Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
J Cancer Res Clin Oncol. 2011 Apr;137(4):557-66. doi: 10.1007/s00432-010-0918-4. Epub 2010 May 28.
This study compared miRNA expression patterns in primary squamous cell lung carcinoma specimens with those of matched normal lung tissue in order to determine their potential relevance to clinicopathological factors and patient postoperative survival times.
Locked nucleic acids miRNA microarray expression profiling was performed on four matched pairs of tissues. After microarray validation by quantitative real-time reverse transcription polymerase chain reaction assays (qRT-PCR) (real-time PCR), miR-21 was selected for further TaqMan real-time PCR study in 30 matched tissue pairs.
Seven miRNAs of hsa-miR-21, hsa-miR-31, hsa-miR-34a, hsa-miR-22*, hsa-miR-504, hsa-miR-18a, and hsa-miR-412 were observed to be upregulated greater than twofold in the squamous cell lung carcinoma tissues compared with normal tissues, whereas 23 miRNAs of hsa-miR-30a, hsa-miR-30d, hsa-miR-126, hsa-miR-652, hsa-miR-100, hsa-miR-143, hsa-miR-130a, hsa-miR-145, hsa-miR-30e, hsa-miR-126*, hsa-miR-181a, hsa-miR-125b, hsa-miR-886-3p, hsa-miR-451, hsa-miR-29c, hsa-miR-26b, hsa-miR-101, hsa-miR-320, hsa-miR-30b, hsa-miR-886-5p, hsa-miR-29a, hsa-miR-26a, and hsa-miR-99a were found to be downregulated greater than twofold. MiR-21 was overexpressed in 73.3% of the squamous cell lung carcinoma specimens examined (P = 0.022). The relationship between the miR-21 expression level and various clinicopathologic factors was also analyzed. High-level expression of miR-21 was significantly correlated with shortened survival time (P = 0.022, log-rank test; Kaplan-Meier). Multivariate Cox proportional hazard regression analysis revealed this significant prognostic impact (P = 0.000; HR 1.293; 95% CI 1.123-1.489) to be independent of clinical disease stage (P = 0.013; HR 2.660; 95% CI 1.229-5.758) and other clinicopathologic factors.
Expression patterns of miRNAs were found to be systematically altered in squamous cell lung carcinoma tissue. High miR-21 expression is associated with shortened survival time, indicating that miR-21 may serve as a molecular diagnostic and prognostic marker for patients with squamous cell lung carcinoma.
本研究比较了原发性肺鳞癌组织与匹配的正常肺组织中 miRNA 的表达模式，以确定其与临床病理因素和患者术后生存时间的潜在相关性。
对四对组织进行了锁核酸 miRNA 微阵列表达谱分析。通过定量实时逆转录聚合酶链反应（qRT-PCR）（实时 PCR）验证微阵列后，选择 miR-21 进行进一步的 30 对匹配组织的 TaqMan 实时 PCR 研究。
与正常组织相比，hsa-miR-21、hsa-miR-31、hsa-miR-34a、hsa-miR-22*、hsa-miR-504、hsa-miR-18a 和 hsa-miR-412 等 7 种 miRNA 在鳞状细胞肺癌组织中表达上调两倍以上，而 hsa-miR-30a、hsa-miR-30d、hsa-miR-126、hsa-miR-652、hsa-miR-100、hsa-miR-143、hsa-miR-130a、hsa-miR-145、hsa-miR-30e、hsa-miR-126*、hsa-miR-181a、hsa-miR-125b、hsa-miR-886-3p、hsa-miR-451、hsa-miR-29c、hsa-miR-26b、hsa-miR-101、hsa-miR-320、hsa-miR-30b、hsa-miR-886-5p、hsa-miR-29a、hsa-miR-26a 和 hsa-miR-99a 等 23 种 miRNA 的表达下调两倍以上。miR-21 在 73.3%的鳞状细胞肺癌标本中过表达（P = 0.022）。还分析了 miR-21 表达水平与各种临床病理因素之间的关系。miR-21 的高表达与生存时间缩短显著相关（P = 0.022，对数秩检验； Kaplan-Meier）。多变量 Cox 比例风险回归分析显示，这一显著的预后影响（P = 0.000；HR 1.293；95%CI 1.123-1.489）独立于临床疾病分期（P = 0.013；HR 2.660；95%CI 1.229-5.758）和其他临床病理因素。
在鳞状细胞肺癌组织中发现 miRNA 的表达模式发生了系统性改变。高 miR-21 表达与生存时间缩短相关，表明 miR-21 可能作为鳞状细胞肺癌患者的分子诊断和预后标志物。
