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载脂蛋白 C1(APOC1)作为一种新型肺癌诊断和预后生物标志物的研究:标志物Ⅰ期临床试验。

Apolipoprotein C1 (APOC1) as a novel diagnostic and prognostic biomarker for lung cancer: A marker phase I trial.

机构信息

Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital Taipei, Taiwan.

Division of Chest Medicine, Shin Kong Wu Ho-Su Memorial Hospital Taipei, Taiwan.

出版信息

Thorac Cancer. 2014 Nov;5(6):500-8. doi: 10.1111/1759-7714.12117. Epub 2014 Oct 23.

Abstract

BACKGROUND

Tumor cells continuously evolve over time in response to host pressures. However, explanations as to how tumor cells are influenced by the inflammatory tumor microenvironment over time are, to date, poorly defined. We hypothesized that prognostic biomarkers could be obtained by exploring the expression of inflammation-associated genes between early and late stage lung cancer tumor samples.

METHODS

Candidate inflammation-associated genes, apolipoprotein C-1 (APOC1), MMP1, KMO)1, CXCL5, CXCL)7, IL-1α, IL-1β, TNF-α and IL-6 were verified by real-time quantitative polymerase chain reaction. Gene expression profiles and immunofluorescence staining of 30 lung cancer tissues were compared.

RESULTS

Expressions of APOC1 and IL-6 mRNA on tumor tissues in late stage disease were significantly higher than in early stage lung cancer samples. Immunofluorescence staining of tumor samples showed that the expression of APOC1 gradually increased from early to late stage in lung cancer patients. The expression levels of IL-6 and APOC1 in tumor samples were positively correlated; however, no prognostic value of APOC1 can be identified in serum samples.

CONCLUSIONS

We found that the level of tumor APOC1 was highly expressed in late stage lung cancer. Further research is warranted to determine the molecular mechanisms underlying the cross talk of APOC1 and IL-6 in tumor progression. An expanded sample size marker phase II study may lead to the discovery of new lung cancer therapeutics targeting APOC1.

摘要

背景

肿瘤细胞会持续进化以应对宿主压力。然而,迄今为止,关于肿瘤细胞如何随时间受到炎症肿瘤微环境影响的解释还很不清楚。我们假设通过探索早期和晚期肺癌肿瘤样本中炎症相关基因的表达,可以获得预后生物标志物。

方法

通过实时定量聚合酶链反应验证候选炎症相关基因(载脂蛋白 C-1 [APOC1]、MMP1、KMO1、CXCL5、CXCL7、IL-1α、IL-1β、TNF-α和 IL-6)。比较了 30 例肺癌组织的基因表达谱和免疫荧光染色。

结果

晚期疾病肿瘤组织中 APOC1 和 IL-6mRNA 的表达明显高于早期肺癌样本。肿瘤样本的免疫荧光染色显示,APOC1 在肺癌患者中从早期到晚期逐渐增加。肿瘤样本中 IL-6 和 APOC1 的表达水平呈正相关;然而,在血清样本中无法确定 APOC1 的预后价值。

结论

我们发现晚期肺癌中肿瘤 APOC1 的水平高度表达。需要进一步研究以确定 APOC1 和 IL-6 在肿瘤进展中的相互作用的分子机制。扩大样本量的 II 期标志物研究可能会发现针对 APOC1 的新的肺癌治疗方法。

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