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

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.

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

Frontiers in Oncology ◽

10.3389/fonc.2021.633415 ◽

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.

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MIR100HG: a credible prognostic biomarker and an oncogenic lncRNA in gastric cancer

Bioscience Reports ◽

10.1042/bsr20190171 ◽

2019 ◽

Vol 39 (4) ◽

Cited By ~ 6

Author(s):

Jun Li ◽

Qingfeng Xu ◽

Wen Wang ◽

Shaojun Sun

Keyword(s):

Gastric Cancer ◽

Cancer Patients ◽

Prognostic Biomarker ◽

Human Cancer ◽

The Cancer Genome Atlas ◽

Migration And Invasion ◽

Epithelial Cell Line ◽

Tissue Samples ◽

Poor Prognostic Factor ◽

Gastric Cancer Patients

Abstract The MIR100HG expression was observed to be up-regulated or down-regulated in human cancer tissues depending on tumor types. However, there was no report about the role of MIR100HG in gastric cancer. In our study, we first found levels of MIR100HG expression were increased in gastric cancer cell lines and tissue samples compared with normal gastric epithelial cell line and adjacent normal gastric mucosa tissue samples, respectively. Moreover, high MIR100HG expression was positively associated with clinical stage, tumor invasion, lymph node metastasis, and distant metastasis in gastric cancer patients. Survival analysis showed MIR100HG expression was negative correlated with clinical outcome in gastric cancer patients from The Cancer Genome Atlas (TCGA) database or our study, and high MIR100HG expression served as an independent poor prognostic factor for gastric cancer patient’s overall survival. The study in vitro suggested down-regulation of MIR100HG expression inhibits cell proliferation, migration, and invasion in gastric cancer. In conclusion, MIR100HG is a credible prognostic biomarker and functions as an oncogenic lncRNA in gastric cancer.

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Identification of Prognostic Biomarkers and Independent Indicators Among PFDN1/2/3/4/5/6 in Liver Hepatocellular Carcinoma

10.21203/rs.3.rs-725619/v1 ◽

2021 ◽

Author(s):

Yin-Hai Dai ◽

Fuping Li ◽

Wei-Jie Kong ◽

Xue-Qin Zhang ◽

Mao Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

T Cells ◽

Human Cancer ◽

Normal Liver ◽

The Cancer Genome Atlas ◽

Prognostic Biomarkers ◽

Expression Levels ◽

Kaplan Meier ◽

Human Protein Atlas ◽

Liver Hepatocellular Carcinoma

Abstract Background: Previous studies have proved that the aberrant expressions of PFDNs (Prefoldin) family proteins were correlated with several human cancer. However, the specific functions of PFDNs in liver hepatocellular carcinoma(LIHC) remain unknown. The study aimed to identify the prognostic biomarkers and independent indicators among PFDN1/2/3/4/5/6 in liver hepatocellular carcinoma.Methods: We used these databases including Oncomine, Ualcan, GEPIA2, Human Protein Atlas, The Cancer Genome Atlas, Kaplan-Meier plotter, cBioPortal, STRI-NG and TIMER and the software of Cytoscape in our study.Results: PFDN1/2/3/4/5/6 were highly expressed in LIHC tissues. The mRNA expression levels of PFDN1/2/3/4/5/6 were relevant to tumor grades.PFDN1/3/4/5 expressions significantly changed in different cancer stages. The protein expression levels of PFDNs were higher in LIHC tissue than normal liver tissue. Moreover, High mRNA expressions of PFDN1/2/3/4 were associated with shorter OS of LIHC patients. In multivariate analysis,high expressions of PFDN1/2/4 were independently correlated with poorer OS of LIHC patients. In our findings,55% of patients with LIHC had genetic mutations on PFDNs. Besides, there were significant associations between the expressions of PFDN1/2/3/4/5 and six types of infiltrated immune cells(B cells, CD4+T cells, CD8+T cells, neutrophil, macrophage, and dendritic cells).Conclusions:PFDN1/2/3/4 were potential prognostic markers to suggest poor OS of LIHC patients. In addition, high PFDN1/2/4 expressions were independent prognostic factors in OS for LIHC patients.

