scholarly journals Shift in VEGFA isoform balance towards more angiogenic variants is associated with tumor stage and differentiation of human hepatocellular carcinoma

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4915 ◽  
Author(s):  
Mikhail S. Chesnokov ◽  
Polina A. Khesina ◽  
Darya A. Shavochkina ◽  
Inna F. Kustova ◽  
Leonid M. Dyakov ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Stage ◽  
Clinicopathological Characteristics ◽  
Malignant Liver Tumor ◽  
Tissue Samples ◽  
Advanced Tumor ◽  
Tumor Stages ◽  
Isoform Expression ◽  
Malignant Liver ◽  
Endothelial Growth Factor

Background Hepatocellular carcinoma (HCC) is the most common and aggressive type of malignant liver tumor. HCC progression depends significantly on its vascularization and formation of new blood vessels. Vascular endothelial growth factor A (VEGFA) is a crucial regulator of tumor vascularization and components of VEGF-induced cell signaling pathways are important targets of therapeutical drugs that demonstrated the highest efficiency in case of advanced HCC (sorafenib and regorafenib). VEGFA is expressed as a set of isoforms with different functional properties, thus VEGFA isoform expression pattern may affect tumor sensitivity to anti-angiogenic drugs. However, information about VEGFA isoforms expression in HCC is still incomplete and contradictory. The present study aims to quantitatively investigate VEGFA isoform expression aberrations in HCC tissue. Methods A total of 50 pairs of HCC and non-tumor tissue samples were used to evaluate the VEGFA isoform spectrum using RT-PCR and quantitatively estimate changes in isoform expression using RT-qPCR. Correlations between these changes and tumor clinicopathological characteristics were analyzed. Results We identified VEGFA-189, VEGFA-165, and VEGFA-121 as predominant isoforms in liver tissue. Anti-angiogenic VEGFA-xxxb variants constituted no more than 5% of all mature VEGFA transcripts detected and their expression was not changed significantly in HCC tissue. We demonstrated for the first time that the least active variant VEGFA-189 is frequently repressed in HCC (p < 0.001), while no uniform changes were detected for potent angiogenesis stimulators VEGFA-165 and VEGFA-121. Isoform balance in HCC shifts from VEGFA-189 towards VEGFA-165 or VEGFA-121 in the majority of cases (p < 0.001). Changes in fractions, but not expression levels, of VEGFA-189 (decrease) and VEGFA-121 (increase) correlated with advanced Tumor-Node-Metastasis (TNM) and Barcelona Clinic Liver Cancer (BCLC) tumor stages (p < 0.05), VEGFA-189 fraction reduction was also associated with poor tumor differentiation (p < 0.05). Discussion A distinct shift in VEGFA isoform balance towards more pro-angiogenic variants occurs in HCC tissue and may modulate overall impact of VEGFA signaling. We suppose that the ratio between VEGFA isoforms is an important parameter governing HCC angiogenesis that may affect HCC progression and be used for optimizing the strategy of HCC therapy by predicting the response to anti-angiogenic drugs.

scholarly journals Expression and clinical significance of miR-3615 in hepatocellular carcinoma

2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098154
Author(s):  
Xin Yuan ◽  
Yize Zhang ◽  
Zujiang Yu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Survival Curve ◽  
Clinicopathological Characteristics ◽  
The Cancer Genome Atlas ◽  
Prognostic Information ◽  
Ki 67 ◽  
Tissue Samples ◽  
Expression Levels ◽  
Kaplan Meier ◽  
Serum Alpha Fetoprotein

Objective To investigate the association between microRNA-3615 (miR-3615) expression and the prognosis and clinicopathological features in patients with hepatocellular carcinoma (HCC). Methods We obtained clinicopathological and genomic data and prognostic information on HCC patients from The Cancer Genome Atlas (TCGA) database. We then analyzed differences in miR-3615 expression levels between HCC and adjacent tissues using SPSS software, and examined the relationships between miR-3615 expression levels and clinicopathological characteristics. We also explored the influence of miR-3615 expression levels on the prognosis of HCC patients using Kaplan–Meier survival curve analysis. Results Based on data for 345 HCC and 50 adjacent normal tissue samples, expression levels of miR-3615 were significantly higher in HCC tissues compared with adjacent tissues. MiR-3615 expression levels in HCC patients were negatively correlated with overall survival time and positively correlated with high TNM stage, serum Ki-67 expression level, and serum alpha-fetoprotein level. There were no significant correlations between miR-3615 expression and age, sex, and pathological grade. Conclusion MiR-3615 may be a promising new biomarker and prognostic factor for HCC.

