长链非编码RNA BC200在非小细胞肺癌患者组织中的表达及作用*

摘要

Objective: To investigate the expression level and clinical significance of a long non-coding RNA (LncRNA), BC200 in non-small cell lung cancer (NSCLC) and analyze its correlation with the epithelial-mesenchymal transition (EMT)-related proteins, E-cad-herin, N-cadherin, and Snail. Methods: Sixty NSCLC and sixty paired adjacent tissue samples were collected to detect the BC200 levels. Furthermore, 40 samples of NSCLC and 40 samples of normal lung tissues were collected to quantify the messenger RNA (mRNA) lev-els of E-cadherin, N-cadherin, and Snail using quantitative polymerase chain reaction. The relationship between the BC200 level and mRNA levels of E-cadherin, N-cadherin, and Snail was explored in NSCLC tissues. The correlation between BC200 and clinical pathologi-cal parameters (gender, age, TNM stage, tumor size, lymph node metastasis, and pathologic type) was also analyzed. Receiver operat-ing characteristic curve (ROC) was constructed to evaluate the diagnostic efficiency of BC200. Immunohistochemical staining was per-formed to determine the expression levels of E-cadherin, N-cadherin, and Snail in 40 specimens of NSCLC and 20 specimens of normal lung tissue and their correlation to the expression levels of BC200 was evaluated. Results: 1) The expression of BC200, N-cadherin mRNA, and Snail mRNA was significantly upregulated in the tumor tissues when compared to that in normal lung tissues (P<0.05). The expression of E-cadherin mRNA was significantly lower in tumor tissues than in the normal lung tissues (P<0.05). 2) The positive rate of E-cadherin, N-cadherin, and Snail in NSCLC was 40% (16/40) , 57.5% (23/40), and 57.5% (23/40), respectively, while that of normal lung tissues was 95% (19/20), 5% (1/20), and 10% (2/20), respectively. There was a significant difference between these two data sets (P<0.05). 3) BC200 is highly expressed in the NSCLC tissues. The high expression of BC200 in lung cancer was correlated with lymph node metastasis, clinical stage, and positive rate of E-cadherin, N-cadherin, and Snail. The expression of BC200 in NSCLC tissues was negatively correlated with the expression of E-cadherin mRNA (r=-0.31, P<0.05) and positively correlated with the expression of Snail and N-cadherin mRNA (r=0.305, r=0.257, P<0.05). 4) ROC analysis of BC200 indicated a potential diagnostic value of BC200 levels in NSCLC . Conclusions: BC200 is highly expressed in NSCLC tissues, which was correlated with lymph node metastasis, clinical stage, E-cadherin, N-cadherin, and Snail positive rate. The expression of BC200 in NSCLC tissues was negatively correlated with E-cadherin and positively correlated with Snail and N-cadherin. BC200 may regulate the invasion and migration ability of NSCLC by EMT. BC200 may be a potential tumor marker for NSCLC diagnosis.%目的:分析长链非编码RNA(long non-coding RNA,lncRNA)BC200在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中的表达情况,并探讨其临床意义及其与上皮-间质转化(epithelial-mesenchymal transition,EMT)相关蛋白E-cadherin、N-cadherin及Snail之间的关系.方法:采用实时荧光定量PCR(QPCR)法检测2014年1月至2018年6月天津市胸科医院60例癌组织及60例对应的正常肺组织中BC200表达情况,40例癌组织及40例正常肺组织中E-cadherin、N-cadherin及Snail mRNA表达水平,统计分析NSCLC中BC200与E-cadherin、N-cadherin及Snail mRNA表达水平以及两者的相关性,分析BC200与临床病理特征(性别、年龄、TNM分期、肿瘤大小、淋巴结转移及病理类型水平)的关系,应用受试者工作特征(receiver operating characteristic curve,ROC)曲线鉴别诊断NSCLC的效能;采用免疫组织化学法检测E-cadherin、N-cadherin及Snail蛋白在40例NSCLC组织及20例正常肺组织中表达情况,分析其与BC200表达情况的关系.结果:1)肺癌组织中的BC200、N-cadherin及Snail mRNA的表达水平显著高于正常肺组织中的表达水平(P<0.05),E-cadherin mRNA的表达量低于正常肺组织(P<0.05);2)E-cadherin、N-cadherin及Snail在NSCLC组织中阳性表达率分别为40.0%(16/40)、57.5%(23/40)、57.5%(23/40),在正常肺组织中的阳性表达率为95%(19/20)、5%(1/20)、10%(2/20),表达差异具有统计学意义(P<0.05);3)肺癌组织中BC200的高表达与淋巴结转移、临床分期、E-cadherin、N-cadherin及Snail阳性率相关(P<0.05),BC200的表达与E-cadherin mRNA的表达呈负相关(r=-0.31,P<0.05),与Snail、N-cadherin mRNA的表达呈正相关(r=0.305、r=0.257,P<0.05);4)ROC曲线分析表明,组织lncRNA表达水平对NSCLC的诊断敏感度和特异度均较满意.结论:BC200在NSCLC组织中高表达,且与淋巴结转移、临床分期、E-cadherin、N-cadherin及Snail阳性率相关,BC200的表达与E-cadherin mRNA的表达呈负相关,与Snail、N-cadherin mRNA的表达呈正相关,提示BC200可能通过上皮间质转化调节肺癌细胞侵袭和迁移能力.在NSCLC诊断上,lncRNA BC200水平有较高的价值,可考虑作为NSCLC诊断的潜在标记物.