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Construction and Validation of a Combined Ferroptosis and Hypoxia Prognostic Signature for Hepatocellular Carcinoma

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.809672 ◽

2021 ◽

Vol 8 ◽

Author(s):

Kai Wen ◽

Yongcong Yan ◽

Juanyi Shi ◽

Lei Hu ◽

Weidong Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cox Regression ◽

Tumor Staging ◽

Tumor Therapy ◽

Normal Liver ◽

Cancer Genome ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Prognostic Signature ◽

Advanced Tumor

Background: Ferroptosis, as a unique programmed cell death modality, has been found to be closely related to the occurrence and development of hepatocellular carcinoma (HCC). Hypoxia signaling pathway has been found to be extensively involved in the transformation and growth of HCC and to inhibit anti-tumor therapy through various approaches. However, there is no high-throughput study to explore the potential link between ferroptosis and hypoxia, as well as their combined effect on the prognosis of HCC.Methods: We included 370 patients in The Cancer Genome Atlas (TCGA) database and 231 patients in the International Cancer Genome Consortium (ICGC) database. Univariate COX regression and Least Absolute Shrinkage and Selection Operator approach were used to construct ferroptosis-related genes (FRGs) and hypoxia-related genes (HRGs) prognostic signature (FHPS). Kaplan–Meier method and Receiver Operating Characteristic curves were analyzed to evaluate the predictive capability of FHPS. CIBERSOR and single-sample Gene Set Enrichment Analysis were used to explore the connection between FHPS and tumor immune microenvironment. Immunohistochemical staining was used to compare the protein expression of prognostic FRGs and HRGs between normal liver tissue and HCC tissue. In addition, the nomogram was established to facilitate the clinical application of FHPS.Results: Ten FRGs and HRGs were used to establish the FHPS. We found consistent results in the TCGA training cohort, as well as in the independent ICGC validation cohort, that patients in the high-FHPS subgroup had advanced tumor staging, shorter survival time, and higher mortality. Moreover, patients in the high-FHPS subgroup showed ferroptosis suppressive, high hypoxia, and immunosuppression status. Finally, the nomogram showed a strong prognostic capability to predict overall survival (OS) for HCC patients.Conclusion: We developed a novel prognostic signature combining ferroptosis and hypoxia to predict OS, ferroptosis, hypoxia, and immune status, which provides a new idea for individualized treatment of HCC patients.

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The rs599839 A>G Variant Disentangles Cardiovascular Risk and Hepatocellular Carcinoma in NAFLD Patients

10.20944/preprints202103.0400.v1 ◽

2021 ◽

Author(s):

Marica Meroni ◽

Miriam Longo ◽

Erika Paolini ◽

Anna Alisi ◽

Luca Miele ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Tumor Stage ◽

The Cancer Genome Atlas ◽

Advanced Tumor Stage ◽

Mrna Levels ◽

Nonalcoholic Fatty Liver ◽

Advanced Tumor

Background and Aims: Dyslipidemia and cardiovascular diseases (CAD) are comorbidities of nonalcoholic fatty liver disease (NAFLD), which ranges from steatosis to hepatocellular carcinoma (HCC). The rs599839 A>G variant, in the CELSR2-PSRC1-SORT1 cluster, has been associated CAD, but its impact on metabolic traits and liver damage in NAFLD has not been investigated yet. Methods: We evaluated the effect of the rs599839 variant in 1426 NAFLD patients (Overall cohort) of whom 131 have HCC (NAFLD-HCC), in 500,000 individuals from the UK Biobank Cohort (UKBBC) and in 366 HCC samples from The Cancer Genome Atlas (TCGA). Hepatic PSRC1, SORT1 and CELSR2 expressions were evaluated by RNAseq (n=125). Results: The rs599839 variant was associated with reduced circulating LDL, carotid intima-media thickness, carotid plaques and hypertension (p<0.05) in NAFLD patients and with protection against dyslipidemia in UKBBC. The G allele was associated with higher risk of HCC and advanced tumor stage (p<0.05) in the Overall cohort. Hepatic PSRC1, SORT1 and CELSR2 expressions were increased in NAFLD patients carrying the rs599839 variant (p<0.0001). SORT1 mRNA levels negatively correlated with circulating lipids and with those of genes involved in lipoprotein turnover (p<0.0001). Conversely, PSRC1 expression was positively related to that of genes implicated in cell proliferation (p<0.0001). In TCGA, PSRC1 over-expression promoted more aggressive HCC development (p<0.05). Conclusions: In sum, the rs599839 A>G variant improves dyslipidemia thus protecting against CAD in NAFLD patients, but as one it might promote HCC development by modulating SORT1 and PSRC1 expressions which impact on lipid metabolism and cell proliferation, respectively

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Knockdown of MUC16 (CA125) Enhances the Migration and Invasion of Hepatocellular Carcinoma Cells

Frontiers in Oncology ◽

10.3389/fonc.2021.667669 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yao Huang ◽

Xiaoyu Huang ◽

Jianxing Zeng ◽

Jun Lin

Keyword(s):

