The clinical significance of long non-coding RNAs MALAT1 and CASC2 in the diagnosis of HCV-related hepatocellular carcinoma.

Globally, hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death due to a lack of early predictive and/or diagnostic tools. Thus, research for a new biomarker is important. LncRNAs play a functional role in target gene regulation and their deregulation is associated with several pathological conditions including HCC. This study aimed to explore the diagnostic potential of two LncRNAs MALAT1 and CASC2 in HCC compared to the routinely used diagnostic biomarker. The current study is a case-control study carried out at Fayoum University Hospital and conducted on 89 individuals. The study included three groups of 36 HCC patients on top of HCV(HCC/HCV), 33 HCV patients, and 20 healthy volunteers as a control group. All study subjects were subjected to radiological examinations. The determination of CBC was performed by the automated counter and liver function tests by the enzymatic method were performed. In addition, HCV RNA quantification and the expression level of two LncRNAs (MALAT1 and CASC2) were performed by qRT-PCR. The results revealed a statistically significant difference between study groups regarding liver function tests with a higher mean in HCC/HCV group. Also, serum MALAT1 significantly up-regulated in HCV (11.2±2.8) and HCC/HCV (4.56±1.4) compared to the control group. Besides, serum CASC2 levels in the HCV group were significantly upregulated (14.9±3.6), while, downregulated in the HCC group (0.16± 0.03). Furthermore, The ROC analysis for diagnostic efficacy parameters indicated that CASC2 has higher accuracy (94.6%) and sensitivity (97.2%) for HCC diagnosis than AFP with an accuracy of (90.9%), sensitivity (69.4%), and MALAT1 showed an accuracy of (56.9%), sensitivity (72.2%). Our study results indicated that CASC2 is a promising biomarker and is considered better and could help in HCC diagnosis on top of HCV than MALAT1 and the routine biomarker AFP.

Golam RM ，Khalil MAF ，Shaker OG ，Ahmed TI ，Elguaad MKA ，Hassan EA ，El-Ansary MRM ，Ismail A ，Kandil YI ，Mohammed OA ，Doghish AS ... -  《PLoS One》

Long non-coding RNAs (CASC2 and TUG1) in hepatocellular carcinoma: Clinical significance.

The biology of hepatocellular carcinoma remains poorly understood. Long non-coding RNAs (lncRNAs) have been confirmed to be key regulators of most cell processes and cancer. The lncRNA cancer susceptibility candidate 2 (CASC2) was originally identified as a downregulated gene in endometrial cancer and acted as a tumor suppressor. The lncRNA taurine up-regulated gene 1 (TUG1) has been shown to play an oncogenic role in various cancers. However, the relative expression of CASC2 and TUG1 in hepatocellular carcinoma (HCC) on top of hepatitis C virus (HCV) and the relationship between both remains unclear. The present study aimed to evaluate both lncRNA CASC2 and TUG1 relative gene expression in whole blood of HCC/HCV patients in relation to HCV and healthy subjects and to relate them to each other and to different clinicopathological factors. The relative expression of CASC2 and TUG1 was estimated by a quantitative reverse transcriptase-polymerase chain reaction in 30 HCC/HCV patients and compared with 20 cases of HCV patients and 20 controls. CASC2 was downregulated in HCC/HCV patients, whereas TUG1 was overexpressed in relation to HCV and the control group, indicating their antagonistic effect. This suggests their role in the pathogenesis of HCC on top of HCV. Their expression was correlated to Barcelona Clinic Liver Cancer stage and serum alpha-fetoprotein level. CASC2 and TUG1 could be new potential biomarkers with a valid non-invasive technique.

Refai NS ，Louka ML ，Halim HY ，Montasser I ... -  《-》

Long Noncoding RNAs MALAT1 and HOTTIP Act as Serum Biomarkers for Hepatocellular Carcinoma.

Bao H ，Jiang Y ，Wang N ，Su H ，Han X ... -  《-》

A Circulating Long Noncoding RNA Panel Serves as a Diagnostic Marker for Hepatocellular Carcinoma.

