HULC and Linc00152 Act as Novel Biomarkers in Predicting Diagnosis of Hepatocellular Carcinoma

Background/Aims: The alterations of long non-coding RNAs (lncRNAs) are related to multiple diseases. They can be detected in plasma as biomarkers for the diagnosis of multiple diseases. In this study, we aimed to determine the expression of circulating lncRNAs in human, which may be promising biomarkers for the diagnosis of hepatocellular carcinoma (HCC). Methods: Eight lncRNAs were chosen as candidates on the basis of the literature to evaluate the diagnostic value and accuracy of the plasma lncRNA profiling system. The candidate lncRNAs were validated by qRT-PCR arranged in the training and validation sets. Additional double-blind testing was performed in 20 patients clinically suspected of having HCC. Results: Circulating HULC and Linc00152 were significantly up-regulated in plasma samples of HCC patients during training set and validation set. Areas under the receiver operating characteristic (ROC) curves of the validated two lncRNAs signature were 0.78 and 0.85, respectively. Combination of HULC and Linc00152 possessed a moderate ability to discrimination between HCC and control with an area under ROC value of 0.87 while the combination of AFP was 0.89 with a positive correlation with tissues expression. Conclusions: Our results suggest that both plasma levels of HULC and Linc00152 achieve a fine diagnostic accuracy in diagnosing ontogenesis and metastasis of HCC and may act as novel biomarkers for HCC.

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Tumor-Derived Exosomal Long Noncoding RNAs as Promising Diagnostic Biomarkers for Prostate Cancer

Cellular Physiology and Biochemistry ◽

10.1159/000488620 ◽

2018 ◽

Vol 46 (2) ◽

pp. 532-545 ◽

Cited By ~ 30

Author(s):

Yu-Hui Wang ◽

Jia Ji ◽

Bi-Cheng Wang ◽

Hao Chen ◽

Zhong-Hua Yang ◽

...

Keyword(s):

Prostate Cancer ◽

Tumor Invasion ◽

Operating Characteristic ◽

Specific Antigen ◽

Roc Curves ◽

Diagnostic Value ◽

Healthy Individuals ◽

Diagnostic Biomarkers ◽

Non Invasive ◽

Non Coding Rnas

Background/Aims: Exosomal circulating long non-coding RNAs (lncRNAs) in blood are emerging as clinically useful and non-invasive biomarkers for tumor diagnosis. However, normal cells can also secrete exosomes, so it is a prerequisite to obtain tumor-derived exosomes for better understanding of their diagnostic impacts in cancer. In this study, a dual-antibody-functionalized immunoaffinity system was established to isolate exosomes and investigate their lncRNAs expression pattern and clinical significance in prostate cancer (PCa). Methods: A commercially available kit was used to isolate total exosomes, which were then purified by a dual-antibody-functionalized immunoaffinity system. RT-qPCR was performed to detect the expression of exosomal lncRNAs. Receiver operating characteristic (ROC) curves were plotted to assess the diagnostic value. Results: Expression levels of two lncRNAs in tumor-derived exosomes were significantly higher than those in total exosomes. The levels of SAP30L-AS1 were upregulated in benign prostatic hyperplasia (BPH), and SChLAP1 levels were significantly higher in PCa than in BPH and healthy individuals. The area under the ROC curve indicated that SAP30L-AS1 and SChLAP1 had adequate diagnostic value to distinguish PCa from controls. Two lncRNAs separately combined with prostate specific antigen (PSA) possessed a moderate ability for discrimination. SAP30L-AS1 expression level was related to PSA values and tumor invasion. SChLAP1 expression was significantly higher in patients with higher Gleason scores, and was also effective in differentiating between BPH and PCa when the concentration of PSA was in the gray zone. Conclusion: The isolation of tumor-derived exosomes by dual-antibody-functionalized immunoaffinity systems and detection of their lncRNAs in plasma may lead to the identification of suitable biomarkers, with potential diagnostic utility.