Hepatocellular Carcinoma ◽

Primary Liver Cancer ◽

Huh7 Cell ◽

Medical Problem ◽

Carbohydrate Antigen ◽

The Cancer Genome Atlas ◽

Migration And Invasion ◽

Tumor Biomarker ◽

Carbohydrate Antigen 125 ◽

Huh7 Cells

As an important global medical problem, hepatocellular carcinoma (HCC) has been recognized as the most frequent primary liver cancer and a leading cause of death among patients with cirrhosis. Surveillance of HCC using serum markers aims to reduce the disease-related mortality of HCC. MUC16 (mucin 16, also known as carbohydrate antigen 125, CA125) has been predicted as a tumor biomarker for many cancer types. Based on the high frequency mutation rate in a database from the Cancer Genome Atlas (TCGA), we investigated the effects of MUC16 knockdown and the regulatory profile of MUC16 in HepG2 and Huh7 cell lines. Knockdown of MUC16 was conducted via siRNA transfection, and the proliferation of cells was not affected by CCK8 assay results. Moreover, decreasing the expression of MUC16 enhanced the migration and invasion of cells, as shown by wound healing and transwell assays. Furthermore, RNA-seq was used to investigate the effect of MUC16 knockdown on the gene expression profile of HepG2 and Huh7 cells. Our study demonstrated the significant role of MUC16 in the inhibition of the migration and invasion of HepG2 and Huh7 cells.

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Upregulated LINC01667 Expression Is Correlated With Poor Prognosis in Hepatocellular Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.650173 ◽

2021 ◽

Vol 11 ◽

Author(s):

Kainan Zhang ◽

Hui Liu ◽

Mengsi Yu ◽

Hui Zhao ◽

Ning Yang ◽

...

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

Cancer Progression ◽

The Cancer Genome Atlas ◽

Migration And Invasion ◽

Poor Overall Survival ◽

Expression Levels ◽

Huh7 Cells ◽

Gene Expression Levels

The development of hepatocellular carcinoma (HCC) is a complex pathological process. Long intergenic non–protein-coding RNA 1667 (LINC01667, also known as MGC38584) plays an oncogenic role in several human cancers; however, its functional role in HCC tumorigenesis remains unknown. Here, we first evaluated the gene expression levels of LINC01667 in HCC using data from The Cancer Genome Atlas and Gene Expression Profiling Interactive Analysis (GEPIA) databases. We then elucidated the association between LINC01667 gene expression levels and the survival rates of patients with HCC. We detected the effect of LINC01667 on the malignant phenotypes (cell proliferation, migration, invasion and apoptosis etc.) and the MAPK and PI3K/AKT/mTOR signaling pathways of HepG2, SMMC-7721 and HUH7 cells. We also analyzed the sensitivity of HepG2, SMMC-7721 and HUH7 with different expression levels of LINC01667 to anti-HCC drugs in vitro. Based on data from the aforementioned databases and our experiments in vitro, we found that LINC01667 was overexpressed in HCC, and that patients with high LINC01667 levels had a remarkably poor overall survival rate. In addition, inhibition of LINC01667 expression suppressed the proliferation, migration and invasion of HepG2 and SMMC-7721 cells and promoted their apoptosis in vitro. In contrast, overexpression of LINC01667 promoted the proliferation, migration and invasion of HUH7 cells and suppressed their apoptosis in vitro. ChIRP-seq (chromatin isolation by RNA purification) showed that LINC01667 bound to MEG3, and downregulated the expression of MEG3. In addition, western blotting showed that LINC01667 could activate the NF-κB pathway to promote cancer progression. In conclusion, we report that LINC01667 is an important oncogene in HCC and may be used as a potential diagnostic and prognostic biomarker of HCC.

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The rs599839 A>G Variant Disentangles Cardiovascular Risk and Hepatocellular Carcinoma in NAFLD Patients

Cancers ◽

10.3390/cancers13081783 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1783

Author(s):

