越低、侵袭性越强的腺癌患者，B7-H4在核膜上的定位越明显。核膜B7-H4阴性的样本中磨玻璃影病变的比例明显更高。最重要的是，Ki-67指数与核膜B7-H4阳性之间存在统计学显著关系。这表明核膜B7-H4表达较高的肿瘤具有更大的增殖潜能。蛋白质免疫印迹法证实了肺癌细胞系中B7-H4在细胞质和细胞核中的定位。
综上所述，我们的研究为B7-H4在肺腺癌中的致瘤性提供了新的见解。我们认为，在表现为SPN的肺腺癌中，肿瘤细胞内B7-H4的核膜定位与恶性程度增加有关。