scholarly journals Type III TGF-β Receptor Down-Regulation Promoted Tumor Progression via Complement Component C5a Induction in Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1503
Author(s):  
Oscar Wai Ho Yeung ◽  
Xiang Qi ◽  
Li Pang ◽  
Hui Liu ◽  
Kevin Tak Pan Ng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Progression ◽  
Tumor Stage ◽  
Complement Component ◽  
Soluble Form ◽  
Advanced Tumor Stage ◽  
Down Regulation ◽  
Type Iii ◽  
Advanced Tumor ◽  
Β Receptor

Background and Aims—Transforming growth factor-beta (TGF-β) signaling orchestrates tumorigenesis and one of the family members, TGF-β receptor type III (TGFβR3), are distinctively under-expressed in numerous malignancies. Currently, the clinical impact of TGFβR3 down-regulation and the underlying mechanism remains unclear in hepatocellular carcinoma (HCC). Here, we aimed to identify the tumor-promoting roles of decreased TGFβR3 expression in HCC progression. Materials and Methods—For clinical analysis, plasma and liver specimens were collected from 100 HCC patients who underwent curative resection for the quantification of TGFβR3 by q-PCR and ELISA. To study the tumor-promoting mechanism of TGFβR3 downregulation, HCC mouse models and TGFβR3 knockout cell lines were applied. Results—Significant downregulation of TGFβR3 and its soluble form (sTGFβR3) were found in HCC tissues and plasma compared to healthy individuals (p < 0.01). Patients with <9.4 ng/mL sTGFβR3 exhibited advanced tumor stage, higher recurrence rate and shorter disease-free survival (p < 0.05). The tumor-suppressive function of sTGFβR3 was further revealed in an orthotopic mouse HCC model, resulting in 2-fold tumor volume reduction. In TGFβR3 knockout hepatocyte and HCC cells, increased complement component C5a was observed and strongly correlated with shorter survival and advanced tumor stage (p < 0.01). Interestingly, C5a activated the tumor-promoting Th-17 response in tumor associated macrophages. Conclusion—TGFβR3 suppressed tumor progression, and decreased expression resulted in poor prognosis in HCC patients through upregulation of tumor-promoting complement C5a.

Alpha-fetoprotein production by non-hepatocellular carcinoma, malignant liver tumor

2009 ◽  
Vol 46 (3) ◽  
pp. 253 ◽  
Author(s):  
SK Sarin ◽  
V Saini ◽  
K Madan ◽  
VV Mittal ◽  
P Sakhuja
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Tumor ◽  
Alpha Fetoprotein ◽  
Malignant Liver Tumor ◽  
Malignant Liver

scholarly journals Heterogeneous Periostin Expression in Different Histological Variants of Papillary Thyroid Carcinoma

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Simona Eliza Giusca ◽  
Cornelia Amalinei ◽  
Ludmila Lozneanu ◽  
Delia Ciobanu Apostol ◽  
Elena Corina Andriescu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tumor Stage ◽  
Clinicopathological Characteristics ◽  
Advanced Tumor Stage ◽  
Histological Subtypes ◽  
Tumor Pathology ◽  
Advanced Tumor ◽  
Histological Variants ◽  
Tall Cell

Background. Periostin (PN) epithelial and stromal overexpression in tumor pathology has been studied according to tumor growth, angiogenesis, invasiveness, and metastasis, but a limited number of studies address PN in thyroid tumors. Aim. Our study aimed to analyze PN expression in different histological variants of PTC and to correlate its expression with the clinicopathological prognostic factors. Material and Methods. PN expression has been immunohistochemically assessed in 50 cases of PTC (conventional, follicular, oncocytic, macrofollicular, and tall cell variants), in tumor epithelial cells and intratumoral stroma. The association between PN expression and clinicopathological characteristics has been evaluated. Results. Our results show that PTC presented different patterns of PN immunoreaction, stromal PN being significantly associated with advanced tumor stage and extrathyroidal extension. No correlations were found between PN overexpression in tumor epithelial cells and clinicopathological features, except for specific histological variants, the highest risk of poor outcome being registered for the conventional subtype in comparison to the oncocytic type. Conclusions. Our study demonstrates differences in PN expression in histological subtypes of PTC. Our results plead in favor of a dominant protumorigenic role of stromal PN, while the action of epithelial PN is less noticeable.

