长链非编码RNA LINC00152在结肠癌组织中的表达及临床意义

Expression of long non-coding RNA LINC00152 in human colon cancer and its clinical significance

目的探讨长链非编码RNA LINC00152在结肠癌组织中的原位表达情况及其临床意义。方法用微阵列显著性分析（significance analysis of microarrays,SAM）软件分析下载于NCBI GEO数据库的基因芯片GSE33113数据,筛选结肠癌中差异表达的lncRNA;原位杂交法检测LINC00152在115例结肠癌及其癌旁组织中的表达状况;分析LINC00152阳性率与结肠癌临床病理参数的关系,并用受试者工作曲线（receiver operating characteristics,ROC）评估其作为肿瘤转移、预后预测分子标志物的潜在应用价值。结果 SAM软件分析基因芯片数据发现,结肠癌组织中共有65个lncRNA差异表达（P均〈0.01）,其中上调lncRNA（倍数变化〉2）6个,下调lncRNA（倍数变化〈0.5）59个;原位杂交结果显示,LINC00152在结肠癌和癌旁组织中的阳性率分别为63.48%（73/115）和9.57%（11/115）,两者差异有统计学意义（χ^2=72.091,P〈0.05）。临床Ⅰ期、Ⅱ期结肠癌组织中LINC00152的阳性率（27.78%和45.28%）明显低于Ⅲ~Ⅳ期（77.27%）,差异有统计学意义（χ^2分别为10.234和13.411,P〈0.05）,发生淋巴结转移的结肠癌组织中LINC00152的阳性率（81.13%）明显高于非淋巴结转移者（48.39%）,差异有统计学意义（χ^2=13.215,P〈0.05）。LINC00152对结肠癌患者淋巴结转移诊断的ROC曲线下面积（AUCROC）为0.771（95%CI：0.588~0.834,P〈0.01）,当cut off值为3.1时,其敏感性为72.1%、特异性为65.4%、约登指数为0.375。结论LINC00152在结肠癌组织中表达增高,且与临床分期和淋巴结转移有关,可能作为结肠癌转移评估的分子标志物。

Objective To investigate the expression of long non-coding RNA（ lncRNA） LINC00152 in colon cancer and its clinical significance. Methods The significance analysis of microarrays（ SAM） software was used to analyze the data of gene microarray GSE33113 which was downloaded from NCBI GEO Data Sets,and differential expression of lncRNA in colon cancer was screened. The expressions of LINC00152 in 115 cases of colon cancer and its adjacent normal tissues were detected by in situ hybridization（ ISH）.Then,the correlation between LINC00152 expression and clinicopathological characteristics of colon cancer was analyzed,and the potential value of LINC00152 in predicting the metastasis and prognosis of colon cancer was evaluated by receiver operating characteristics（ ROC） analysis. Results Analysis of gene microarray GSE33113 data by SAM found 65 differentially expressed lncRNA in colon cancer,including 6 up-regulated lncRNA（ fold change〉 2） and 59 down-regulated lncRNA（ fold change 0. 5）. The results of in situ hybridization showed that the positive rates of LINC00152 in colon carcinoma tissues and their adjacent non-cancerous tissues were63. 48%（ 73 /115） and 9. 57%（ 11 /115）,respectively,with significant difference between them（ χ2= 72. 091,P〈0. 05）. The positive rate of LINC00152 in clinical stage T3 or T4（ 77. 27%） was significantly higher than that in clinical stages T1（ 27. 78%,χ^2= 10. 234,P〈0. 05） and T2（ 45. 28%,χ^2= 13. 411,P〈0. 05）. Moreover,the positive rate of LINC00152 in colon cancer patients with lymph node metastasis（ 81. 13%） was significantly higher than that without lymph node metastasis（ 48. 39%,χ2=13. 215,P〈0. 05）. When LINC00152 was used to diagnose the patients with lymph node metastasis,the area under the ROC curve（ AUC^ROC） was 0. 771（ 95% CI： 0. 588-0. 834,P〈0. 01）. When the cut-off value was set as 3. 1,the sensitivity and specificity were 72. 1% and 65. 4%,respectively,and Youden index was 0. 375. Conclusion There was increased expression of LINC00152 in colon cancer tissues,which was related to clinical stages and lymph node metastasis of colon cancer,indicating that LINC00152 might be used as a new molecular biomarker for evaluating the metastasis and prognosis of colon cancer.