Overexpression of periostin predicts poor prognosis in non-small cell lung cancer.
Overexpression of periostin predicts poor prognosis in non-small cell lung cancer.
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DOI：
10.3892/ol.2013.1590
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发表时间：
2013-12
期刊：
影响因子：
2.9
通讯作者：
Shi Y
中科院分区：
文献类型：
--
作者：
Hong LZ;Wei XW;Chen JF;Shi Y
由 POSTN 基因编码的骨膜素蛋白是细胞外基质的组成部分，由成纤维细胞表达，并已在多种人类恶性肿瘤中观察到。本研究旨在检测非小细胞肺癌（NSCLC）患者和良性肺部肿瘤组织中骨膜素的表达，并将结果与受试者的临床病理数据相关联，以评估骨膜素作为潜在的预后标志物。本研究总共纳入了 49 名 NSCLC 患者和 6 名良性肺部肿瘤患者。通过蛋白质印迹分析检测配对的正常/肿瘤旁/癌症组织中骨膜素的蛋白质水平，并通过定量聚合酶链反应（qPCR）检测配对的正常/癌症组织中的mRNA水平。然后将结果与已确定的生物学和预后因素相关联。使用免疫组织化学来确认非小细胞肺癌组织中骨膜蛋白的位置。使用 Cox 比例风险回归模型进行单变量和多变量分析。与正常组织（P=0.017）和癌旁组织（P=0.000）相比，NSCLC患者癌组织中periostin蛋白水平升高。男性患者中蛋白质（P=0.001）和mRNA（P=0.010）水平的表达水平远高于女性患者。非腺癌（non-ADC）患者的mRNA水平远高于腺癌（ADC）患者（P=0.029）。 Periostin在假瘤和结核病患者中的蛋白水平表达高于邻近组织（P=0.016）和周围组织（P=0.001）。免疫染色表明间充质区域存在高水平的骨膜素，但癌细胞本身不存在。表现出高水平骨膜蛋白表达的肿瘤患者的生存时间显着缩短（P=0.036，对数秩检验）。低水平骨膜素表达的患者（periostin-L；n=27）的3年生存率为81.5%，高水平骨膜素表达的患者（periostin-H；n=22）的3年生存率为45.4%。同样，病理淋巴结 (pN) 状态是单变量 Cox 生存分析中的重要预后标志。值得注意的是，通过多变量分析，periostin-H 表达也被确定为独立的预后因素（P=0.011）。这些结果表明periostin的过度表达预示着不良预后，因此它可能被视为NSCLC进展和发展中的新分子。该结果为NSCLC的辅助治疗提供了额外的靶点。
The periostin protein, encoded by the POSTN gene, is a component of the extracellular matrix, which is expressed by fibroblasts and has been observed in a variety of human malignancies. The present study aimed to detect the expression of periostin in the tissues of non-small cell lung cancer (NSCLC) patients and benign lung tumors, and to correlate the results with the clinicopathological data of the subjects, in order to evaluate periostin as a potential prognostic marker. In total, 49 NSCLC patients and 6 benign lung tumors were included in this study. The protein level of periostin was detected in paired normal/paratumor/cancer tissues by a western blot analysis and the mRNA level in paired normal/cancer tissues was detected by quantitative polymerase chain reaction (qPCR). The results were then correlated with established biological and prognostic factors. Immunohistochemistry was used to confirm the location of periostin in the NSCLC tissues. Uni- and multivariate analyses were performed using Cox’s proportional hazards regression model. The protein level of periostin was elevated in the cancer tissue of the NSCLC patients compared with the normal (P=0.017) and paratumor (P=0.000) tissues. The expression level in the male patients was much higher than in the female patients at the protein (P=0.001) and mRNA (P=0.010) levels. The mRNA level in the non-adenocarcinoma (non-ADC) patients was much higher than in the adenocarcinoma (ADC) patients (P=0.029). Periostin was demonstrated higher expression at the protein level in the pseudotumors and tuberculosis patients than in the adjacent (P=0.016) and surrounding tissues (P=0.001). Immunostaining indicated that high levels of periostin were present in the mesenchymal areas, but not in the cancer cells themselves. The patients with tumors exhibiting high-level periostin expression showed a significantly shorter survival time (P=0.036, log-rank test). The 3-year survival rate was 81.5% for patients with low-level periostin expression (periostin-L; n=27) and 45.4% for patients with high-level periostin expression (periostin-H; n=22). Similarly, pathological node (pN) status was a significant prognostic marker in the univariate Cox survival analysis. Notably, periostin-H expression was also identified as an independent prognostic factor by the multivariate analysis (P=0.011). These results showed that the overexpression of periostin predicts a poor prognosis, therefore it may be regarded as a novel molecule in the progression and development of NSCLC. The results provide an additional target for the adjuvant treatment of NSCLC.
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