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Evaluation of alpha-l-fucosidase for the diagnosis of hepatocellular carcinoma based on meta-analysis

LaboratoriumsMedizin ◽

10.1515/labmed-2019-0152 ◽

2020 ◽

Vol 0 (0) ◽

Cited By ~ 1

Author(s):

Lei Xi ◽

Chunqing Yang

Keyword(s):

Hepatocellular Carcinoma ◽

Operating Characteristic ◽

Meta Analysis ◽

Area Under The Curve ◽

Diagnostic Odds Ratio ◽

Diagnostic Value ◽

Receiver Operating Characteristic Curves ◽

Sensitivity Specificity ◽

Review Manager

AbstractObjectivesThe main aim of the present study was to assess the diagnostic value of alpha-l-fucosidase (AFU) for hepatocellular carcinoma (HCC).MethodsStudies that explored the diagnostic value of AFU in HCC were searched in EMBASE, SCI, and PUBMED. The sensitivity, specificity, and DOR about the accuracy of serum AFU in the diagnosis of HCC were pooled. The methodological quality of each article was evaluated with QUADAS-2 (quality assessment for studies of diagnostic accuracy 2). Receiver operating characteristic curves (ROC) analysis was performed. Statistical analysis was conducted by using Review Manager 5 and Open Meta-analyst.ResultsEighteen studies were selected in this study. The pooled estimates for AFU vs. α-fetoprotein (AFP) in the diagnosis of HCC in 18 studies were as follows: sensitivity of 0.7352 (0.6827, 0.7818) vs. 0.7501 (0.6725, 0.8144), and specificity of 0.7681 (0.6946, 0.8283) vs. 0.8208 (0.7586, 0.8697), diagnostic odds ratio (DOR) of 7.974(5.302, 11.993) vs. 13.401 (8.359, 21.483), area under the curve (AUC) of 0.7968 vs. 0.8451, respectively.ConclusionsAFU is comparable to AFP for the diagnosis of HCC.

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Serum Exosomal MicroRNAs as Potential Circulating Biomarkers for Endometriosis

Disease Markers ◽

10.1155/2020/2456340 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10 ◽

Cited By ~ 6

Author(s):

Lu Zhang ◽

Huihui Li ◽

Ming Yuan ◽

Dong Li ◽

Chang Sun ◽

...

Keyword(s):

Area Under The Curve ◽

Roc Curves ◽

Diagnostic Value ◽

Pcr Analysis ◽

Go Annotation ◽

Qrt Pcr ◽

Noninvasive Biomarker ◽

Novel Biomarkers ◽

Negative Controls ◽

Exosomal Mirna

Background. A reliable noninvasive biomarker is not yet available for endometriosis diagnosis. Novel biomarkers for the diagnosis of endometriosis are urgently needed. The molecular constituents of exosomes, especially exosomal microRNAs (miRNAs), have considerable potential as novel biomarkers for clinical diagnosis. This study is aimed at exploring aberrant exosomal miRNA profiles by using miRNA microarray and at providing more accurate molecular biomarkers of endometriosis. Methods. Exosomes were isolated from the serum of patients with endometriosis and negative controls and identified by electron microscopy, nanoparticle tracking analysis, and Western blot. Exosomal miRNAs were profiled by miRNA microarrays. The expression of selective serum exosomal miRNA was validated by qRT-PCR. Receiver operating characteristic (ROC) curves were established to explore the diagnostic value of selective miRNAs. Finally, GO annotation and KEGG pathway enrichment analyses were used to display possible functions associated with the two miRNAs. Results. A total of 24 miRNAs showed differential levels of enrichment with P<0.05 and log2 fold change>1 by miRNA microarrays. Among the six selective miRNAs (i.e., miR-134-5p, miR-197-5p, miR-22-3p, miR-320a, miR-494-3p, and miR-939-5p), qRT-PCR analysis revealed that miR-22-3p and miR-320a were significantly upregulated in serum exosomes from patients with endometriosis compared with negative individuals. ROC curve revealed that the serum exosomal miR-22-3p and miR-320a yielded the area under the curve values of 0.855 and 0.827, respectively. Conclusion. Our results demonstrated that exosomal miR-22-3p and miR-320a were significantly increased in the sera of patients with endometriosis. The two miRNAs may be useful potential biomarkers for endometriosis diagnosis.