Circulating long noncoding RNAs (lncRNAs) have been demonstrated to serve as diagnostic biomarkers for various cancers. We aimed to elucidate the diagnostic efficacy of eight serum lncRNAs HULC, MALAT1, Linc00152, PTENP1, PTTG3P, SPRY4-IT1, UBE2CP3, and UCA1 and their combinations for the diagnosis of hepatocellular carcinoma (HCC). A total of 129 patients with HCC, 49 patients with liver cirrhosis, 27 patients with chronic hepatitis B, and 93 healthy controls were enrolled in this study. The levels of serum lncRNAs were assessed by quantitative real-time polymerase chain reaction. The correlations between serum lncRNAs and clinicopathological characteristics were further analyzed. The receiver operating characteristic (ROC) curve and area under curve (AUC) were utilized to estimate the diagnostic capacity of serum lncRNAs and their combination with AFP for HCC. A logistic regression model was performed to establish a multiple-lncRNA panel. The levels of serum HULC, MALAT1, Linc00152, PTTG3P, SPRY4-IT1, UBE2CP3, and UCA1 were significantly higher in HCC patients than in patients with benign liver diseases and healthy controls, whereas serum PTENP1 was significantly decreased in HCC patients compared with healthy participants. Positive correlations between serum Linc00152 and GGT, serum PTTG3P and GGT, and serum SPRY4-IT1 and ALT were noted in HCC patients. ROC analysis revealed that all these lncRNAs had a significantly predictive value for HCC except for PTENP1. The best performance of single lncRNA was obtained by Linc00152 with an AUC of 0.877. When combined with AFP, the combination of Linc00152 and AFP gained the highest accuracy, yielding an AUC of 0.906. Through logistic regression analysis, the panel consisting of serum linc00152, UCA1, and AFP provided the greatest predictive ability, obtaining an AUC of 0.912 with 82.9% sensitivity and 88.2% specificity. The panel of serum Linc00152, UCA1, and AFP demonstrates a novel and noninvasive biomarker with relatively high sensitivity and specificity for HCC diagnosis.

Huang J ，Zheng Y ，Xiao X ，Liu C ，Lin J ，Zheng S ，Yang B ，Ou Q ... -  《-》

Oncogenic long noncoding RNA MALAT1 and HCV-related hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. The oncogenic function of the long non-coding RNA; metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in HCC remains unclear. We aimed to evaluate MALAT1 serum expression profile in HCC and explore its relation to the clinicopathological features. Quantitative Real Time-Polymerase Chain Reaction was applied in 70 cohorts (30 HCC, 20 HCV, 20 controls). Further meta-analysis of clinical studies and in vitro validated experiments was employed. Serum MALAT1 showed area under the curve of 0.79 and 0.70 to distinguish patients with cancer from normal and cirrhotic individuals at fold change of 1.0 and 1.26, respectively. Expression level was significantly higher in males (P <0.001) and patients with massive ascites (P = 0.005). Correlation analysis showed positive correlation of MALAT1 with total bilirubin (r = 0.456, P <0.001) and AST (r = 0.280, P = 0.019), and negative correlation with the hemoglobin level (r = 0.312, P = 0.009). Meta-analysis showed that the over-expressed MALAT1 was linked to tumor number [Cohen's d = 0.450, 95% CI (0.21 to 0.68)], clinical stage [Cohen's d = 0.048, 95% CI (-0.83 to 0.74)], and AFP level [Cohen's d = 0.354, 95% CI (0.1 to 0.57)]. In silico data analysis and systematic review confirmed MALAT1 oncogenic function in cancer development and progression. In conclusion, circulatory MALAT1 might represent a putative non-invasive prognostic biomarker indicating worse liver failure score in HCV-related HCC patients with traditional markers. Large-scale verification is warranted in future studies.

Toraih EA ，Ellawindy A ，Fala SY ，Al Ageeli E ，Gouda NS ，Fawzy MS ，Hosny S ... -  《-》