The Diagnostic Value of Chemokine/Chemokine Receptor Pairs in Hepatocellular Carcinoma and Colorectal Liver Metastasis

Chemokines and their receptors have been proposed to play important roles in tumor progression and metastasis. To investigate their roles in the progression of primary and metastatic malignant liver tumors and their prognosis, we compared expression profiles of CXCL12/CXCR4, CCL20/CCR6, and CCL21/CCR7 in hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM). Immunohistochemistry was used to analyze the expression levels of the chemokine/chemokine receptor pairs in 29 HCC and 11 CRLM specimens and adjacent non-cancerous tissues, and correlations with clinicopathological variables and overall survival were determined. CCL20/CCR6 expression was higher in HCC than in adjacent non-cancerous tissues. High CCR6 expression in HCC was negatively associated with 5-year survival rate and was an independent prognostic factor for overall survival of HCC patients, whereas differences were not observed between CRLM and adjacent tissues. Furthermore, significantly higher expression of CCL21/CCR7 was found in CRLM than in HCC. In summary, the CCL20/CCR6 axis was elevated in HCC but not in CRLM, whereas the CCL21/CCR7 axis was elevated in CRLM but not in HCC.

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A High-Accuracy Model Based on Plasma miRNAs Diagnoses Intrahepatic Cholangiocarcinoma: A Single Center with 1001 Samples

Diagnostics ◽

10.3390/diagnostics11040610 ◽

2021 ◽

Vol 11 (4) ◽

pp. 610

Author(s):

Jie Hu ◽

Yi-Ning Wang ◽

Dan-Jun Song ◽

Jin-Peng Tan ◽

Ya Cao ◽

...

Keyword(s):

Intrahepatic Cholangiocarcinoma ◽

Validation Cohort ◽

Liver Tumors ◽

Characteristic Curve ◽

Diagnostic Value ◽

High Accuracy ◽

Clinical Value ◽

Malignant Liver Tumors ◽

Malignant Liver ◽

Performance Results

Objectives: Intrahepatic cholangiocarcinoma (iCCA) is a highly malignant cancer. More than 70% of patients are diagnosed at an advanced stage. The aim of this study was to evaluate the diagnostic value of plasma miR-21, miR-122, and CA19-9, hoping to establish a novel model to improve the accuracy for diagnosing iCCA. Materials and methods: Plasma miR-21 and miR-122 were detected in 359 iCCA patients and 642 controls (healthy, benign liver lesions, other malignant liver tumors). All 1001 samples were allocated to training cohort (n = 668) and validation cohort (n = 333) in a chronological order. A logistic regression model was applied to combine these markers. Area under the receiver operating characteristic curve (AUC) was used as an accuracy index to evaluate the diagnostic performance. Results: Plasma miR-21 and miR-122 were significantly higher in iCCA patients than those in controls. Higher plasma miR-21 level was significantly correlated with larger tumor size (p = 0.030). A three-marker model was constructed by using miR-21, miR-122 and CA19-9, which showed an AUC of 0.853 (95% CI: 0.824–0.879; sensitivity: 73.0%, specificity: 87.4%) to differentiate iCCA from controls. These results were subsequently confirmed in the validation cohort with an AUC of 0.866 (0.825–0.901). The results were similar for diagnosing early (stages 0–I) iCCA patients (AUC: 0.848) and CA19-9negative iCCA patients (AUC: 0.795). Conclusions: We established a novel three-marker model with a high accuracy based on a large number of participants to differentiate iCCA from controls. This model showed a great clinical value especially for the diagnosis of early iCCA and CA19-9negative iCCA.

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Hypervascular Benign and Malignant Liver Tumors That Require Differentiation from Hepatocellular Carcinoma: Key Points of Imaging Diagnosis

Liver Cancer ◽

10.1159/000343864 ◽

2014 ◽

Vol 3 (2) ◽

pp. 85-96 ◽

Cited By ~ 21

Author(s):

Takamichi Murakami ◽

Masakatsu Tsurusaki

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Tumors ◽

Imaging Diagnosis ◽

Key Points ◽

Malignant Liver Tumors ◽

Malignant Liver

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Expression and function of CXC and CC chemokines in human malignant liver tumors: A role for human monokine induced by ?-interferon in lymphocyte recruitment to hepatocellular carcinoma

Hepatology ◽

10.1002/hep.510300147 ◽

1999 ◽

Vol 30 (1) ◽

pp. 100-111 ◽

Cited By ~ 100

Author(s):

Khong F. Yoong ◽

Simon C. Afford ◽

Rebecca Jones ◽

Pav Aujla ◽

Shixin Qin ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Tumors ◽

Cc Chemokines ◽

Malignant Liver Tumors ◽

Malignant Liver ◽

And Function

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Sirt1 deacetylates and stabilizes p62 to promote hepato-carcinogenesis

Cell Death and Disease ◽

10.1038/s41419-021-03666-z ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Lifeng Feng ◽

