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

Abstract

Background. 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). Methods. 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. Results. 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. Conclusion. The panel of serum Linc00152, UCA1, and AFP demonstrates a novel and noninvasive biomarker with relatively high sensitivity and specificity for HCC diagnosis.

Circulating Long and Circular Noncoding RNA as Non-Invasive Diagnostic Tools of Hepatocellular Carcinoma

“…Further research showed that circulating HULC in HCC patients could be used as a diagnostic marker, being highly up-regulated in patients with HCC compared to healthy individuals [ 39 , 40 , 41 ], with the area under the curve (AUC) of the receiver operator characteristic (ROC) curve around 0.80. Several studies; however, did not find up-regulation of HULC in HCC samples set [ 16 , 42 ].…”

“…It was hypomethylated in tumor tissues and human HCC cell lines [ 68 ] and during hepatocarcinogenesis [ 69 ]. In the blood, the expression level of LINC00152 increased from normal healthy control to chronic hepatitis B, liver cirrhosis, being highest in HCC [ 41 , 42 ]. Among other lncRNAs including HULC, LINC00152 was found to be the best diagnostic lncRNA with high AUC and sensitivity/specificity values [ 41 ].…”

“…In the blood, the expression level of LINC00152 increased from normal healthy control to chronic hepatitis B, liver cirrhosis, being highest in HCC [ 41 , 42 ]. Among other lncRNAs including HULC, LINC00152 was found to be the best diagnostic lncRNA with high AUC and sensitivity/specificity values [ 41 ]. Plasma and exosomal LINC00152 were also significantly elevated in gastric cancer patients compared with healthy controls, indicating its use in the cancer diagnosis [ 70 ].…”

“…A meta-analysis of seven studies validated the result, showing the association of UCA1 expression with tumor size, metastasis, and overall survival [ 78 ]. Several studies demonstrated the high expression of UCA1 in sera samples of HCC patients [ 41 , 47 , 48 , 49 ]. These studies showed a good AUC value > 0.800.…”

“…A recent 2020 study showed that serum MALAT1 expression could distinguish HCC from healthy individuals and chronic hepatitis with AUC 0.768 and 0.733, respectively. However, these values were lower compared to HULC and LINC00152 [ 41 ].…”