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Ganji Formulation for Patients with Hepatocellular Carcinoma Who Have Undergone Surgery: A Multicenter, Randomized, Double-Blind, Controlled Trial

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/9492034 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6

Author(s):

Jing-Hao Zhang ◽

Chao Zheng ◽

Xiao-Jun Zhu ◽

Xin Zhang ◽

Zhi-Jun Hou ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Treatment Group ◽

Liver Resection ◽

Controlled Trial ◽

Disease Free Survival ◽

Control Group ◽

Double Blind ◽

Local Ablation ◽

Significant Difference ◽

And Control

Objective. To ascertain the efficacy and safety of Ganji Formulation (GF) for patients with Hepatocellular carcinoma (HCC) who had undergone surgery. Materials and Methods. A total of 262 HCC patients who had undergone liver resection, local ablation, or transcatheter arterial chemoembolization (TACE) were divided randomly into the treatment group and control group. The former was treated with GF and the later with placebo, both for 6 months. The primary endpoint was overall survival (OS). Second endpoints were disease-free survival (DFS) or time to disease progression (TTP). Results. OS of the treatment group was significantly longer than that of the control group (P < 0.05). Subgroup analysis showed that, for patients who received TACE, the TTP was significantly longer in the treatment group than in the control group (P < 0.05). However, for patients who underwent liver resection or local ablation, there was no significant difference in DFS between the two groups (P > 0.05). Conclusion. GF could improve postoperative cumulative survival and prolong the TTP. This clinical trial number is registered with ChiCTR-IOR-15007349.

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Improving the Detection of Hepatocellular Carcinoma using serum AFP expression in combination with GPC3 and micro-RNA miR-122 expression

Open Life Sciences ◽

10.1515/biol-2019-0007 ◽

2019 ◽

Vol 14 (1) ◽

pp. 53-61 ◽

Cited By ~ 1

Author(s):

Jian Li ◽

Sun Qiyu ◽

Tiezheng Wang ◽

Boxun Jin ◽

Ning Li

Keyword(s):

Hepatocellular Carcinoma ◽

Operating Characteristic ◽

Early Stage ◽

Roc Curves ◽

Micro Rna ◽

Serum Samples ◽

Serum Alpha Fetoprotein ◽

Laboratory Investigations ◽

Chronic Hcv ◽

Positive Controls

AbstractEarly diagnosis of hepatocellular carcinoma (HCC) greatly improves the survival and prognosisfor patients. In this study weevaluate the diagnostic promise of combining serum alpha-fetoprotein (AFP) expression with two potential biomarkers, serum glypican-3 (GPC3) and expression of the micro-RNA miR-122 for hepatitis C virus (HCV) related early-stage HCC. For this study serum samples from 47 patients with early-stage HCC, 54 chronic HCV (CH) carriers, 35 patients with liver cirrhosis (LC) and 54 health controls (HC) were collected. In addition to routine laboratory investigations, serum AFP, GPC3 and miR-122 were measured in all patients and healthy controls. Receiver operating characteristic (ROC) curves were used to present sensitivity and specificity for the biomarkers. The three markers were all significantly elevated in the serum samples from HCC patients. ROC curves showed the three markers had similar diagnostic capacities for distinguishing early-stage HCC from HCV-positive controls (LC + CH). In order to distinguish early-stage HCC from high-risk LC patients, the expression of miR-122 was superior to GPC3. Combination of the three markers as a panel showed a better diagnostic performance than any of the single markers (P <0.05). Overall, this study revealed that serum expression of GPC3 and miR-122 may be useful biomarkers to combine with serum AFP expression for the diagnosis of HCV related early-stage HCC.

