miR-515-3p, miR-623, miR-1272 and Notch3 protein as new biomarkers of Hepatocellular carcinoma

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Zahra Asefy ◽  
Sirus Hoseinnejhad ◽  
Aziz Eftekhari ◽  
Behrooz Shoukuhi
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Specificity ◽  
Main Role ◽  
Mirna Regulation ◽  
Expression Levels ◽  
Normal Tissues ◽  
Reverse Transcription Pcr ◽  
Specificity And Sensitivity ◽  
Notch Protein ◽  
New Biomarkers

Abstract Backgrounds Hepatocellular carcinoma (HCC) is a diversity of hepatocellular neoplasms and is more prevalence in people with chronic liver disease and cirrhosis. It has been revealed that modification in miRNA regulation possibly will be elaborated in HCC pathogenesis. Materials and methods In this research 40 samples of HCC subjects and 40 samples of healthy liver were considered. Total RNA was obtained from paraffin-embedded tissue blocks and miR-515, miR-623 and miR-1272 gene expression levels were quantified by Real-Time Quantitative Reverse Transcription PCR. Likewise, the Notch protein quantity was assayed in ffpe materials by immunohistochemistry. Results Our study disclosed that Notch protein deals was ominously elevated in cancer cells than healthy cells (p<0.05). Data analysis also displayed that miR-515, miR-623 and miR-1272 expression levels were 3.8, 4.7, and 2.9 fold in normal tissues, respectively (p<0.05). Furthermore, it was found that expression levels of these genes are not dependent by hepatitis B and hepatic cirrhosis and it could be used as a marker of high specificity and sensitivity for the diagnosis of HCC. Discussions Our study demonstrated main role of miR-515, miR-623 and miR-1272 in HCC pathogenesis and similarly disclosed that these genes expression could be utilized in HCC prognosis.

scholarly journals Multiple m6A RNA methylation modulators promote the malignant progression of hepatocellular carcinoma and affect its clinical prognosis

2020 ◽  
Author(s):  
Nanfang Qu ◽  
Sanyu Qin ◽  
Xuemei Zhang ◽  
Xiaotong Bo ◽  
Zhengchun Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Genome ◽  
Malignant Progression ◽  
World Health ◽  
Pathological Grade ◽  
Clinical Prognosis ◽  
Rna Methylation ◽  
Expression Levels ◽  
Normal Tissues ◽  
M6a Rna Methylation

Abstract Background: Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death in the world. N 6 -methyladenosine (m 6 A) RNA methylation is dynamically regulated by m 6 A RNA methylation modulators (“writer,” “eraser,” and “reader” proteins), which are associated with cancer occurrence and development. The purpose of this study was to explore the relationships between m 6 A RNA methylation modulators and HCC. Methods: First, using data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, we compared the expression levels of 13 major m6A RNA methylation modulators between HCC and normal tissues. Second, we applied consensus clustering to the expression data on the m 6 A RNA methylation modulators to divide the HCC tissues into two subgroups (clusters 1 and 2), and we compared the clusters in terms of overall survival (OS), World Health Organization (WHO) stage, and pathological grade. Third, using least absolute shrinkage and selection operator (LASSO) regression, we constructed a risk signature involving the m 6 A RNA methylation modulators that affected OS in TCGA and ICGC analyses. Results: We found that the expression levels of 12 major m6A RNA methylation modulators were significantly different between HCC and normal tissues. After dividing the HCC tissues into clusters 1 and 2, we found that cluster 2 had poorer OS, higher WHO stage, and higher pathological grade. Four m 6 A RNA methylation modulators (YTHDF1, YTHDF2, METTL3, and KIAA1429) affecting OS in the TCGA and ICGC analyses were selected to construct a risk signature, which was significantly associated with WHO stage and was also an independent prognostic marker of OS. Conclusions: In summary, m 6 A RNA methylation modulators are key participants in the malignant progression of HCC and have potential value in prognostication and treatment decisions.

