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

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Jinlan Huang ◽  
Yansong Zheng ◽  
Xialin Xiao ◽  
Can Liu ◽  
Jinpiao Lin ◽  
...  

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.

2021 ◽  
Author(s):  
Yawei Han ◽  
Wenna Jiang ◽  
Yu Wang ◽  
Meng Zhao ◽  
Yueguo Li ◽  
...  

Abstract Background: Circulating long non-coding RNAs (lncRNAs) have been demonstrated to serve as diagnostic or prognosis biomarkers for various disease. We aimed to elucidate the diagnostic efficacy of serum lncRNA SCARNA10 for the hepatocellular carcinoma (HCC).Methods: In this study, a total of 127 patients with HCC, 55 patients with benign liver disease (BLD), and 99 healthy controls (HC) were enrolled in this study. According to different classifications, the levels of serum SCARNA10 were assessed by quantitative real-time polymerase chain reaction (qPCR). The correlations between serum SCARNA10 and clinicopathological charcaterisstics were further analyzed. The receiver operating characteristic (ROC) curve and area under curve (AUC) were utilized to estimate the diagnostic capacity of serum SCARNA10 and its combination with AFP for HCC. Results: The results demonstrated that the levels of serum SCARNA10 were significantly higher in HCC patients than in patients with BLD and healthy controls, and significantly increased in HCC patients with hepatitis B or C infection, or with liver cirrhosis. Furthermore, positive correlations were noted between serum SCARNA10 level and some clinicopathological characteristics, including tumor size, differentiation degrees, tumor stage, vascular invasion, tumor metastasis and complications. ROC analysis revealed that SCARNA10 had a significantly predictive value for HCC, the combination of SCARNA10 and AFP gained the higher accuracy. SCARNA10 retained significant diagnosis capabilities for AFP-negative HCC patients. Conclusions: In summary, lncRNA SCARNA10 may serve as a novel and non-invasive biomarker with relatively high sensitivity and specificity for HCC diagnosis.


2021 ◽  
Author(s):  
Yawei Han ◽  
Wenna Jiang ◽  
Yu Wang ◽  
Meng Zhao ◽  
Yueguo Li ◽  
...  

Abstract Circulating long non-coding RNAs (lncRNAs) have been demonstrated to serve as diagnostic or prognosis biomarkers for various disease. We aimed to elucidate the diagnostic efficacy of serum lncRNA SCARNA10 for the hepatocellular carcinoma (HCC). A total of 127 patients with HCC, 55 patients with benign liver disease (BLD), and 99 healthy controls (HC) were enrolled in this study. According to different classifications, the levels of serum SCARNA10 were assessed by quantitative real-time polymerase chain reaction (qPCR). The correlations between serum SCARNA10 and clinicopathological charcaterisstics were further analyzed. The receiver operating characteristic (ROC) curve and area under curve (AUC) were utilized to estimate the diagnostic capacity of serum SCARNA10 and its combination with AFP for HCC. The results demonstrated that the levels of serum SCARNA10 were significantly higher in HCC patients than in patients with BLD and healthy controls, and significantly increased in HCC patients with hepatitis B or C infection, or with liver cirrhosis. Furthermore, positive correlations were noted between serum SCARNA10 level and some clinicopathological characteristics, including tumor size, differentiation degrees, tumor stage, vascular invasion, tumor metastasis and complications. ROC analysis revealed that SCARNA10 had a significantly predictive value for HCC, the combination of SCARNA10 and AFP gained the higher accuracy. SCARNA10 retained significant diagnosis capabilities for AFP-negative HCC patients. In summary, lncRNA SCARNA10 may serve as a novel and non-invasive biomarker with relatively high sensitivity and specificity for HCC diagnosis.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yueting Han ◽  
Youqin Zhang ◽  
Lin Cui ◽  
Ze Li ◽  
Honglei Feng ◽  
...  

