标题：Identification of a five-long non-coding RNA signature to improve the prognosis prediction for patients with hepatocellular carcinoma
作者：Qiu-Jie Zhao;Jiao Zhang;Lin Xu;Fang-Feng Liu
作者机构：Department of Hepatobiliary Surgery,Shandong Provincial Hospital affiliated to Shandong University.;Department of Gastroenterology,Shandong Provin 更多
通讯作者地址：[Zhao, QJ]Shandong Univ, Shandong Prov Hosp, Dept Gastroenterol, 324,Jingwuwei 7th Rd, Jinan 250021, Shandong, Peoples R China.
关键词：Long non-coding RNA; Hepatocellular carcinoma; Prognosis; Survival; prediction; Prognostic biomarker
摘要：AIM To construct a long non-coding RNA(lnc RNA) signature for predicting hepatocellular carcinoma(HCC) prognosis with high efficiency.METHODS Differentially expressed lnc RNAs(DELs) between HCC specimens and peritumor liver specimens were identified using the edge R package to analyze The Cancer Genome Atlas(TCGA) LIHC dataset.Univariate Cox proportional hazards regression was performed to obtain the DELs significantly associated with overall survival(OS) in a training set.These OS-related DELs were further analyzed using a stepwise multivariate Cox regression model.Those lnc RNAs fitted in the multivariate Cox regression model and independently associated with overall survival were chosen to build a prognostic risk formula.The prognostic value ofthis formula was then validated in the test group and the entire cohort and further compared with two previously identified prognostic signatures for HCC.Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to explore the potential biological functions of the lnc RNAs in the signature.RESULTS Based on lnc RNA expression profiling of 370 HCC patients from the TCGA database,we constructed a 5-lnc RNA signature(AC015908.3,AC091057.3,TMCC1-AS1,DCST1-AS1 and FOXD2-AS1) that was significantly associated with prognosis.HCC patients with high-risk scores based on the expression of the 5 lnc RNAs had significantly shorter survival times compared to patients with low-risk scores in both the training and test groups.Multivariate Cox regression analysis demonstrated that the prognostic value of the 5 lnc RNAs was independent of clinicopathological parameters.A comparison study involving two previously identified prognostic signatures for HCC demonstrated that this 5-lnc RNA signature showed improved prognostic power compared with the other two signatures.Functional enrichment analysis indicated that the 5 lnc RNAs were potentially involved in metabolic processes,fibrinolysis and complement activation.CONCLUSION Our present study constructed a 5-l