RNA sequencing identifies two novel liver-specific long noncoding RNAs with potential diagnostic value in hepatocellular carcinoma

2021 ◽  
Author(s):  
Chao Tan ◽  
Xi Zeng ◽  
Meile Mo ◽  
Xiaoyun Ma ◽  
Qiuli Liang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Rna Sequencing ◽  
Reverse Transcription ◽  
Expression Profiles ◽  
Noncoding Rnas ◽  
Area Under The Curve ◽  
Long Noncoding Rnas ◽  
Normal Tissues ◽  
Quantitative Reverse Transcription Pcr ◽  
Reverse Transcription Pcr

Aim: To explore the expression profiles of long noncoding RNAs (lncRNAs) and identify novel lncRNAs as biomarkers for early diagnosis and therapy of hepatocellular carcinoma (HCC). Materials & methods: Expression profiles of lncRNAs and mRNAs in five paired HCC and adjacent normal tissues were obtained by RNA sequencing. Eight lncRNAs, including two novel liver-specific lncRNAs (NONHSAT059247.2 and NONHSAT013897.2), were validated in another 74 pairs of HCC and adjacent normal tissues by quantitative reverse transcription PCR. Results: The results of quantitative reverse transcription PCR showed that NONHSAT252133.1, NONHSAT112116.2 and NONHSAT242657.1 were significantly upregulated in HCC tissues, whereas NONHSAT169790.1, NONHSAT059247.2 and NONHSAT013897.2 were significantly downregulated. Two liver-specific lncRNAs demonstrated excellent diagnostic performance: NONHSAT059247.2 (area under the curve = 0.941, 95% CI: 0.902–0.979, p < 0.0001), NONHSAT013897.2 (area under the curve = 0.944, 95% CI: 0.906–0.983, p < 0.0001). Conclusion: The liver-specific lncRNAs NONHSAT059247.2 and NONHSAT013897.2, may provide new biomarkers for the future study on diagnosis, therapy, and mechanisms of HCC.

scholarly journals Concomitant use of heat-shock protein 70, glutamine synthetase and glypican-3 is useful in diagnosis of HBV-related hepatocellular carcinoma with higher specificity and sensitivity

2018 ◽  
Author(s):  
Bita Moudi ◽  
Zahra Heidari ◽  
Hamidreza Mahmoudzadeh-Sagheb ◽  
Seyed-Moayed Alavian ◽  
Kamran B. Lankarani ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Sensitivity And Specificity ◽  
Heat Shock Protein 70 ◽  
Expression Patterns ◽  
Control Group ◽  
Quantitative Real Time Pcr ◽  
Normal Tissues ◽  
The Third ◽  
Specificity And Sensitivity ◽  
Iranian Patients

Hepatocellular carcinoma is the third leading cause of cancer-related death worldwide and late diagnosis is the main cause of death in HCC patients. In this study expression patterns of HSP70, GPC3 and GS and their relationships with pathogenesis of HCC in Iranian patients were investigated. The expression of HSP70, GPC3 and GS were determined by immunohistochemistry and quantitative real-time PCR (q-PCR) methods, using 121 cases from patients with HBV alone, HCC without HBV, HBV+HCC and 30 normal tissues as control group. HSP70, GPC3 and GS were expressed in higher levels in HBV-related HCC samples compared to HBV alone group. The results showed that the labeling index of HSP70, GPC3 and GS are correlated with immunohistochemical and molecular expressions of HSP70, GPC3 and GS. The sensitivity and specificity for HCC diagnosis were 43.4% and 89.7% for HSP70, 64.3% and 90.4% for GPC3, and 60.7% and 94.3% for GS, respectively. The sensitivity and specificity of the panels with 3, 2 and 1 positive markers, regardless of which one, were 21.6% and 100%, 51.3% and 100% and 93.4% and 80.5% respectively. The current study demonstrated an association between HSP70, GPC3 and GS expressions and HBV-related HCC in our population. It was concluded that HSP70, GPC3 and GS expressions could be useful biomarkers for increasing the specificity and sensitivity of HCC diagnosis to acceptable level. Also, proper combinations of these 3 markers could improve diagnostic accuracy.

scholarly journals Multiple m6A RNA methylation modulators promote the malignant progression of hepatocellular carcinoma and affect its clinical prognosis

2019 ◽  
Author(s):  
Nanfang Qu ◽  
Haixing Jiang ◽  
Sanyu Qin ◽  
Xuemei Zhang ◽  
Zhengchun Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Genome ◽  
Malignant Progression ◽  
World Health ◽  
Pathological Grade ◽  
Clinical Prognosis ◽  
Rna Methylation ◽  
Expression Levels ◽  
Normal Tissues ◽  
M6a Rna Methylation