Marica Meroni ◽

Miriam Longo ◽

Erika Paolini ◽

Anna Alisi ◽

Luca Miele ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Tumor Stage ◽

The Cancer Genome Atlas ◽

Advanced Tumor Stage ◽

Mrna Levels ◽

Nonalcoholic Fatty Liver ◽

Advanced Tumor

Background and Aims: Dyslipidemia and cardiovascular diseases (CVD) are comorbidities of nonalcoholic fatty liver disease (NAFLD), which ranges from steatosis to hepatocellular carcinoma (HCC). The rs599839 A>G variant, in the CELSR2-PSRC1-SORT1 gene cluster, has been associated CVD, but its impact on metabolic traits and on the severity liver damage in NAFLD has not been investigated yet. Methods: We evaluated the effect of the rs599839 variant in 1426 NAFLD patients (Overall cohort) of whom 131 had HCC (NAFLD-HCC), in 500,000 individuals from the UK Biobank Cohort (UKBBC), and in 366 HCC samples from The Cancer Genome Atlas (TCGA). Hepatic PSRC1, SORT1 and CELSR2 expressions were evaluated by RNAseq (n = 125). Results: The rs599839 variant was associated with reduced circulating LDL, carotid intima-media thickness, carotid plaques and hypertension (p < 0.05) in NAFLD patients and with protection against dyslipidemia in UKBBC. The minor G allele was associated with higher risk of HCC, independently of fibrosis severity (odds ratio (OR): 5.62; 95% c.i. 1.77–17.84, p = 0.003), poor prognosis and advanced tumor stage (p < 0.05) in the overall cohort. Hepatic PSRC1, SORT1 and CELSR2 expressions were increased in NAFLD patients carrying the rs599839 variant (p < 0.0001). SORT1 mRNA levels negatively correlated with circulating lipids and with those of genes involved in lipoprotein turnover (p < 0.0001). Conversely, PSRC1 expression was positively related to that of genes implicated in cell proliferation (p < 0.0001). In TCGA, PSRC1 over-expression promoted more aggressive HCC development (p < 0.05). Conclusions: In sum, the rs599839 A>G variant is associated with protection against dyslipidemia and CVD in NAFLD patients, but as one it might promote HCC development by modulating SORT1 and PSRC1 expressions which impact on lipid metabolism and cell proliferation, respectively.

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Upregulated Seizure-Related 6 Homolog-Like 2 Is a Prognostic Predictor of Hepatocellular Carcinoma

Disease Markers ◽

10.1155/2020/7318703 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Linhe Wang ◽

Xiangchao Ling ◽

Caihui Zhu ◽

Zhiheng Zhang ◽

Ziming Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cancer Progression ◽

Disease Free Survival ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Poor Overall Survival ◽

Tissue Samples ◽

Prognostic Predictor ◽

Qrt Pcr ◽

Cancer Genome Atlas

Seizure-related 6 homolog-like 2 (SEZ6L2), which is localized on the cell surface, has been found to be associated with tumor angiogenesis and lung cancer progression. However, the role of SEZ6L2 in hepatocellular carcinoma (HCC) is still unclear. We obtained data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) to investigate SEZ6L2 expression and regulation in HCC. Then, HCC tissue samples were collected to verify SEZ6L2 by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical staining (IHC). Patient information was collected for survival and prognosis analysis. qRT-PCR, IHC, and bioinformatics analysis showed that the SEZ6L2 protein was highly expressed in HCC samples. Clinical data showed that high SEZ6L2 protein expression was correlated with tumor-node-metastasis (TNM) stages (P=0.046), tumor number (P=0.016), and tumor size (P=0.029). Meanwhile, SEZ6L2 overexpression was closely associated with poor overall survival and disease-free survival in HCC patients. Moreover, SEZ6L2 is an independent prognostic predictor for the survival of HCC patients. This study suggests a significant correlation between SEZ6L2 and HCC, which means that SEZ6L2 may potentially serve as a useful prognostic biomarker for HCC patients.

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HOX Antisense lincRNA HOXA-AS2 Promotes Tumorigenesis of Hepatocellular Carcinoma

Cellular Physiology and Biochemistry ◽

10.1159/000452545 ◽

2016 ◽

Vol 40 (1-2) ◽

pp. 287-296 ◽

Cited By ~ 28

Author(s):

Fuqiang Wang ◽

Huili Yang ◽

Zhigang Deng ◽

Yongjie Su ◽

QinLiang Fang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Biological Function ◽

Human Cancer ◽

Rank Test ◽

Advanced Tumor Stage ◽

Advanced Tumor ◽

Hcc Cells

Background: Recent studies reveal that long non-coding RNAs (LncRNAs) play critical roles in the proliferation and migration of human cancer. Previous report has shown that LncRNA HOXA-AS2 was involved in carcinoma processes. However, the expression and biological function of HOXA-AS2 in hepatocellular carcinoma (HCC) are poorly understood. Methods: Quantitative real-time PCR (qRT-PCR) was performed to detect the expression of HOXA-AS2 in HCC tissues and cell lines. The relation between lncRNA HOXA-AS2 expression and clinicopathological characteristics was assessed by chi-square test. The prognosis was analyzed using Kaplan-Meier method, and compared differences between the two groups by log-rank test. The biological function of HOXA-AS2 on HCC cells were determined both in vitro and in vivo. Results: In the present study, we found that HOXA-AS2 expression was increased in HCC tissues and adjacent normal tissues and high HOXA-AS2 expression was associated with bigger tumor size, advanced tumor stage, and shorter survival time. Knockdown of HOXA-AS2 significantly inhibited HCC cell proliferation and invasion and resulted in an increase of apoptosis. Furthermore, inhibition of HOXA-AS2 in HCC cells significantly repressed tumorigenicity in nude mice. Conclusion: Our results indicated that the inhibition of HOXA-AS2 in HCC cells significantly inhibited cell proliferation in vitro and in vivo, which might provide a potential possibility for targeted therapy of HCC.

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