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首页> 外文期刊>Lung cancer: Journal of the International Association for the Study of Lung Cancer >Quantitative analysis of carbonic anhydrase IX mRNA in human non-small cell lung cancer.
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Quantitative analysis of carbonic anhydrase IX mRNA in human non-small cell lung cancer.

机译:第九碳酸酐酶的定量分析mRNA在人非小细胞肺癌。

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摘要

Hypoxia is associated with malignant progression and poor outcome in human cancers. The effects of hypoxia are mediated by a series of genomic changes that enable tumor cells to survive or escape their oxygen deficient environment. Recent studies indicated that carbonic anhydrase IX (CA IX) is an intrinsic marker of hypoxia. In the present study we investigated with quantitative RT-PCR the expression of CA IX mRNA in 93 non-small cell lung carcinomas (NSCLC) and in their paired not affected tissues. CA IX mRNA was expressed in 100% NSCLC and in 76% of paired not affected tissues, even if tumoral CA IX expression was found constantly higher (p < 0.02) than that found in normal tissues. The increase of CA IX mRNA expression in cancer tissues was significantly correlated to the increase of corresponding protein, as determined with conventional immunoblotting (p = 0.027). In addition the expression of CA IX mRNA in NSCLC samples was significantly correlated to VEGF (p = 0.002) and MMP-9 (p = 0.002) mRNAs. Whereas CA IX mRNA expression was not associated to any clinical-pathological parameters in our patients, global survival analysis of cancer-related death revealed that high expression of CA IX mRNA predicted unfavorable outcome (p = 0.001) and shorter disease free survival interval (p = 0.004). A multivariate analysis showed that CA IX expression was the strongest prognostic parameter (p = 0.000) in comparison to other conventional predictive markers. In addition, differences emerged on the basis of clinical-pathological parameters: in fact separate Kaplan-Meyer analyses of patients indicated that whereas high levels of CA IX mRNA expression were not predictive of worse prognosis in early NSCLC (G1, T1, Stage 1 and pN- patients), this parameter appeared highly significant in advanced NSCLC (G2-G3, T2-T3, Stage 2-3 and pN+ patients). Finally we demonstrated that CA IX expression was not able to discriminate different survival probability in adenocarcinomas, whereas the same parameter was highly predictive in squamous (p = 0.03) and adenosquamous cell carcinomas (p = 0.001).
机译:缺氧与恶性进展相关在人类癌症和糟糕的结果。缺氧是由一系列的基因使肿瘤细胞生存或变化摆脱氧气不足的环境。研究表明第九碳酸酐酶(CAIX)是一种内在的缺氧的标志。本研究我们和定量研究rt - pcr CA 93年第九mRNA的表达肺非小细胞癌(NSCLC)和他们的搭配不是影响组织。表示在100%的非小细胞肺癌和76%的配对受影响的组织,即使tumoral CA第九表达式被发现不断更高(p < 0.02)比正常组织中找到。对癌症组织CA IX mRNA表达的的增加显著相关相应的蛋白,确定传统的免疫印迹(p = 0.027)。除了第九CA mRNA的表达在非小细胞肺癌样品VEGF呈显著相关(p =0.002)和MMP-9 mrna (p = 0.002)。信使rna表达任何无关在我们的病人clinical-pathological参数,全球癌症相关死亡的生存分析显示高CA IX mRNA的表达预测结果(p = 0.001)和不利无病生存时间短(p =0.004)。表达式是最强的预测参数(p = 0.000)相比其他传统预测标记。出现在clinical-pathological的基础参数:事实上Kaplan-Meyer分开病人的分析表明,而高CA IX mRNA表达水平预测早期非小细胞肺癌的预后差(G1,T1,阶段1和pN -病人),此参数出现在晚期非小细胞肺癌非常重要(T2-T3 G2-G3阶段2 - 3和pN +病人)。最后,我们证明了CA第九表达式不能区分不同的生存在腺癌的概率,而相同的参数在鳞状上皮(p =高度预测0.03)和adenosquamous细胞癌(p =0.001).

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