Identification of Circulating Exosomal miR-101 and miR-125b Panel Act as a Potential Biomarker for Hepatocellular Carcinoma

Background. Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with high mortality, and there is an urgent need of new diagnosis measures. This study is aimed at investigating whether circulating exosomal miRNAs could act as biomarkers for the diagnosis of HCC. Methods. A four-stage strategy was adopted in this study. Candidate miRNA was selected by comprehensive analysis of four GEO datasets and TCGA database. The expression of candidate miRNAs in serum exosomal samples were examined through qRT-PCR. The diagnostic utility of the final validated miRNAs was examined by receiver operating characteristic (ROC) curve analysis. Results. After synthetical analysis of four GEO datasets, six miRNAs were selected as candidates due to their higher differential fold change. miR-101 and miR-125b were selected as candidate miRNAs to further investigate their potential as biomarkers for HCC due to their differential fold change and their influence on overall survival based on the TCGA database. As a result, miR-101 and miR-125b expressions were remarkably downregulated in both tissues and serum exosomes of patients with HCC. The area under the ROC curves (AUCs) of circulating exosomal miR-101 and miR-125b were 0.894 (95% CI, 0.793–0.994) and 0.812 (95% CI, 0.675–0.950), respectively. The combination of the two miRNAs presented higher diagnostic utility for HCC ( AUC = 0.953 ). Conclusion. The exosomal miR-101 and miR-125b panel in the serum may act as a noninvasive biomarker for HCC detection.

Download Full-text

Circular RNA Hsa_Circ_0091579 Serves as a Diagnostic and Prognostic Marker for Hepatocellular Carcinoma

Cellular Physiology and Biochemistry ◽

10.1159/000495230 ◽

2018 ◽

Vol 51 (1) ◽

pp. 290-300 ◽

Cited By ~ 18

Author(s):

Chenxing Zhang ◽

Chenyue Zhang ◽

Jiamao Lin ◽

Haiyong Wang

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Tumors ◽

Expression Profiles ◽

Critical Role ◽

Roc Curves ◽

Altered Expression ◽

Qrt Pcr ◽

Specificity And Sensitivity ◽

Tumor Tissues ◽

Potential Biomarker

Background/Aims: An increasing number of studies have suggested that circular RNAs (circRNAs) have vital roles in carcinogenesis and tumor progression. However, the function of circRNAs in hepatocellular carcinoma (HCC) remains poorly characterized. Methods: We investigated the levels of circRNAs in patients with HCC to identify potential diagnostic biomarkers. We examined circRNA expression profiles in liver tumors and paired non-cancerous liver tissues from three HCC patients with cancer thrombus using a circRNA microarray. Bioinformatics analysis was performed to find circRNAs with significantly altered expression levels between tumors and their paired non-tumor tissues. We confirmed our initial findings by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Receiver operating characteristic (ROC) curves were also applied to identify a candidate circRNA with the optimal specificity and sensitivity. Finally, X-tile software was adopted to calculate the most efficient cut-off value for hsa_circ_0091579 expression. Results: Microarray analysis identified 20 unique circRNAs that were differentially expressed between tumor and non-tumor tissues (P < 0.05). The expression of these 20 circRNAs was verified by qRT-PCR. The expression of hsa_circ_16245-1 and hsa_circ_0091579 mRNA was consistent with their levels as tested by the microarray. The ROC curves showed that both hsa_circ_16245-1 and hsa_circ_0091579 had favorable specificity and sensitivity. We further confirmed that hsa_circ_0091579 was significantly upregulated in HCC and its high expression was intimately associated with a worse overall survival in patients with HCC. Conclusion: Hsa_circ_0091579 may play a critical role in HCC progression and serve as a potential biomarker for the prognosis of patients with HCC.