scholarly journals Multi-Omic Analyses of the m5C Regulator ALYREF Reveal Its Essential Roles in Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Chen Xue ◽  
Yalei Zhao ◽  
Ganglei Li ◽  
Lanjuan Li
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Immune Cell ◽  
The Cancer Genome Atlas ◽  
Cancer Tissue ◽  
Hub Genes ◽  
Specific Expression ◽  
Tissue Samples ◽  
Expression Levels ◽  
Advanced Tumor

The ALYREF protein acts as a crucial epigenetic regulator in several cancers. However, the specific expression levels and functional roles of ALYREF in cancers are largely unknown, including for hepatocellular carcinoma (HCC). In a pan-cancer tissue analysis that included HCC, we assessed the expression of ALYREF compared to normal tissues using The Cancer Genome Atlas database. Associations between ALYREF gene expression and the clinical characteristics of HCC patient samples were assessed using the UALCAN database. Kaplan-Meier plots were performed to assess HCC patient prognosis, and the TIMER database was used to explore associations between ALYREF expression and immune-cell infiltrations. The same methods were used to assess eIF4A3 expression in HCC patient samples. In addition, ALYREF- and elF4A3-related differentially expressed genes (DEGs) were determined using LinkedOmics, associated protein functionalities were predicted for positively associated DEGs, and both the TargetScan and miRDB databases were used to predict potential upstream miRNAs for control of ALYREF and eIF4A3 expression. We found that ALYREF gene expression was dysregulated in several cancers and was significantly elevated in HCC patient tissue samples and HCC cell lines. The overexpression of ALYREF was significantly related to both advanced tumor-node-metastasis stages and poor HCC prognosis. Furthermore, we found that eIF4A3 expression was significantly correlated with ALYREF expression, and that upregulated eIF4A3 was significantly associated with poor HCC patient outcomes. In the protein-protein interaction network, we identified eight hub genes based on the positively associated DEGs in common between ALYREF and eIF4A3, and the high expression levels of these hub genes were positively associated with patient clinical outcomes. In addition, we identified miR-4666a-5p and miR-6124 as potential regulators of ALYREF and eIF4A3 expression. These findings suggest that increased ALYREF expression may function as a novel biomarker for both HCC diagnosis and prognosis predictions.

scholarly journals Liprin-β1 is upregulated in human hepatocellular carcinoma and is associated with advanced tumor stage

2019 ◽  
Vol 71 (3) ◽  
pp. 469-474
Author(s):  
Xinying Li ◽  
Jingmei Li ◽  
Jiao Yang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Stage ◽  
Tumor Stage ◽  
Human Hepatocellular Carcinoma ◽  
Advanced Tumor Stage ◽  
Advanced Clinical Stage ◽  
Advanced Tumor ◽  
Elevated Expression ◽  
Clinicopathological Significance ◽  
Liver Tissues

Liprin-?1 is one of the broadly-expressed liprin family members. Dysregulation of liprin-?1 has been implicated in several types of human cancers. However, the expression of liprin-?1 and its clinicopathological significance in human hepatocellular carcinoma (HCC) remains elusive. We evaluated the protein expression of liprin-?1 in HCC and non-tumor liver tissues by immunohistochemistry, and investigated the relationship between liprin-?1 expression and the clinicopathological attributes of HCC. We found that liprin-?1 expression was significantly higher in HCC than in non-tumor liver tissues. Further analysis showed that higher levels of liprin-?1 in HCC were significantly associated with the advanced clinical stage. Interestingly, liprin-?1 was not detected in cholangiocellular carcinoma specimens. These findings suggest that an elevated expression of liprin-?1 may be involved in HCC progression, providing the rationale that upregulation of liprin-?1 may serve as a novel biomarker for human HCC.

TRIB3 promotes hepatocellular carcinoma growth and predicts poor prognosis

2020 ◽  
Vol 29 (3) ◽  
pp. 307-315
Author(s):  
Xiao-Jun Wang ◽  
Fei-Fei Li ◽  
Yi-Jing Zhang ◽  
Man Jiang ◽  
Wan-Hua Ren
Keyword(s):  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Xenograft Model ◽  
Clinicopathological Characteristics ◽  
Tissue Samples ◽  
Normal Tissues ◽  
Related Family ◽  
Hcc Cells

