Background & Aims: Current studies have indicated that long non-coding RNAs (lncRNAs) could act as tumor biomarkers for disease diagnosis and prognosis prediction. In this study, we mainly focused on determining the expression of circulating lncRNAs in patients suffering for hilar cholangiocarcinoma (HC), aiming to reveal the potential lncRNA as a fingerprint. Methods: A total 12 lncRNAs were previously proven to be aberrantly expressed in HC tumor tissues. All of the 12 lncRNAs were selected as candidate targets for subsequent circulating lncRNA assay. The candidate lncRNAs were validated by qRT-PCR arranged in training and validation sets. The risk score analysis was employed. Data was presented with receiver operating characteristic curve (ROC). Results: Circulating PCAT1, MALAT1, and CPS1-IT1 were significantly increased in plasma samples of HC patients in both the training set and validation set. Through ROC analysis, we found that the three plasmatic lncRNAs presented the area under ROC curve value (AUC) as 0.784, 0.860, and 0.677. Further combination with the three factors indicated a higher power (AUC, 0.893; sensitivity, 85.5%; specificity, 93.2%). Conclusion: This was the first time to reveal the potential circulating fingerprints for predicting HC. PCAT1, MALAT1, and CPS1-IT1 may act as novel early diagnosis biomarkers for predicting HC.

Purpose: It has been reported that miRNA-124 inhibits hepatocellular carcinoma (HCC) progression, while lncRNA-UCA1 promotes HCC. The aim of this study is to find whether miRNA-124, as a tumor suppressor in HCC can inhibit lncRNA-UCA1 in HCC cell. Methods: Tumor tissues and adjacent healthy tissues were obtained from 66 patients diagnosed with HCC in Binzhou Medical University Hospital from January 2011 to January 2013. Cell proliferation assay, in vitro cell migration and invasion assay were applied for the research. Results: In the present study we found that miRNA-124 was downregulated, while lncRNA-UCA1 was upregulated in tumor tissues comparing to adjacent healthy tissues of HCC patients. Expression of miRNA-124 and lncRNA-UCA1 in tumor tissues were not affected by HBV or HCV infection. Analysis of followed-up data revealed that low miRNA-124 level and high lncRNA-UCA1 level were closely correlated with poor survival. Overexpression of miRNA-124 led to inhibited lncRNA-UCA1 expression in cells of HCC cell lines, while overexpression of lncRNA-UCA1 failed to significantly affect miRNA-124 expression. Expression levels of miRNA-124 and lncRNA-UCA1 were inversely and significantly correlated in tumor tissues but not in adjacent healthy tissues. Overexpression of miRNA-124 led to inhibited, while overexpression of lncRNA-UCA1 led to increased proliferation, migration and invasion rates of HCC cell lines. In addition, lncRNA-UCA1 overexpression attenuated the inhibitory effects of miRNA-124 overexpression on cancer cell proliferation, migration and invasion. Conclusion: Therefore, miRNA-124 may inhibit the proliferation, migration and invasion of cancer cell in hepatocellular carcinoma by downregulating lncRNA-UCA1.

In this study genotyping of hepatocellular carcinoma (HCC) patients was conducted to detect polymorphisms on the X-ray repair cross-complementing 1 (XRCC1) and xeroderma pigmentosum complementary group D (XPD) genes and analyze the relationship of their presence with the clinical features of the cancer. A total of 172 patients with HCC were selected in Qilu Hospital, Shandong University, from January 2010 to September 2011. All patients underwent resection of HCC and no tumor metastases were found. Peripheral venous blood samples (3–5 ml) were collected from the patients to extract genomic DNA. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and gene sequencing. During the five-year follow-up, the survival of patients with various genotypes of XRCC1 and XPD genes were observed and compared. Logistic regression analysis was used to analyze the association between single nucleotide polymorphisms of XRCC1 and XPD genes and the prognosis of patients with HCC. χ2 tests showed that XRCC1-194, XRCC1-280 and XPD-312 gene polymorphisms were significantly correlated with the number, location and diameter of the tumors (p<0.05). No significant difference was found in the survival curve of patients presenting different genotypes of the XRCC1-194 locus (p>0.05). Nevertheless, a significant difference was found in the survival curve of patients with AA and GG genotypes of the XRCC1-280 locus and in the patients with AA, GA and GG genotypes of the XPD-312 locus (p<0.05). Logistic regression analysis showed that the XRCC1-194 genotype was not an independent risk factor for HCC mortality risk (p>0.05), but XRCC1-280 (OR=1.815, p<0.01) and XPD-312 (OR=1.815, p<0.01) genotypes were independent risk factors for a poor prognosis. Taken together our results point to polymorphisms in XRCC1 and XPD genes as being related to the clinical characteristics of HCC, making them suitable prognostic markers of HCC.