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Use of Ultrasmall Superparamagnetic Iron Oxide Enhanced Susceptibility Weighted Imaging and Mean Vessel Density Imaging to Monitor Antiangiogenic Effects of Sorafenib on Experimental Hepatocellular Carcinoma

Contrast Media & Molecular Imaging ◽

10.1155/2017/9265098 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Shuohui Yang ◽

Jiang Lin ◽

Fang Lu ◽

Zhihong Han ◽

Caixia Fu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Iron Oxide ◽

Superparamagnetic Iron Oxide ◽

Treated Group ◽

Vessel Density ◽

Susceptibility Weighted Imaging ◽

Sorafenib Treatment ◽

Ultrasmall Superparamagnetic Iron Oxide ◽

Novel Biomarkers ◽

And Control

We investigated effectiveness of ultrasmall superparamagnetic iron oxide enhanced susceptibility weighted imaging (USPIO-enhanced SWI) and mean vessel density imaging (Q) in monitoring antiangiogenic effects of Sorafenib on orthotopic hepatocellular carcinoma (HCC). Thirty-five HCC xenografts were established. USPIO-enhanced SWI and Q were performed on a 1.5 T MR scanner at baseline, 7, 14, and 21 days after Sorafenib treatment. Intratumoral susceptibility signal intensity (ITSS) and Q were serially measured and compared between the treated (n = 15) and control groups (n = 15). Both ITSS and Q were significantly lower in the treated group at each time point (P < 0.05). Measurements in the treated group showed that ITSS persisted at 7 days (P = 0.669) and increased at 14 and 21 days (P < 0.05), while Q significantly declined at 7 days (P = 0.028) and gradually increased at 14 and 21 days. In the treated group, significant correlation was found between Q and histologic microvessel density (MVD) (r = 0.753, P < 0.001), and ITSS correlated well with MVD (r = 0.742, P = 0.002) after excluding the data from baseline. This study demonstrated that USPIO-enhanced SWI and Q could provide novel biomarkers for evaluating antiangiogenic effects of Sorafenib on HCC.

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Circulating expression of Hsa_circRNA_102893 contributes to early gestational diabetes mellitus detection

Scientific Reports ◽

10.1038/s41598-020-76013-5 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Hongling Yang ◽

Weitao Ye ◽

Ruihua Chen ◽

Fangling Zeng ◽

Yan Long ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Early Pregnancy ◽

Roc Curves ◽

Diagnostic Value ◽

Circular Rnas ◽

Qrt Pcr ◽

Noninvasive Biomarker ◽

Novel Biomarkers

Abstract Due to a poor availability of reliable biomarkers, detecting gestational diabetes mellitus (GDM) in early pregnancy remains a challenge. Novel biomarkers like Circular RNAs (circRNAs) may be a promising diagnostic tool. The aim of this study was (a) to identify circRNAs deregulated in GDM and (b) evaluate the potential of circRNAs in detecting GDM. The circRNAs expression profiling in 6 paired women (with and without GDM) was measured by microarray. The levels of five most relevant circRNAs were validated in 12 paired participants by qRT-PCR. To verify the reproducibility of qRT-PCR, significantly differential expressed circRNA levels were confirmed in 18 paired participants. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value. The areas under ROC curves of hsa_circRNA_102893 were 0.806 (95% CI 0.594–0.937) and 0.741 (0.568–0.872) in training set and test set, respectively. Circulating circRNAs reflect the presence of GDM. Hsa_circRNA_102893 may be a potential novel and stable noninvasive biomarker for detecting GDM in early pregnancy.