Abstract Background: Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death in the world. N 6 -methyladenosine (m 6 A) RNA methylation is dynamically regulated by m 6 A RNA methylation modulators (“writer,” “eraser,” and “reader” proteins), which are associated with cancer occurrence and development. The purpose of this study was to explore the relationships between m 6 A RNA methylation modulators and HCC. Methods: First, using data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, we compared the expression levels of 13 major m6A RNA methylation modulators between HCC and normal tissues. Second, we applied consensus clustering to the expression data on the m 6 A RNA methylation modulators to divide the HCC tissues into two subgroups (clusters 1 and 2), and we compared the clusters in terms of overall survival (OS), World Health Organization (WHO) stage, and pathological grade. Third, using least absolute shrinkage and selection operator (LASSO) regression, we constructed a risk signature involving the m 6 A RNA methylation modulators that affected OS in TCGA and ICGC analyses. Results: We found that the expression levels of 12 major m6A RNA methylation modulators were significantly different between HCC and normal tissues. After dividing the HCC tissues into clusters 1 and 2, we found that cluster 2 had poorer OS, higher WHO stage, and higher pathological grade. Four m 6 A RNA methylation modulators (YTHDF1, YTHDF2, METTL3, and KIAA1429) affecting OS in the TCGA and ICGC analyses were selected to construct a risk signature, which was significantly associated with WHO stage and was also an independent prognostic marker of OS. Conclusions: In summary, m 6 A RNA methylation modulators are key participants in the malignant progression of HCC and have potential value in prognostication and treatment decisions.

scholarly journals miR-203 Expression in Exfoliated Cells of Tongue Coating Represents a Sensitive and Specific Biomarker of Gastroesophageal Reflux Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Xiuli Yan ◽  
Shengliang Zhu ◽  
Hui Zhang
Keyword(s):  
Gastroesophageal Reflux Disease ◽  
Gastroesophageal Reflux ◽  
Mirna Expression ◽  
Reflux Disease ◽  
Validation Cohort ◽  
Roc Curves ◽  
Expression Levels ◽  
Reverse Transcription Pcr ◽  
Specificity And Sensitivity ◽  
Exfoliated Cells

Background and Aim. MicroRNAs (miRNAs) have been implicated in the pathophysiology of numerous human diseases including gastroesophageal reflux disease (GERD). The objective of this study was to investigate the miRNA expression of exfoliated cells of the tongue in patients with GERD versus healthy controls (Ctrls).Methods. Using quantitative reverse-transcription PCR (qRT-PCR), expression levels of six candidate miRNAs (miR-143, miR-145, miR-192, miR-194, miR-203, and miR-205) were examined across a discovery cohort of patients with GERD (n=24) versus Ctrls (n=24). These findings were confirmed across a validation cohort (GERD,n=142; Ctrls,n=48). Differences in miRNA expression levels were evaluated using the Mann-WhitneyUtest while the specificity and sensitivity were obtained using receiver-operator characteristic (ROC) curves.Results. miR-203 was significantly downregulated in GERD patients as compared to Ctrls (P<0.0001) with ROC curve of 0.94 (95% CI: 0.90–0.97). The sensitivity and the specificity of miR-203 were 91.7% and 87.3%, respectively, in the GERD and Ctrls. These results suggest that miR-203 may be a useful diagnostic marker for discriminating GERD from Ctrls.Conclusions. miR-203 testing may assist in the diagnosis of patients with symptoms suggestive of GERD.

scholarly journals miR-139-5p Loss-Mediated WTAP Activation Contributes to Hepatocellular Carcinoma Progression by Promoting the Epithelial to Mesenchymal Transition

2021 ◽  
Vol 11 ◽  
Author(s):  
Wenli Liu ◽  
Xuewei Gao ◽  
Xiaolong Chen ◽  
Na Zhao ◽  
Ying Sun ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Epithelial To Mesenchymal Transition ◽  
Wilms Tumor ◽  
Clinical Stage ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Normal Tissues ◽  
Proliferation And Invasion

Background: Hepatocellular carcinoma (HCC) is a primary aggressive gastrointestinal neoplasm that affects patients worldwide. It has been shown that Wilms' tumor 1-associating protein (WTAP) is frequently upregulated in various cancers. However, the potential role of WTAP in HCC remains largely unknown.Methods: The expression levels of WTAP in human HCC tissues were determined by the western blotting and immunohistochemical (IHC) staining. A correlation between the WTAP expression, clinicopathological features, and the HCC prognosis was analyzed. The WTAP expression was silenced by short hairpin RNA (shRNA), and effects of the knockdown of WTAP on the proliferation and invasion of HCC cells were assessed. The microRNAs (miRNAs) involved in the regulation of the WTAP expression were identified by a bioinformatics analysis and further confirmed by in vitro assays.Results: The expression levels of WTAP in liver cancer tissues were significantly elevated and compared with those in the adjacent normal tissues and significantly correlated with the clinical stage and prognosis in patients with HCC. Further investigation revealed that the knockdown of WTAP drastically suppressed HCC cell proliferation and invasion abilities. Luciferase reporter assay and validation experiments confirmed that WTAP was a direct target of miR-139-5p. Moreover, the overexpression of WTAP could partly abolish the inhibitory effects of miR-139-5p on the HCC cell growth and invasion. Mechanistically, we revealed that the miR-139-5p/WTAP axis regulated the HCC progression by controlling the epithelial to mesenchymal transition (EMT).Conclusions: In summary, the results indicate that WTAP is a potential oncogene in HCC and miR-139-5p negatively regulates the WTAP expression. MiR-139-5p/WTAP can be utilized as a potential therapeutic target for HCC.

