长链非编码RNAAFAP1-AS1在消化系统肿瘤中的表达及意义

Expression of long non-coding RNA AFAP1-AS1 in human digestive system cancer and its clinical significance

目的:探讨长链非编码RNA(long non-coding RNA,lncRNA)肌动蛋白纤维相关蛋白1-反义RNA1(actin filament-associated protein 1-antisense RNA1,AFAP1-AS1)在食管癌、胃癌、肝癌和结直肠癌4种常见消化系统肿瘤组织中的表达情况及其临床意义。方法:采用组织微阵列切片初步筛查82例肿瘤组织(包括食管癌11例、胃癌11例、肝癌26例和结直肠癌34例)及对应癌旁组织中AFAP1-AS1的表达情况。对表达差异明显的肿瘤组织类型(肝癌),再扩大样本量(70例石蜡切片和30例新鲜组织),通过原位杂交和实时荧光定量PCR法进一步检测验证,并分析AFAP1-AS1表达与肝癌主要临床病理特征的相关性,评估其在肿瘤淋巴结转移中的作用。结果:AFAP1-AS1在食管癌中的表达水平高于癌旁组织(P<0.05),在肝癌组织中的表达水平低于癌旁组织(P<0.05),在胃癌和结直肠癌中其表达与癌旁组织中的表达水平没有明显差异(P>0.05)。扩大肝癌组织样本量后,仍然发现肝癌组织中的AFAP1-AS1水平明显下调,并且与临床分期和淋巴结转移有关(P<0.05)。AFAP1-AS1作为肝癌淋巴结转移的分子标志物的灵敏度、特异度、符合度、阳性预测率和阴性预测率分别为91.23%、28.21%、65.62%、68.75%和65.00%。结论:lncRNA AFAP1-AS1可能与肝癌、食管癌的发生和发展有关,并且在肝癌和食管癌中起到不同的生物学作用;AFAP1-AS1可能成为新的肝癌分子标志物,应用于肝癌临床诊断。

Objective： To investigate the expressions of actin filament-associated protein 1 antisense RNA 1 （AFAP1-AS1）, a long non-coding RNA （IncRNA） in four common human digestive system cancers including esophageal cancer, gastric cancer, liver cancer and colorectal cancer, and their clinical significance. Methods： The expression of AFAP1-AS1 was preliminarily detected in several digestive system tumor tissues and their corresponding adjacent normal tissues from 82 cases by multi-tumor tissue microarrays. These 82 patients included 11 with esophageal cancer, 11 with gastric cancer, 26 with liver cancer, and 34 with colorectal cancer. The expression of AFAP1-AS1 which had significant difference in liver tumor tissues was further tested by in situ hybridization （additional 70 cases） and real- time fluorescence quantitative PCR （additional 30 cases）. The relationship between the expression of AFAP1-AS1 and the clinicopathological features was analyzed. The role of AFAP1-AS1 in tumor lymph node metastasis was assessed. Results： The expression of AFAP1-AS1 in liver cancer was significantly lower than that in its corresponding adjacent normal liver tissue （P 〈 0.05）, but this expression was higher in esophageal cancer that in its corresponding adjacent normal esophageal tissue （P 〈 0.05）. The expressions of AFAP1-AS1 in gastric cancer and colorectal cancer were not significantly different from those in their corresponding adjacent normal tissues （P 〉 0.05）. Further test also revealed that the expression of AFAP1 -AS1 was significantly down-regulated in liver cancer, and this effect was associated with clinical stage and lymph node metastasis （P 〈 0.05）. The sensitivity, specificity, coincidence rate, positive predictive value and negative predictive value of AFAP1-AS1 serving as a molecular marker of metastasis were 68.75%, 65.00%, 65.63%, 28.21% and 91.23%, respectively. Conclusion： The expression of AFAP1-AS1 may play a role in the pathogenesis and progression of liver cancer and esophageal cancer, but this effect is different between these two cancer types. It is suggested that AFAP1-AS1 may become a noval molecular marker for clinical diagnosis of liver cancer.