Download Full-text

Identification of MCM4 as a Prognostic Marker of Hepatocellular Carcinoma

BioMed Research International ◽

10.1155/2021/7479326 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Huandi Zhou ◽

Le Jiang ◽

Guohui Wang ◽

Linlin Su ◽

Liubing Hou ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Real Time ◽

Roc Curve ◽

Real Time Pcr ◽

Malignant Tumors ◽

Nodal Metastasis ◽

Cellular Heterogeneity ◽

Survival Prediction ◽

Roc Curve Analysis ◽

Potential Biomarker

Object. Hepatocellular carcinoma is one of the most common malignant tumors worldwide owing to its complicated molecular and cellular heterogeneity and its high incidence rate every year. It is an urgent need to search for new efficient molecular markers of HCC to reduce mortality and improve HCC prognosis. In this article, MCM4, a member of a family of proteins closely related to DNA replication and cell proliferation, was selected as a potential biomarker of HCC prognosis. Methods. MCM4 expression difference in HCC were analyzed from TCGA and GEO data and verified by real-time PCR and western blot. ROC curve was used to analyze the diagnostic value of MCM4 and AFP. Additionally, the relationship between MCM4 and stage or nodal metastasis status or grade or age in TCGA cohort with HCC was observed from the UALCAN website. The univariate and multivariate Cox and functional analyses were done to explore the prognostic value of MCM4 in TCGA cohort. Results. It was found that MCM4 was significantly highly expressed in HCC tissues from TCGA, GEO, and experimental data. Furthermore, ROC curve analysis showed that MCM4 was superior to be a diagnostic biomarker than AFP from TCGA ( AU C MCM 4 = 0.9461 , AU C AFP = 0.7056 ) and GEO (GSE19665: AU C MCM 4 = 0.8800 , AU C AFP = 0.5100 ; GSE64041 AU C MCM 4 = 0.8038 , AU C AFP = 0.6304 ). AUC of MCM4 from real-time PCR result in 60 pairs of HCC and adjacent tissues was 0.7172, demonstrating the prediction value of MCM4. Besides, different expression tendencies of MCM4 among different stages or nodal metastasis status or grade or age were observed from the UALCAN website. In addition, multiROC analysis showed the advantage of MCM4 as a survival prediction at 1, 3, and 5 years with the higher AUC at 0.69 of 1 year, 0.65 of 3 years, and 0.61 of 5 years. It was shown that MCM4 was independently associated with OS in univariate and multivariate Cox analysis. And GSEA displayed that MCM4 was highly enriched in KEGG_CELL_CYCLE signaling pathway following higher correlation positively with CDC6, PLK1, CRC1, and BUB1B in HCC. Conclusion. MCM4 might be a potential biomarker in guiding the prognostic status of HCC patients.

Download Full-text

Evaluation of the Diagnostic Potential of a Plasma Exosomal miRNAs Panel for Gastric Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.683465 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jiajia Yang ◽

Xuan Li ◽

Shuchun Wei ◽

Lei Peng ◽

Huaiming Sang ◽

...

Keyword(s):

Gastric Cancer ◽

Roc Curves ◽

Diagnostic Efficiency ◽

Roc Curve Analysis ◽

Kaplan Meier ◽

Diagnostic Potential ◽

Training Stage ◽

Exosomal Mirnas ◽

Tumor Phenotype

PurposeGastric cancer (GC) is often difficult to diagnose early in the disease and remains one of the most frequently occurring malignancies. This investigation looks at the diagnostic potential of a specific plasma exosomal miRNAs panel for GC.MethodsThis study analyzed 216 individual peripheral blood samples. 2 GEO datasets were analyzed and two miRNAs were selected - plasma exosomal miR-195-5p and miR-211-5p. Quantitative reverse-transcriptase PCR (qRT–PCR) was used to assess relative expressions and receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic efficiency of miR-195-5p and miR-211-5p panel. The Kaplan-Meier method was used to assess the prognostic value of plasma exosomal miR-195-5p and miR-211-5p.ResultsGC patients possessed notably raised plasma levels of exosomal miR-195-5p and miR-211-5p. The area under ROC curves (AUCs) of miR-195-5p, miR-211-5p were 0.745, 0.798 in the screening phase and 0.762, 0.798 in the training stage respectively. GC was able to be diagnosed more accurately when both miRNAs were interpreted together (AUC=0.820 in the validation stage). Poorer prognosis was observed in GC patients who had plasma exosomal miR-195-5p and miR-211-5p of higher levels. In vitro experiments also confirmed that miR-195-5p and miR-211-5p is able to be transmitted between cells, and works to enhance tumor invasion, migration and proliferation while inhibiting cell apoptosis.ConclusionPlasma exosomal miR-195-5p and miR-211-5p may become potential biomarkers for GC diagnosis, and may be useful in predicting tumor phenotype.