scholarly journals Long Noncoding RNA GATA3-AS1 Promotes Cell Proliferation and Metastasis in Hepatocellular Carcinoma by Suppression of PTEN, CDKN1A, and TP53

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Xuee Luo ◽  
Ning Zhou ◽  
Le Wang ◽  
Qinghua Zeng ◽  
Hongying Tang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cell Counting ◽  
Cell Growth And Migration ◽  
Expression Levels ◽  
Normal Tissues ◽  
Proliferation And Metastasis ◽  
And Migration ◽  
Cell Proliferation And Metastasis

Background. Long noncoding RNAs (lncRNAs) have been known to play important roles in the progression of various types of human cancer. LncRNA GATA3 antisense RNA 1, GATA3-AS1, has been reported to be associated with T-cell development and differentiation. However, the expression pattern and function of GATA3-AS1 in hepatocellular carcinoma (HCC) remain unknown. Methods. Real-time quantitative PCR (RT-qPCR) assay was conducted to detect GATA3-AS1 expression levels in 80 cases of pairs HCC tissues and matched normal tissues. Chi-squared (χ2) test was used to analyze the correlation between GATA3-AS1 expression and clinicopathologic variables. Survival curves were plotted using the Kaplan–Meier method and were compared via the log-rank test. The cell counting kit-8 (CCK-8) and wound scratch assays were applied to detect the effect of GATA3-AS1 knockdown and overexpression on cell growth and migration of HCC. RT-qPCR was performed for the detection of the phosphatase and tensin homolog (PTEN), cyclin-dependent kinase inhibitor 1A (CDKN1A), and tumor protein p53 (TP53) expression in HCC cells after GATA3-AS1 knockdown and overexpression. Results. GATA3-AS1 was significantly upregulated in HCC tissues compared with matched normal tissues. The high expression of GATA3-AS1 was significantly correlated with larger tumor size, advanced TNM stage, and more lymph node metastasis. High GATA3-AS1 expression was markedly correlated with shorter overall survival times of HCC patients. Furthermore, knockdown of GATA3-AS1 obviously inhibited Hep3B and HCCLM3 cell growth and migration, whereas overexpression of GATA3-AS1 had the opposite effects. In addition, GATA3-AS1 knockdown resulted in upregulated expression levels of tumor-suppressive genes, PTEN, CDKN1A, and TP53, in Hep3B and HCCLM3 cells, while restoration of GATA3-AS1 decreased PTEN, CDKN1A, and TP53 expression levels. Conclusion. Our data suggested that GATA3-AS1 promotes cell proliferation and metastasis of HCC by suppression of PTEN, CDKN1A, and TP53.

scholarly journals The bioinformatics and experimental analysis of AlkB family for prognosis and immune cell infiltration in hepatocellular carcinoma

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12123
Author(s):  
Bi Peng ◽  
Yuanliang Yan ◽  
Zhijie Xu
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Metal Ion ◽  
Immune Cell ◽  
Disease Free Survival ◽  
Normal Liver ◽  
Expression Levels ◽  
Normal Tissues ◽  
Molecular Profiles

