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The long noncoding RNAs PVT1 and uc002mbe.2 in sera provide a new supplementary method for hepatocellular carcinoma diagnosis.

ABSTRACT: Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver in adults worldwide. Several studies have demonstrated that long noncoding RNAs (lncRNAs) are involved in the development of various types of cancer, including HCC. These findings prompted us to examine the detectability of lncRNAs in blood samples from patients with HCC. In this study, we explored the expression levels of 31 cancer-related lncRNAs in sera from 71 HCC patients and 64 healthy individuals by reverse transcription and quantitative polymerase chain reaction (RT-qPCR). We found that 25 lncRNAs could be detected in the serum and that 7 had significantly different expression levels. A 2-lncRNA signature (PVT1 and uc002mbe.2) identified by stepwise regression showed potential as a diagnostic marker for HCC. The area under the receiver operating characteristic (ROC) curve was 0.764 (95% CI: 0.684-0.833). The sensitivity and specificity values of this serum 2-lncRNA signature for distinguishing HCC patients from the healthy group were 60.56% and 90.62%, respectively. The diagnostic ability of the combination of the serum 2-lncRNA signature with alpha-fetoprotein (AFP) was much greater than that of AFP alone. The expression levels of the 2 lncRNAs were associated with clinical parameters including tumor size, Barcelona Clinic Liver Cancer (BCLC) stage, and serum bilirubin.

SUBMITTER: Yu J

PROVIDER: S-EPMC4979822 | biostudies-other | 2016 Aug

REPOSITORIES: biostudies-other

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The long noncoding RNAs PVT1 and uc002mbe.2 in sera provide a new supplementary method for hepatocellular carcinoma diagnosis.

Yu Jinyu J Han Junqing J Zhang Jian J Li Guanzhen G Liu Hui H Cui Xianping X Xu Yantian Y Li Tao T Liu Juan J Wang Chuanxi C

Medicine 20160801 31

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver in adults worldwide. Several studies have demonstrated that long noncoding RNAs (lncRNAs) are involved in the development of various types of cancer, including HCC. These findings prompted us to examine the detectability of lncRNAs in blood samples from patients with HCC. In this study, we explored the expression levels of 31 cancer-related lncRNAs in sera from 71 HCC patients and 64 healthy individuals by reverse ...[more]

PMID: 27495068

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Project description:BackgroundAll cell types express long non-coding RNAs (lncRNAs), which have the potential to play a role in carcinogenesis by altering the levels of their expression. Squamous cell carcinoma of the esophagus (ESCC) is a deadly disease with a poor prognosis and a high frequency of lymphatic metastases. Understanding the functional role and signaling pathways of two neighboring lncRNAs, CCAT1 and PVT1, in this oncogene's pathogenesis may help us determine ESCC. Furthermore, it is still unclear whether these lncRNAs are linked to the clinicopathological characteristics of patients with ESCC.MethodsFor this study, we used biopsy from the Imam Khomeini Cancer Institute's tumor bank in Tehran, Iran to obtain 40 ESCC tumor samples and their normal margin counterparts. The expression levels of the CCAT1, PVT1, and c-MYC genes were assessed using quantitative Real-Time RT-PCR. Additionally, demographic data and clinical-pathologic characteristics, such as tumor grade, tumor stage, lymph node, and metastasis, were taken into consideration. Graphpad prism version 8 was used for bioinformatics analyses.ResultsComparing ESCC tissues to non-tumor tissues, we found significant upregulation of PVT1, CCAT1, and c-MYC. Patients with ESCC who had increased PVT1 expression also had higher rates of advanced stage and lymph node metastasis, whereas increased CCAT1 expression was only linked to advanced stage and wasn't associated with lymph node metastasis. In predicting ESCC, CCAT1 (p < 0.05) was found to be an important factor. Overall survival was reduced by c-MYC and PVT1 overexpression (p < 0.001), according to Kaplan-Meier analysis. PVT1, CCAT1, and c-MYC were found to interact with 23 miRNAs with high and medium score classes, as shown in a bioinformatics study. We summarized the experimentally proven interactions between c-MYC, PVT1, and CCAT1 and other miRNAs, lncRNAs, and proteins.ConclusionThis is the first report that CCAT1, PVT1 and c-MYC have been found to be up-regulated simultaneously in ESCC. It is possible that these genes may be involved in ESCC as a result of these findings. Therefore, as consequence, more research is needed to determine whether or not these lncRNAs play an oncogenic role in ESCC development and progression, as well as the regulatory mechanisms that control them.

Dataset Information

The long noncoding RNAs PVT1 and uc002mbe.2 in sera provide a new supplementary method for hepatocellular carcinoma diagnosis.

Publications

The long noncoding RNAs PVT1 and uc002mbe.2 in sera provide a new supplementary method for hepatocellular carcinoma diagnosis.

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