Download Full-text

Diagnostic value of plasma HSP90α levels for detection of hepatocellular carcinoma

BMC Cancer ◽

10.1186/s12885-019-6489-0 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 2

Author(s):

Wene Wei ◽

Mengshu Liu ◽

Shufang Ning ◽

Jing Wei ◽

Jianhong Zhong ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Heat Shock Protein 90 ◽

Diagnostic Value ◽

Initial Diagnosis ◽

Hepatic Hemangioma ◽

Diagnostic Efficiency ◽

Roc Curve Analysis ◽

Major Health Problem ◽

Healthy Donors ◽

Potential Biomarker

Abstract Background Hepatocellular carcinoma (HCC) is a major health problem worldwide. However, the popular tumor marker, AFP, lacks sensitivity although its specificity is high. Tissue biopsy is an invasive operation and may increase the risk of needle-track metastases. Heat shock protein 90 (HSP90) is a potential biomarker for tumor diagnosis and prognosis. This study aims to determine whether levels of plasma HSP90α in HCC patients can be used as a cost-effective and simple test for the initial diagnosis of the disease. Methods Plasma samples were collected from 659 HCC patients, 114 secondary hepatic carcinoma (SHC) patients, 28 hepatic hemangioma patients and 230 healthy donors. The levels of HSP90α were measured by ELISA. Results The levels of plasma HSP90α in HCC patients were significantly higher than in healthy donors and in patients with hepatic hemangioma or SHC (144.08 ± 4.98, 46.81 ± 1.11, 61.56 ± 8.20 and 111.96 ± 10.08 ng/mL, respectively; p < 0.05 in all cases). The levels were associated with age (p = 0.001), BCLC stage (p < 0.001), levels of AFP (p < 0.001), tumor size (p < 0.001), tumor number (p < 0.001), PVTT (p < 0.001), EHM (p < 0.001) and Child-Pugh stage in the HCC cohort. In addition, the levels of plasma HSP90α showed an upward trend along with the progression of the BCLC stage. ROC curve analysis showed that compared to AFP (AUC 0.922, 95%CI 0.902–0.938) or HSP90α (AUC 0.836, 95%CI 0.810–0.860), the combination of HSP90α and AFP (AUC0.943, 95%CI 0.925–0.957) significantly improved the diagnostic efficiency for HCC patients. Conclusion The results suggest that plasma Hsp90 α levels can be used as an initial diagnosis for patients with HCC in both rural and cosmopolitan settings.

Download Full-text

A Signature of Three MicroRNAs is a Potential Diagnostic Biomarker for Glioblastoma

10.21203/rs.3.rs-1048138/v1 ◽

2021 ◽

Author(s):

Ali Hosein Yazdi ◽

vajiheh zarrinpour ◽

Elham Moslemi ◽

Mohammad Mahdi ForghaniFard

Keyword(s):

In Silico ◽

Poor Prognosis ◽

Biological Effects ◽

Malignant Neoplasm ◽

Roc Curves ◽

Clinicopathological Characteristics ◽

Roc Curve Analysis ◽

Reverse Transcription Pcr ◽

Potential Biomarker ◽

The Central Nervous System

Abstract Background: Glioblastoma (GBM) is by far the most common primary malignant neoplasm of the central nervous system. In spite ofsome progress in diagnosis and treatment, GBM patients still have a poor prognosis. Hence, to improve GBM diagnosis, finding novel non-invasive biomarkers, e.g., miRNA-based biomarkers,is of importance.Methods: A pair of 50 GBM and healthy samples were used. The expression of each candidate miRNA (i.e.,hsa-let-7c-5p, hsa-miR-206-5p, and hsa-miR-1909-5p)was measured using quantitative reverse transcription PCR. To show the roles of each miRNA and their biological effects on GBM development, in silico tools were used. Receiver operating characteristic (ROC) curves were performed to assess the diagnostic accuracy of each miRNA; the possible association of their expression with clinicopathological characteristics wasalso analyzed. To find out any association between the miRNA expression and GBM prognosis, in silico tools were used.Results: We showed the downregulation of hsa-let-7c-5pand hsa-miR-206-5p, and upregulation of hsa-miR-1909-5p in GBM tumor compared to healthy samples. No association was detected between the expression of each candidate miRNA and ‘sex’. Except for hsa-let-7c-5p, other miRNAs did not show any correlation with ‘age’ status. ROC curve analysis showed that the signature of candidate miRNAsis a potential biomarker distinguishing between GBM and healthy samples. Only hsa-miR-206-5p showed the association with poor prognosis in GBM patients.Conclusions: We demonstrated that the dysregulation of three candidate miRNAs may be used as a biomarker for GBM diagnosis. These results are beneficial in clinical management of GBM patients.

