HCC 1ncRNA Expression Profiling Studies

BackgroundHepatocellular carcinoma （HCC） is the sixth most prevalent neoplasm and the third leading cause of cancer-related death. Especially, the new cases of HCC in China account for almost55%of all patients worldwide. With a dismal5-year survival rate of approximately5-6%, HCC is still one of the cancers with the worst prognosis and causes enormous social cost and burden. The carcinogenic process of HCC involves synergetic effects of multiple genetic and environmental factors, requires various pathologic stages and engages a number of molecular events. There is a great need for elucidating the relationships between clinicopathological features and molecular changes in HCC to develop new diagnosis and treatment strategies and improve the prognosis of diagnosed patients.In recent years, long non-coding RNAs （lncRNAs） have been shown to possess prominent and diverse regulatory functions in cancer processes. However, the roles of lncRNAs in hepatocellular carcinoma （HCC） and their clinical significances remain largely unknown.ObjectiveThe aim of this study was to exploit human lncRNA microarray for comprehensive and quantitative analyses of lncRNAs expression profiles in paired HCC tissues and adjacent non-tumor （NT） liver tissues and to evaluate the feasibility of using tissue lncRNAs as novel biomarker for the detection of HCC.MethodsThis was a retrospective laboratory study in a tertiary-referral university hospital in Beijing, PR China, between March2011and July2013. Twenty-nine subjects with histologically proven HCC were enrolled in this study. Liver resection was performed for each patient, and tissue samples were collected immediately after operation. Microarray-based lncRNAs expression profiling was used to identify differentially expressed lncRNAs between HCC tissues and adjacent non-tumor （NT） liver tissues, and quantification of selected lncRNAs was performed using quantitative real-time polymerase chain reaction （qRT-PCR）.Results659lncRNAs were differentially expressed between HCC tissues and NT tissues, of which five lncRNAs （TCONS₀0018278, AK093543, D16366, ENST00000501583, NR₀02819（MALAT1）） were selected for validation. Four of them were significantly down-regulated in HCC tissues compared with NT tissues （P=0.012,0.045,0.000and0.000, respectively）, and the expression level of MALAT1showed no significant difference （P=0.114）. ConclusionThis study reveals a set of lncRNAs differentially expressed in HCC tissues and provides useful information for exploring potential therapeutic targets and diagnostic biomarkers of this malignance. TCONS₀0018278, AK093543, D16366and ENST00000501583are down-regulated in HCC tissues and have the potential to be valuable biomarkers for diagnosing HCC. Further validations of the role of MALAT1in HCC are necessary.