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Inflammatory Breast Carcinoma: Elevated microRNA miR-181b-5p and Reduced miR-200b-3p, miR-200c-3p, and miR-203a-3p Expression as Potential Biomarkers with Diagnostic Value

Biomolecules ◽

10.3390/biom10071059 ◽

2020 ◽

Vol 10 (7) ◽

pp. 1059

Author(s):

Sarah Atef Fahim ◽

Mahmoud Salah Abdullah ◽

Nancy A. Espinoza-Sánchez ◽

Hebatallah Hassan ◽

Ayman M. Ibrahim ◽

...

Keyword(s):

Breast Cancer ◽

Diagnostic Accuracy ◽

Operating Characteristic ◽

Area Under The Curve ◽

Roc Curves ◽

Diagnostic Value ◽

Differentially Expressed Mirnas ◽

E Box ◽

Aggressive Breast Cancer ◽

Potential Biomarkers

Inflammatory breast cancer (IBC) is a rare yet aggressive breast cancer variant, associated with a poor prognosis. The major challenge for IBC is misdiagnosis due to the lack of molecular biomarkers. We profiled dysregulated expression of microRNAs (miRNAs) in primary samples of IBC and non-IBC tumors using human breast cancer miRNA PCR array. We discovered that 28 miRNAs were dysregulated (10 were upregulated, while 18 were underexpressed) in IBC vs. non-IBC tumors. We identified 128 hub genes, which are putative targets of the differentially expressed miRNAs and modulate important cancer biological processes. Furthermore, our qPCR analysis independently verified a significantly upregulated expression of miR-181b-5p, whereas a significant downregulation of miR-200b-3p, miR-200c-3p, and miR-203a-3p was detected in IBC tumors. Receiver operating characteristic (ROC) curves implied that the four miRNAs individually had a diagnostic accuracy in discriminating patients with IBC from non-IBC and that miR-203a-3p had the highest diagnostic value with an AUC of 0.821. Interestingly, a combination of miR-181b-5p, miR-200b-3p, and miR-200c-3p robustly improved the diagnostic accuracy, with an area under the curve (AUC) of 0.897. Intriguingly, qPCR revealed that the expression of zinc finger E box-binding homeobox 2 (ZEB2) mRNA, the putative target of miR-200b-3p, miR-200c-3p, and miR-203a-3p, was upregulated in IBC tumors. Overall, this study identified a set of miRNAs serving as potential biomarkers with diagnostic relevance for IBC.

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Molecular and Functional Roles of MicroRNAs in the Progression of Hepatocellular Carcinoma—A Review

International Journal of Molecular Sciences ◽

10.3390/ijms21218362 ◽

2020 ◽

Vol 21 (21) ◽

pp. 8362

Author(s):

Kyoko Oura ◽

Asahiro Morishita ◽

Tsutomu Masaki

Keyword(s):

Hepatocellular Carcinoma ◽

Control Cell ◽

Messenger Rnas ◽

Functional Roles ◽

Multiple Risk Factors ◽

Biological Phenomena ◽

Viral Hepatitis B ◽

Novel Biomarkers ◽

Non Coding Rnas ◽

Made In

Liver cancer is the fourth leading cause of cancer deaths globally, of which hepatocellular carcinoma (HCC) is the major subtype. Viral hepatitis B and C infections, alcohol abuse, and metabolic disorders are multiple risk factors for liver cirrhosis and HCC development. Although great therapeutic advances have been made in recent decades, the prognosis for HCC patients remains poor due to late diagnosis, chemotherapy failure, and frequent recurrence. MicroRNAs (miRNAs) are endogenous, non-coding RNAs that regulate various molecular biological phenomena by suppressing the translation of target messenger RNAs (mRNAs). miRNAs, which often become dysregulated in malignancy, control cell proliferation, migration, invasion, and development in HCC by promoting or suppressing tumors. Exploring the detailed mechanisms underlying miRNA-mediated HCC development and progression can likely improve the outcomes of patients with HCC. This review summarizes the molecular and functional roles of miRNAs in the pathogenesis of HCC. Further, it elucidates the utility of miRNAs as novel biomarkers and therapeutic targets.

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