The serine protease HtrA1 is a novel prognostic factor for human mesothelioma
The serine protease HtrA1 is a novel prognostic factor for human mesothelioma
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DOI：
10.2217/14622416.9.8.1069
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发表时间：
2008-08-01
期刊：
影响因子：
2.1
通讯作者：
Facciolo, Francesco
中科院分区：
文献类型：
--
作者：
Baldi, Alfonso;Mottolese, Marcella;Facciolo, Francesco
目的：本研究的目的是分析70例恶性间皮瘤中丝氨酸蛋白酶HtrA1和EGFR表达的潜在预后价值。材料与方法：采用免疫组化法检测HtrA1和EGFR的表达。单变量和多变量分析用于将这些分子因子的表达与可用的临床病理数据与患者生存相关联。结果：HtrA1表达水平与生存率呈正相关，有统计学意义（p < 0.0001）。相比之下，EGFR表达与生存率呈负相关（p = 0.02）。此外，肿瘤的延伸(T)和淋巴结的受累(N)、晚期状态（分别为p = 0.001和0.002）以及肉瘤样组织型（p = 0.005）与生存率差显著相关。最后，通过多变量Cox回归分析，唯一导致影响总生存率的免疫组织化学参数是HtrA1 （p = 0.0001）。有趣的是，HtrA1表达的预后价值完全独立于EGFR表达（p < 0.0001）。结论：本研究首次探讨了间皮瘤患者HtrA1表达与生存的关系。所获得的数据强烈表明HtrA1表达可作为间皮瘤的预后参数，并提示这种丝氨酸蛋白酶可能是治疗恶性间皮瘤的分子靶点。
Aims: The objective of our study was to analyze the potential prognostic value of the expression of the serine protease HtrA1 and of EGFR in 70 malignant mesotheliomas. Materials & methods: Immunohistochemistry was used to determine the expression of HtrA1 and EGFR. Univariate and multivariate analyses were used to correlate expression of these molecular factors in combination with available clinicopathologic data to patient survival. Results: A positive, statistically significant relationship has been recorded between HtrA1 expression level and survival (p < 0.0001). By contrast, a negative relationship has been identified between EGFR expression and survival (p = 0.02). Moreover, extension of the tumor (T) and involvement of lymph nodes (N) advanced status (p = 0.001 and 0.002, respectively), as well as the sarcomatoid histotype (p = 0.005), correlated significantly with poor survival. Finally, by a multivariate Cox regression analysis, the only immuncihistochemical parameter that resulted to influence overall survival was HtrA1 (p = 0.0001). interestingly, the prognostic value of HtrA1 expression was completely independent from EGFR expression (p < 0.0001). Conclusion: This is the first study of the relationship between HtrA1 expression and survival of mesothelioma patients. The data obtained strongly indicate the utilization of HtrA1 expression as a prognostic parameter for mesothelioma and suggest this serine protease as a possible molecular target for the treatment of malignant mesotheliomas.