BACKGROUND: Tribbles pseudokinase 3 (TRIB3) is a member of the tribbles-related family, which is involved a lot of cellular processes and multiple cancers, such as breast cancer, colorectal cancer, renal cell carcinomas, and lung cancer. However, the expression pattern and biological function of TRIB3 in hepatocellular carcinoma (HCC) has not yet been completely elucidated. METHODS: The expression of TRIB3 and clinicopathological characteristics were evaluated by HCC tissue microarray and qPCR analysis. Lentivirus packaging and transfection were employed to establish cell lines with TRIB3 overexpression or knockdown. The biological functions of TRIB3 in the growth of HCC were determined using MTT and crystal violet assays. Tumor growth was monitored in a xenograft model in vivo. RESULTS: The expression of TRIB3 was upregulated in HCC tissue samples compared to paired normal tissues in 45 patients examined by qPCR assay. TRIB3 expression was significantly correlated with HCC tumor size and prognosis in postoperative patients by analysis of the TRIB3 expression data and HCC clinical features. Forced expression of TRIB3 significantly promoted HCC growth in vitro. In contrast, downregulation of TRIB3 inhibited cell growth in vitro. Moreover, knockdown of TRIB3 suppressed tumorigenesis of HCC cells in vivo. CONCLUSION: TRIB3 promotes growth abilities of HCC cells both in vitro and in vivo and predicts poor prognosis of HCC patients, which serves as a prognostic marker and might provide a potential therapeutic candidate for patients with HCC.

scholarly journals Thymosin β 10 is overexpressed and associated with unfavorable prognosis in hepatocellular carcinoma

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Chunrong Song ◽  
Zhong Su ◽  
Jing Guo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Human Cancer ◽  
Normal Liver ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Tumor Biomarker ◽  
Advanced Tumor Stage ◽  
Poor Overall Survival ◽  
Tissue Samples ◽  
Advanced Tumor

Abstract Thymosin β 10 (TMSB10) has been demonstrated to be overexpressed and function as an oncogene in most types of human cancer including hepatocellular carcinoma (HCC). In our study, we present more evidence about the clinical significance and biological function of TMSB10 in HCC. First, we observed levels of TMSB10 expression were obviously increased in HCC tissues compared with normal liver tissues at The Cancer Genome Atlas (TCGA) datasets. Furthermore, we confirmed that TMSB10 mRNA and protein levels were also increased in HCC tissue samples compared with normal adjacent normal liver tissue samples. In addition, we found high TMSB10 expression was remarkably associated with the advanced tumor stage, large tumor size, distant metastasis, and poor prognosis, and acted as an independent factor for predicting poor overall survival in HCC patients. Loss-of-function studies suggested silencing of TMSB10 expression dramatically reduced cell proliferation, migration, and invasion in HCC. In conclusion, TMSB10 may hold promise as a tumor biomarker for predicting prognosis and a potential target for developing a novel therapeutic strategy.

scholarly journals Clusterin role in hepatocellular carcinoma patients treated with oxaliplatin

2020 ◽  
Vol 40 (2) ◽  
Author(s):  
Xiumei Wang ◽  
Yongqiang Liu ◽  
Qiong Qin ◽  
Ti Zheng
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Prognostic Value ◽  
Cox Regression ◽  
Poor Response ◽  
Prognostic Indicator ◽  
Tumor Stage ◽  
Chi Square ◽  
Tissue Samples ◽  
Cox Regression Analysis

Abstract Aim: To explore the prognostic value of clusterin (CLU) in hepatocellular carcinoma (HCC) patients treated with oxaliplatin (OXA). Methods: Relative expression of plasma CLU mRNA was examined via fluorescence quantitative real-time PCR (qRT-PCR), and CLU protein level in tissue samples was detected through immunohistochemistry. Chi-square test was used to analyze the relationship between CLU mRNA expression and clinical features of HCC patients treated with OXA. Kaplan–Meier method was performed to assess overall survival for the patients, and prognostic value of CLU in HCC patients was estimated via Cox regression analysis. Results: CLU expression in plasma and tissue specimens was significantly higher among HCC patients than in non-malignant controls (P &lt; 0.001 for both). Moreover, elevated CLU mRNA was closely related to tumor stage, lymph node metastasis and response to OXA (P &lt; 0.05). HCC patients with high CLU expression showed poor response to OXA. In addition, low CLU levels predicted long overall survival time among the study subjects (20.8 vs. 36.6 months, P &lt; 0.001). CLU was an independent prognostic indicator for HCC patients treated with OXA (HR = 2.587, 95%CI = 1.749–3.828, P &lt; 0.001). Conclusion: CLU may be a novel prognostic marker for HCC patients treated with OXA.

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