Background Serving as N6-methyladenosine demethylases, the AlkB family is involved in the tumorigenesis of hepatocellular carcinoma (HCC). However, the molecular profiles and clinical values of the AlkB family in HCC are not well known. Methods Several bioinformatics tools and in vitro experiments were used to identify the immune-related profiles and prognostic values of AlkB family in HCC. Results In this study expression levels of ALKBH1/2/3/4/7 were all remarkably increased in HCC tissues when compared with normal tissues. Quantitative PCR (qPCR) and immunohistochemistry were used to validate the expression of AlkB family members in HCC tissues and normal liver tissues. In addition, high expression levels of ALKBH4 were negatively correlated with overall survival (OS) and disease-free survival (DFS) in patients with HCC. Increased ALKBH4 was also associated with pathological stage in HCC patients. The molecular profiles of AlkB family in HCC were mainly associated with peptidyl-serine modification, peptidyl-tyrosine modification, regulation of metal ion transport, etc. Furthermore, tumor-infiltrating immune cell analysis indicated that ALKBH1/2/3/4/5/6/7/8 and FTO were related to the infiltration of different immune cell, such as CD8+ T cells, macrophages, neutrophils, dendritic cells and CD4+ T cells. We also discovered that the methylation levels of ALKBH1/2/4/5/6/8 and FTO were remarkably reduced in HCC tissues. Conclusions Collectively, our findings may deepen the understanding of specific molecular profiles of the AlkB family in HCC pathology. In particular, ALKBH4 could serve as a promising prognostic candidate for treating HCC, and these results might potentiate the development of more reliable therapeutic strategies for patients with HCC.

scholarly journals Multiple m6A RNA methylation modulators promote the malignant progression of hepatocellular carcinoma and affect its clinical prognosis

2020 ◽  
Author(s):  
Nanfang Qu ◽  
Sanyu Qin ◽  
Xuemei Zhang ◽  
Xiaotong Bo ◽  
Zhengchun Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Genome ◽  
Malignant Progression ◽  
World Health ◽  
Pathological Grade ◽  
Clinical Prognosis ◽  
Rna Methylation ◽  
Expression Levels ◽  
Normal Tissues ◽  
M6a Rna Methylation

Abstract Background: Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death in the world. N 6 -methyladenosine (m 6 A) RNA methylation is dynamically regulated by m 6 A RNA methylation modulators (“writer,” “eraser,” and “reader” proteins), which are associated with cancer occurrence and development. The purpose of this study was to explore the relationships between m 6 A RNA methylation modulators and HCC. Methods: First, using data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, we compared the expression levels of 13 major m6A RNA methylation modulators between HCC and normal tissues. Second, we applied consensus clustering to the expression data on the m 6 A RNA methylation modulators to divide the HCC tissues into two subgroups (clusters 1 and 2), and we compared the clusters in terms of overall survival (OS), World Health Organization (WHO) stage, and pathological grade. Third, using least absolute shrinkage and selection operator (LASSO) regression, we constructed a risk signature involving the m 6 A RNA methylation modulators that affected OS in TCGA and ICGC analyses. Results: We found that the expression levels of 12 major m6A RNA methylation modulators were significantly different between HCC and normal tissues. After dividing the HCC tissues into clusters 1 and 2, we found that cluster 2 had poorer OS, higher WHO stage, and higher pathological grade. Four m 6 A RNA methylation modulators (YTHDF1, YTHDF2, METTL3, and KIAA1429) affecting OS in the TCGA and ICGC analyses were selected to construct a risk signature, which was significantly associated with WHO stage and was also an independent prognostic marker of OS. Conclusions: In summary, m 6 A RNA methylation modulators are key participants in the malignant progression of HCC and have potential value in prognostication and treatment decisions.

scholarly journals Potential Markers for Detection and Monitoring of Ovarian Cancer

2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Brandon J. D. Rein ◽  
Sajal Gupta ◽  
Rima Dada ◽  
Joelle Safi ◽  
Chad Michener ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Early Detection ◽  
Early Stage ◽  
Survival Rates ◽  
High Specificity ◽  
Protein Markers ◽  
Specificity And Sensitivity ◽  
Novel Biomarkers ◽  
New Biomarkers ◽  
Current Screening

This paper reviews current screening techniques as well as novel biomarkers and their potential role in early detection of ovarian cancer. Ovarian cancer is one of the most common reproductive cancers and has the highest mortality rate amongst gynecologic cancers. Because most ovarian cancer diagnoses occur in the late stages of the disease, five-year survival rates fall below 20%. To improve survival rates and to lower mortality rates for ovarian cancer, improved detection at early stages of the disease is needed. Current screening approaches include tumor markers, ultrasound, or a combination. Efforts are underway to discover new biomarkers of ovarian cancer in order to surmount the obstacles in early-stage diagnosis. Among serum protein markers, HE4 and mesothelin can augment CA125 detection providing higher sensitivity and specificity due to the presence of these proteins in early-stage ovarian cancer. Detection testing that includes methylation of the MCJ gene and increased expression of vascular endothelial growth factor is correlated to poor prognosis and may predict patient survival outcome. Detection testing of biomarkers with long-term stability and combination panels of markers, will likely lead to effective screening strategies with high specificity and sensitivity for early detection of ovarian cancer.

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