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Identification of potential prognostic long non-coding RNA for predicting survival in intrahepatic cholangiocarcinoma.

ABSTRACT: Intrahepatic cholangiocarcinoma (ICC) is an aggressive biliary epithelial tumor with poor prognosis. There are increasing evidences that long non-coding RNAs (lncRNAs) are dysregulated in multifarious tumors, revealing potential significant role of lncRNAs in tumorigenesis.We used the ICC dataset retrieved from The Cancer Genome Atlas and the Gene Expression Omnibus database to obtain the lncRNAs expression profiles and identify potential prognostic lncRNAs for predicting the prognosis in ICC. Univariate and multivariate Cox regression analyses were performed to construct a prognostic index (PI). Furthermore, coexpression analysis and functional assessment were performed to initially investigate the function of these prognostic lncRNAs.A total of 255 differentially expressed lncRNAs (DElncRNAs) were identified among two RNA sequencing dataset of a total 63 ICC patients with 98 samples using R platform. Thirteen of 255 DElncRNAs were identified as prognostic lncRNAs and used for a PI. Patients with high PI were associated with poor prognostic (P = .0064), and the Cox regression showed consistent result (P?=?.042). The time-dependent receiver operating characteristic analysis showed the PI performed well in ICC survival prediction with an area under curve of 0.921, 0.801, and 0.717 for 1-, 3-, and 5-year survival, respectively.In conclusion, we included 13 identified prognostic DElncRNAs and constructed a prognostic signature/PI. ICC patient with higher PI was associated with poorer prognosis. However, the clinical role as well as biological functions of constructed PI and these prognostic DElncRNAs need to be verified in future study.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC7220432 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Identification of potential prognostic long non-coding RNA for predicting survival in intrahepatic cholangiocarcinoma.

Zhang Zeyu Z Wang Zhiming Z Huang Yun Y

Medicine 20200301 13

Intrahepatic cholangiocarcinoma (ICC) is an aggressive biliary epithelial tumor with poor prognosis. There are increasing evidences that long non-coding RNAs (lncRNAs) are dysregulated in multifarious tumors, revealing potential significant role of lncRNAs in tumorigenesis.We used the ICC dataset retrieved from The Cancer Genome Atlas and the Gene Expression Omnibus database to obtain the lncRNAs expression profiles and identify potential prognostic lncRNAs for predicting the prognosis in ICC. U ...[more]

PMID: 32221083

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Project description:Recent studies show that long non-coding RNAs (lncRNAs) play crucial roles in human cancers. However, functional lncRNAs and their downstream mechanisms are largely unknown in the molecular pathogenesis of intrahepatic cholangiocarcinoma (ICC) and its progression. In the present study, we performed transcriptomic profiling of five ICC and paired adjacent noncancerous tissues (N) using lncRNA and mRNA microarrays to identify relevant biomarkers in ICC. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the microarray results. We sought correlations between the expression levels of lncRNAs and those of target genes. Clinicopathological characteristics and overall survival were compared using the t-test and the Kaplan–Meier method, respectively. A total of 3,054 and 2,111 lncRNAs were significantly up- and down-regulated(fold change?2, p?0.05) in ICC tissues compared to the adjacent NT samples. Bioinformatic analysis indicated that most such genes were related to carcinogenesis, hepatic system disease, and signal transduction. Positive correlations were evident between four pairs of lncRNAs and target mRNAs (RNA43085 and SULF1, RNA47504 and KDM8, RNA58630 and PCSK6, and RNA40057 and CYP2D6). In addition, some lncRNAs and mRNAs were significantly associated with clinicopathological characteristics. The cumulative overall survival rate was significantly associated with low-level expression of CYP2D6 (p=0.005) and PCSK6 (p=0.038). And patients with high expression levels of CYP2D6 and RNA40057 have significant better prognosis (p=0.014). Our results suggested that lncRNA expression profile in ICC tissues is profoundly different from that in NT samples. The lncRNA signature could be used as a biomarker for the prognosis of patients with ICC. Furthermore, the combination of lncRNA and mRNA can reliably predict the survival. The lncRNA expression profiles of cancer and adjacent normal tissues form 5 ICC patients were studied by microarray and an combination of lncRNA and mRNA could be used as a biomarker for the prognosis of patients with ICC

Project description:BACKGROUND Accumulating evidence suggests the involvement of long non-coding RNAs (lncRNAs) as oncogenic or tumor suppressive regulators in the development of various cancers. In the present study, we aimed to identify a lncRNA signature based on RNA sequencing (RNA-seq) data to predict survival in esophageal cancer. MATERIAL AND METHODS The RNA-seq lncRNA expression data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed lncRNAs were screened out between esophageal cancer and normal tissues. Univariate and multivariate Cox regression analysis were performed to establish a lncRNA-related prognostic model. Receiver operating characteristic (ROC) analysis was conducted to test the sensitivity and specificity of the model. GO (gene ontology) functional and KEGG pathway enrichment analyses were performed for mRNAs co-expressed with the lncRNAs to explore the potential functions of the prognostic lncRNAs. RESULTS A total of 265 differentially expressed lncRNAs were identified between esophageal cancer and normal tissues. After univariate and multivariate Cox regression analysis, eight lncRNAs (GS1-600G8.5, LINC00365, CTD-2357A8.3, RP11-705O24.1, LINC01554, RP1-90J4.1, RP11-327J17.1, and LINC00176) were finally screened out to establish a predictive model by which patients could be classified into high-risk and low-risk groups with significantly different overall survival. Further analysis indicated independent prognostic capability of the 8-lncRNA signature from other clinicopathological factors. ROC curve analysis demonstrated good performance of the 8-lncRNA signature. Functional enrichment analysis showed that the prognostic lncRNAs were mainly associated with esophageal cancer related biological processes such as regulation of glucose metabolic process and amino acid and lipids metabolism. CONCLUSIONS Our study developed a novel candidate model providing additional and more powerful prognostic information beyond conventional clinicopathological factors for survival prediction of esophageal cancer patients. Moreover, it also brings us new insights into the molecular mechanisms underlying esophageal cancer.

Dataset Information

Identification of potential prognostic long non-coding RNA for predicting survival in intrahepatic cholangiocarcinoma.

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Identification of potential prognostic long non-coding RNA for predicting survival in intrahepatic cholangiocarcinoma.

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