Download Full-text

Plasma-derived exosomal miR-4732-5p is a promising noninvasive diagnostic biomarker for epithelial ovarian cancer

Journal of Ovarian Research ◽

10.1186/s13048-021-00814-z ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Jingjing Liu ◽

Jigeun Yoo ◽

Jung Yoon Ho ◽

Yuyeon Jung ◽

Sanha Lee ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Healthy Subjects ◽

Early Stage ◽

Roc Curves ◽

Pcr Analysis ◽

Rt Pcr ◽

Potential Biomarker ◽

Exosomal Mirnas ◽

Exosomal Mirna

Abstract Background Exosomal miRNAs regulate gene expression and play important roles in several diseases. We used exosomal miRNA profiling to investigate diagnostic biomarkers of epithelial ovarian cancer (EOC). Methods In total, 55 individuals were enrolled, comprising healthy (n = 21) and EOC subjects (n = 34). Small mRNA (smRNA) sequencing and real-time PCR (RT-PCR) were performed to identify potential biomarkers. Receiver operating characteristic (ROC) curves were conducted to determine biomarker sensitivity and specificity. Results Using smRNA sequencing, we identified seven up-regulated (miR-4732-5p, miR-877-5p, miR-574-3p, let-7a-5p, let-7b-5p, let-7c-5p, and let-7f-5p) and two down-regulated miRNAs (miR-1273f and miR-342-3p) in EOC patients when compared with healthy subjects. Of these, miR-4732-5p and miR-1273f were the most up-regulated and down-regulated respectively, therefore they were selected for RT-PCR analysis. Plasma derived exosomal miR-4732-5p had an area under the ROC curve of 0.889, with 85.7% sensitivity and 82.4% specificity in distinguishing EOC patients from healthy subjects (p<0.0001) and could be a potential biomarker for monitoring the EOC progression from early stage to late stage (p = 0.018). Conclusions Plasma derived exosomal miR-4732-5p may be a promising candidate biomarker for diagnosing EOC.

Download Full-text

Baseline apparent diffusion coefficients: Validation study of new predictor of survival in patients with unresectable hepatocellular carcinoma following chemoembolization

Journal of X-Ray Science and Technology ◽

10.3233/xst-200827 ◽

2021 ◽

pp. 1-10

Author(s):

Lichao Xu ◽

Shiqin Wang ◽

Shengping Wang ◽

Ying Wang ◽

Wentao Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Roc Curve ◽

Cox Regression ◽

Response To Treatment ◽

Roc Curve Analysis ◽

Adc Value ◽

Apparent Diffusion Coefficients ◽

Apparent Diffusion ◽

Response Biomarker ◽

The Difference

OBJECTIVES: To investigate whether the baseline apparent diffusion coefficient (ADC) can predict survival in the hepatocellular carcinoma (HCC) patients receiving chemoembolization. MATERIALS AND METHODS: Diffusion-weighted MR imaging of HCC patients is performed within 2 weeks before chemoembolization. The ADC of the largest index lesion is recorded. Responses are assessed by mRECIST after the start of the second course of chemoembolization. Receiver operating characteristic (ROC) curve analysis is performed to evaluate the diagnostic performance and determine optimal cut-off values. Cox regression and Kaplan–Meier survival analyses are used to explore the differences in overall survival (OS) between the responders and non-responders. RESULTS: The difference is statistically significant in the baseline ADC between the responders and non-responders (P < 0.001). ROC analyses indicate that the baseline ADC value is a good predictor of response to treatment with an area under the ROC curve (AUC) of 0.744 and the optimal cut-off value of 1.22×10–3 mm2/s. The Cox regression model shows that the baseline ADC is an independent predictor of OS, with a 57.2% reduction in risk. CONCLUSION: An optimal baseline ADC value is a functional imaging response biomarker that has higher discriminatory power to predict tumor response and prolonged survival following chemoembolization in HCC patients.

Download Full-text