Miaoqin Chen ◽

Yiling Li ◽

Muchun Li ◽

Shiman Hu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Cell Growth ◽

Knockout Mice ◽

Liver Tumors ◽

Underlying Mechanism ◽

Carcinoma Cells ◽

Conditional Knockout

Abstractp62/SQSTM1 is frequently up-regulated in many cancers including hepatocellular carcinoma. Highly expressed p62 promotes hepato-carcinogenesis by activating many signaling pathways including Nrf2, mTORC1, and NFκB signaling. However, the underlying mechanism for p62 up-regulation in hepatocellular carcinoma remains largely unclear. Herein, we confirmed that p62 was up-regulated in hepatocellular carcinoma and its higher expression was associated with shorter overall survival in patients. The knockdown of p62 in hepatocellular carcinoma cells decreased cell growth in vitro and in vivo. Intriguingly, p62 protein stability could be reduced by its acetylation at lysine 295, which was regulated by deacetylase Sirt1 and acetyltransferase GCN5. Acetylated p62 increased its association with the E3 ligase Keap1, which facilitated its poly-ubiquitination-dependent proteasomal degradation. Moreover, Sirt1 was up-regulated to deacetylate and stabilize p62 in hepatocellular carcinoma. Additionally, Hepatocyte Sirt1 conditional knockout mice developed much fewer liver tumors after Diethynitrosamine treatment, which could be reversed by the re-introduction of exogenous p62. Taken together, Sirt1 deacetylates p62 at lysine 295 to disturb Keap1-mediated p62 poly-ubiquitination, thus up-regulating p62 expression to promote hepato-carcinogenesis. Therefore, targeting Sirt1 or p62 is a reasonable strategy for the treatment of hepatocellular carcinoma.

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Malignant Liver Tumors in Childhood

Cancer in Childhood ◽

10.1007/978-1-4684-2070-8_22 ◽

1973 ◽

pp. 166-170

Author(s):

Sigmund H. Ein ◽

Clinton A. Stephens

Keyword(s):

Liver Tumors ◽

Malignant Liver Tumors ◽

Malignant Liver

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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.

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Exploration and validation of a novel prognostic signature based on comprehensive bioinformatics analysis in hepatocellular carcinoma

Bioscience Reports ◽

10.1042/bsr20203263 ◽

2020 ◽

Vol 40 (11) ◽

Author(s):

Xiaofei Wang ◽

Jie Qiao ◽

Rongqi Wang

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

Overall Survival ◽

Risk Score ◽

Expression Profiles ◽

Univariate Analysis ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Good Prediction ◽

Expression Levels

Abstract The present study aimed to construct a novel signature for indicating the prognostic outcomes of hepatocellular carcinoma (HCC). Gene expression profiles were downloaded from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases. The prognosis-related genes with differential expression were identified with weighted gene co-expression network analysis (WGCNA), univariate analysis, the least absolute shrinkage and selection operator (LASSO). With the stepwise regression analysis, a risk score was constructed based on the expression levels of five genes: Risk score = (−0.7736* CCNB2) + (1.0083* DYNC1LI1) + (−0.6755* KIF11) + (0.9588* SPC25) + (1.5237* KIF18A), which can be applied as a signature for predicting the prognosis of HCC patients. The prediction capacity of the risk score for overall survival was validated with both TCGA and ICGC cohorts. The 1-, 3- and 5-year ROC curves were plotted, in which the AUC was 0.842, 0.726 and 0.699 in TCGA cohort and 0.734, 0.691 and 0.700 in ICGC cohort, respectively. Moreover, the expression levels of the five genes were determined in clinical tumor and normal specimens with immunohistochemistry. The novel signature has exhibited good prediction efficacy for the overall survival of HCC patients.

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Horizons of development of immunotherapy for malignant liver tumors

Experimental and Clinical Gastroenterology ◽

10.31146/1682-8658-ecg-191-7-81-89 ◽

2021 ◽

pp. 81-89

Author(s):

V. E. Mukhin ◽

Yu. S. Konstantinova ◽

R. R. Gimadiev ◽

N. V. Mazurchik

Keyword(s):

Liver Tumors ◽

Surgical Excision ◽

Malignant Neoplasms ◽

Therapeutic Approaches ◽

Liver Malignancies ◽

Primary Liver Tumors ◽

Malignant Liver Tumors ◽

Malignant Liver ◽

Methods Of Treatment ◽

New Strategies

Primary liver tumors are one of the most common types of malignant neoplasms. Surgical excision is still the most effective treatment in the early stages of the disease, however in most cases early diagnosis is difficult. Moreover, even if the treatment is carried out according to a radical program, the risk of relapse remains extremely high. In this regard, the search for new strategies for the treatment of liver malignancies that differ from traditional methods of treatment is not terminated. One of such promising approaches is immunotherapy. The present review is devoted to the current understanding of the mechanisms of action and the available clinical experience in the use of immunotherapy approaches in the treatment of liver malignancies. Combining different types of immunotherapy or combining immunotherapy with traditional therapeutic approaches can facilitate a synergistic effect and contribute to the development of personalized medicine.

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