Liu Jiang-Hua, Chen Gang, Dang Yi-Wu, Li Chun-Jun, Luo Dian-Zhong
Department of Emergency, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China E-mail :
Asian Pac J Cancer Prev. 2014;15(7):2971-7. doi: 10.7314/apjcp.2014.15.7.2971.
Long non-coding RNAs (lncRNAs) have been recently observed in various human cancers. However, the role of lncRNAs in pancreatic duct adenocarcinoma (PDAC) remains unclarified. The aim of this study was to detect the expression of lncRNA MALAT1 in PDAC formalin-fixed, paraffin embedded (FFPE) tissues and to investigate the clinical significance of the MALAT1 level.
The expression of MALAT1 was examined in 45 PDAC and 25 adjacent non-cancerous FFPE tissues, as well as in five PDAC cell lines and a normal pancreatic epithelium cell line HPDE6c-7, using qRT-PCR. The relationship between MALAT1 level and clinicopathological parameters of PDAC was analyzed with the Kaplan-Meier method and Cox proportional hazards model.
The relative level of MALAT1 was significantly higher in PDAC compared to the adjacent normal pancreatic tissues (p=0.009). When comparing the MALAT1 level in the cultured cell lines, remarkably higher expression of MALAT1 was found in aspc-1 PDAC cells compared with the immortal pancreatic duct epithelial cell line HPDE6c-7 (q=7.573, p<0.05). Furthermore, MALAT1 expression level showed significant correlation with tumor size (r=0.35, p=0.018), tumor stage (r=0.439, p=0.003) and depth of invasion (r=0.334, p=0.025). Kaplan-Meier analysis revealed that patients with higher MALAT1 expression had a poorer disease free survival (p=0.043). Additionally, multivariate analysis indicated that overexpression of MALAT1, as well as the tumor location and nerve invasion, was an independent predictor of disease-specific survival of PDAC.
MALAT1 might be considered as a potential prognostic indicator and may be a target for diagnosis and gene therapy for PDAC.
长链非编码RNA(lncRNAs)最近在多种人类癌症中被发现。然而,lncRNAs在胰腺导管腺癌(PDAC)中的作用仍不清楚。本研究的目的是检测lncRNA MALAT1在PDAC福尔马林固定、石蜡包埋(FFPE)组织中的表达,并探讨MALAT1水平的临床意义。
采用qRT-PCR检测45例PDAC和25例相邻非癌FFPE组织以及5种PDAC细胞系和1种正常胰腺上皮细胞系HPDE6c-7中MALAT1的表达。用Kaplan-Meier法和Cox比例风险模型分析MALAT1水平与PDAC临床病理参数的关系。
与相邻正常胰腺组织相比,PDAC中MALAT1的相对水平显著更高(p=0.009)。在比较培养细胞系中的MALAT1水平时,发现与永生化胰腺导管上皮细胞系HPDE6c-7相比,aspc-1 PDAC细胞中MALAT1的表达明显更高(q=7.573,p<0.05)。此外,MALAT1表达水平与肿瘤大小(r=0.35,p=0.018)、肿瘤分期(r=0.439,p=0.003)和浸润深度(r=0.334,p=0.025)显著相关。Kaplan-Meier分析显示,MALAT1表达较高的患者无病生存期较差(p=0.043)。此外,多变量分析表明,MALAT1的过表达以及肿瘤位置和神经侵犯是PDAC疾病特异性生存的独立预测因素。
MALAT1可能被视为一种潜在的预后指标,可能是PDAC诊断和基因治疗的靶点。