Abstract Purposes The purposes of this study were to assess the correlation between the plasma level of Hsp90α and the clinicopathological characteristics of patients with liver cancer and compare the diagnostic efficacy of Hsp90α, AFP, CEA, and CA199 in HCC. Experimental design A total of 200 individuals, including 140 patients with liver cancer or benign liver diseases and 60 healthy people, were enrolled for quantitative measurement of plasma Hsp90α by ELISA. Results The plasma level of Hsp90α was significantly different between patients with liver cancer or benign liver diseases and healthy controls (P < 0.001). The sensitivity, specificity, and AUC (95% CI) of Hsp90α were 93.2%, 85.4%, and 0.931% (0.891–0.972%), respectively, when Hsp90α was applied to differentiate liver cancer patients and healthy controls. Significant positive correlations between the plasma Hsp90α level and clinicopathological characteristics such as the history of basic liver disease (P = 0.038), active stage of hepatitis (P = 0.039), Child-Pugh score (P < 0.001), size of focal liver lesions (P = 0.004), and extrahepatic metastasis (P < 0.001) were observed. AFP + Hsp90α was the best combination strategy for the auxiliary diagnosis of HCC, with a sensitivity of 95.7%, a specificity of 97.5%, and an AUC of 0.990 (0.976–1.000). The level of plasma Hsp90α decreased significantly (P < 0.001) after resection of tumor tissue. Conclusions This study demonstrated that plasma Hsp90α levels are useful as a diagnostic biomarker in liver cancer and may predict the responses of patients with liver cancer to surgery. Some clinicopathological characteristics could affect the plasma Hsp90α levels.


2021 ◽  
Author(s):  
Zhuo Han ◽  
Keming Li ◽  
Jinyu Wu ◽  
Keyan Wang ◽  
Cuipeng Qiu ◽  
...  

Aim: The aim of this study was to evaluate the capacity of RNA in the diagnosis of hepatocellular carcinoma (HCC). Methods: A systematic review was conducted from PubMed, Cochrane Library, EMBASE and Web of Science databases via well-designed retrieval strategy. Subsequently, the network meta-analysis was performed by the STATA software. Results: Through statistical analysis, the three hypotheses of the network meta-analysis were established. In view of these hypotheses, the diagnostic efficacy of the three markers in HCC (HCC vs healthy people) may be consistent, and the cumulative ranking results showed such a trend: circular RNA >long noncoding RNA >microRNA. Conclusion: Circular RNA may be most effective for diagnosing HCC across the three types of RNA.


2017 ◽  
Vol 46 (1) ◽  
pp. 348-356 ◽  
Author(s):  
Zhi-kun Zheng ◽  
Cui Pang ◽  
Yang Yang ◽  
Qiong Duan ◽  
Ju Zhang ◽  
...  

Objective Long noncoding RNAs (lncRNAs) offer great potential as cancer biomarkers. This study was performed to assess the applicability of serum lncRNA urothelial carcinoma-associated 1 (UCA1) as a diagnostic and/or prognostic biomarker for hepatocellular carcinoma (HCC). Methods We examined UCA1 expression in serum samples from 105 patients with HCC, 105 patients with benign liver disease (BLD), and 105 healthy volunteers using reverse-transcription polymerase chain reaction and analyzed the relationship between serum UCA1 and clinicopathological parameters of HCC as well as survival. Results Expression of serum UCA1 was significantly higher in patients with HCC and allowed for discrimination of HCC from BLD and healthy controls. High expression of serum UCA1 was significantly associated with a high tumor grade, large tumor size, positive vascular invasion, and advanced TNM stage. Multivariate analysis revealed that a high serum UCA1 level was an independent unfavorable prognostic factor for HCC. Conclusions Our results confirm the upregulation of serum UCA1 expression in HCC and indicate its clinical value as a noninvasive biomarker for HCC screening and prognostic prediction.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gyeonghwa Kim ◽  
Ja Ryung Han ◽  
Soo Young Park ◽  
Won Young Tak ◽  
Young-Oh Kweon ◽  
...  

AbstractCircular RNAs (circRNAs) represent potential biomarkers because of their highly stable structure and robust expression pattern in clinical samples. The aim of this study was to evaluate the expression of a recently identified circRNA, hsa_circ_0005986; determine its clinical significance; and evaluate its potential as a biomarker of hepatocellular carcinoma (HCC). We evaluated hsa_circ_0005986 expression in 123 HCC tissue samples, its clinical significance, and its association with patients’ clinicopathological characteristics and survival. Hsa_circ_0005986 expression was downregulated in HCC tissues. Low hsa_circ_0005986 expression was more common in tumors larger than 5 cm [odds ratio (OR), 3.19; 95% confidence interval (CI), 1.51–6.76; p = 0.002], advanced TNM stage (III/IV; OR, 2.39; 95% CI, 1.16–4.95; p = 0.018), and higher BCLC stage (B/C; OR, 2.71; 95% CI, 1.30–5.65; p = 0.007). High hsa_circ_0005986 expression was associated with improved survival and was an independent prognostic factor for overall [hazard ratio (HR), 0.572; 95% CI, 0.339–0.966; p = 0.037] and progression-free (HR, 0.573; 95% CI, 0.362–0.906; p = 0.017) survival. Moreover, the circRNA–miRNA–mRNA network was constructed using RNA-seq/miRNA-seq data and clinical information from TCGA-LIHC dataset. Our findings indicate a promising role for hsa_circ_0005986 as a prognostic biomarker in patients with HCC.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Honglei Feng ◽  
Bole Li ◽  
Ze Li ◽  
Qian Wei ◽  
Li Ren

