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[非小细胞肺癌患者肿瘤及肿瘤旁组织中微小RNA let-7a、miR-155和miR-205的表达]

[Expression of microRNA let-7a, miR-155, and miR-205 in tumor and tumor-adjacent histologically normal tissue in patients with non-small cell lung cancer].

作者信息

Shikeeva A A, Kekeeva T V, Zavalishina L E, Andreeva Yu Yu, Zaletaev D V, Frank G A

机构信息

Russian Medical Academy of Postgraduate Education, Ministry of Health of the Russian Federation, Moscow; Research Centre for Medical Genetics, Moscow.

Russian Medical Academy of Postgraduate Education, Ministry of Health of the Russian Federation, Moscow.

出版信息

Arkh Patol. 2016 May-Jun;78(3):3-10. doi: 10.17116/patol20167833-10.

Abstract

UNLABELLED

Non-small cell lung cancer (NSCLC) is a main group of lung malignancies. Epigenetic changes are as important as genome structural changes in carcinogenesis. MicroRNA (miRNA) is a class of non-coding single-stranded RNAs that play an important role in the regulation of matrix RNA (mRNA) translation and degradation. MicroRNA expression changes occur in many cancers. According to the field cancerization theory, tumor-adjacent histologically normal tissue takes part in tumor progression by triggering cell transformation. The important clinical implication is that the fields may serve as the basis for a recurrence after surgery. Thus, the aim of our study was to determine the expression levels of miRNAs let-7a, miR-155, and miR-205 in tumor and tumor-adjacent apparently normal tissues to evaluate these changes as potential prognostic markers in NSCLC patients.

METHODS

The expression of miRNAs let-7a, miR-155, and miR-205 in tumor and tumor-adjacent apparently normal tissues at 2 and 5 cm was determined by real-time PCR with subsequent quantification using a 2-ΔΔСt method. The findings were then analyzed to reveal possible associations with clinical and morphological parameters, such as age, cancer stage, and tumor grade.

RESULTS

The expression of miRNA let-7a was found to be significantly lower in tumor than that in tumor-adjacent apparently normal tissue at 2 and 5 cm. In groups of patients older than 63 years with Stage III-IV NSCLC, the expressions of microRNA let-7a and miR-155 in tumor tissue were substantially lower than that in the adjacent normal tissue. Beyond that point, patients with high-grade tumors had also a significantly lower expression of miRNA let-7a in relatively adjacent apparently normal tissue.

CONCLUSION

The findings suggest that miRNA let-7a and miR-155 may be used as poor prognostic markers for patients with NSCLC.

摘要

未标记

非小细胞肺癌(NSCLC)是肺部恶性肿瘤的主要类型。表观遗传变化在致癌过程中与基因组结构变化同样重要。微小RNA(miRNA)是一类非编码单链RNA,在基质RNA(mRNA)翻译和降解的调控中发挥重要作用。微小RNA表达变化发生在许多癌症中。根据场癌化理论,肿瘤旁组织学正常组织通过触发细胞转化参与肿瘤进展。重要的临床意义在于这些区域可能作为术后复发的基础。因此,我们研究的目的是确定miRNA let-7a、miR-155和miR-205在肿瘤及肿瘤旁明显正常组织中的表达水平,以评估这些变化作为NSCLC患者潜在预后标志物的可能性。

方法

采用实时聚合酶链反应(PCR)并使用2-ΔΔСt法进行后续定量,测定肿瘤及肿瘤旁2厘米和5厘米处明显正常组织中miRNA let-7a、miR-155和miR-205的表达。然后分析这些结果以揭示与临床和形态学参数(如年龄、癌症分期和肿瘤分级)之间可能的关联。

结果

发现肿瘤中miRNA let-7a的表达明显低于2厘米和5厘米处肿瘤旁明显正常组织中的表达。在年龄大于63岁的III-IV期NSCLC患者组中,肿瘤组织中微小RNA let-7a和miR-155的表达明显低于相邻正常组织。除此之外,高级别肿瘤患者相对相邻明显正常组织中miRNA let-7a的表达也明显较低。

结论

这些发现表明,miRNA let-7a和miR-155可能作为NSCLC患者预后不良的标志物。

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