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the digestive system and has high morbidity and mortality rates. It is essential to search new biomarkers to improve the accuracy of early HCC diagnosis. Therefore, we evaluated the diagnostic value of prothrombin induced by vitamin K deficiency or antagonist- II (PIVKA-II) as a potential biomarker that complements α-fetoprotein (AFP) in HCC by detecting the serum PIVKA-II levels. Methods Serum PIVKA-II levels were compared in 168 HCC patients, 150 benign liver disease patients and 153 healthy controls to investigate the PIVKA-II potential to be a HCC biomarker. Receiver operating characteristic curve (ROC) analysis was used to evaluate the value of PIVKA-II in the diagnosis of HCC and its complementary role of AFP. The correlation between serum PIVKA-II levels and clinicopathological characteristics was analyzed to study the value of PIVKA-II in assessing HCC progression and prognosis. Finally, the ability of PIVKA-II in assessing the surgical treatment effects of HCC was studied by comparing the pre- and post-operative serum PIVKA-II levels in 89 HCC patients. Results Serum PIVKA-II levels in HCC patients were significantly higher than that in patients with benign liver disease and healthy controls. The PIVKA-II performance in the diagnosing HCC as an individual biomarker was remarkable. The combined detection of PIVKA-II and AFP improved the diagnostic efficiency of HCC. PIVKA-II retained significant diagnosis capabilities for AFP-negative HCC patients. Significant correlations were found between PIVKA-II expression levels and some clinicopathological characteristics, including tumor size, tumor stage, tumor metastasis, differentiation degree and complications. PIVKA-II expression obviously decreased after surgical resection. Conclusions PIVKA-II is a promising serum biomarker for the HCC diagnosis that can be used as a supplement for AFP. The combined diagnosis of the two markers greatly improved the diagnostic efficiency of HCC. The PIVKA-II levels in HCC patients were widely associated with clinicopathological characteristics representing tumor cell dissemination and/or poor prognosis. PIVKA-II can be used to evaluate the curative effects of HCC resection.


2020 ◽  
Vol 20 ◽  
Author(s):  
Nan Wang ◽  
Rui Kong ◽  
Wei Han ◽  
Jie Lu

Background: Hepatoid adenocarcinoma of the stomach (HAS) has been recognized as a rare primary gastric tumor characterized by hepatocellular carcinoma-like histology. HAS often causes diagnostic confusion with conventional gastric adenocarcinoma (CGA) due to the difficulty to detect hepatoid differentiation solely based on findings from hematoxylin and eosin (H&E) staining. Hence, HAS should be distinguished from solid-type CGA based on their different biological behaviors. β-catenin is highly expressed in hepatocellular carcinoma (HCC), which is involved in the maintenance of tumor initiating cells, drug resistance, tumor progression, and metastasis. Methods and Results: Given the dearth of HAS cases, systematic examination of the expression of β-catenin in HAS remains under-explored. In this study, 14 cases were subjected to immunostaining with with AFP, β-catenin, glypican3, hepar-1 and CerbB-2. In parallel, the clinicopathological characteristics of these patients were collected. We detected statistically significant difference in the expression of β-catenin (P = 0.000), glypican3 (P = 0.019), and hepar-1 (P = 0.007) between HAS cancer tissues and the adjacent non-cancerous tissues. Furthermore, a significant correlation was observed between the expression of β-catenin in HAS cancer tissue and adjacent tissue (Pearson correlation coefficient: 0.686, P = 0.007). Moreover, in cancer tissues, a significant correlation was observed between the expression of β-catenin and survival time (Spearman correlationcoefficient= - 0.482, P = 0.003). However, we found the expression of β-catenin did not correlate with the degree of tumor differentiation and tumor size, age, gender, serum AFP levels, microinvasion, and metastasis (P > 0.05). Conclusion: Our findings establish β-catenin as a useful marker that can distinguish HAS from CGA and may improve the early diagnosis to guide the appropriate and timely treatment of HAS patients.


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