scholarly journals Associations Between DPP9 Expression, Survival and Gene Expression Signature in Human Hepatocellular Carcinoma: Comprehensive In Silico Analyses

2021 ◽  
Author(s):  
Jiali Carrie Huang ◽  
Abdullah Al Emran ◽  
Justine Moreno Endaya ◽  
Geoffrey W McCaughan ◽  
Mark D Gorrell ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gene Expression Signature ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Nucleotide Polymorphisms ◽  
Loss Of Function ◽  
Poor Survival ◽  
Liver Tumours ◽  
Genomic Databases ◽  
Cancer Pathogenesis

Dipeptidyl peptidase (DPP) 9, DPP8, DPP4 and fibroblast activation protein (FAP) are the four enzymatically active members of the S9b protease family. Associations of DPP9 with human liver cancer, exonic single nucleotide polymorphisms (SNPs) in DPP9 and loss of function (LoF) variants have not been explored. Human genomic databases including The Cancer Genome Atlas (TCGA) were interrogated to identify DPP9 LoF variants and associated cancers. Survival and gene signature analyses were performed on hepatocellular carcinoma (HCC) data. We found that DPP9 and DPP8 are intolerant to LoF variants. DPP9 LoF variants were most often associated with uterine carcinoma. Two DPP9 intronic SNPs that have been associated with lung fibrosis and COVID-19 were not associated with liver fibrosis or cancer. All four DPP4-like genes were overexpressed in liver tumours and their joint high expression was associated with poor survival in HCC. Increased DPP9 expression was associated with obesity in HCC patients.. High expression of genes that positively correlated with overexpression of DPP4, DPP8, and DPP9 were associated with very poor survival in HCC. Enriched pathways analysis of these positively correlated genes featured Toll-like receptor and SUMOylation pathways. This comprehensive data mining suggests that DPP9 is essential for human survival and the DPP4 protease family is important in cancer pathogenesis.

scholarly journals DPP9: Comprehensive In Silico Analyses of Loss of Function Gene Variants and Associated Gene Expression Signatures in Human Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1637
Author(s):  
Jiali Carrie Huang ◽  
Abdullah Al Emran ◽  
Justine Moreno Endaya ◽  
Geoffrey W. McCaughan ◽  
Mark D. Gorrell ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Tumors ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Nucleotide Polymorphisms ◽  
Loss Of Function ◽  
Poor Survival ◽  
Genomic Databases ◽  
Family Associations

Dipeptidyl peptidase (DPP) 9, DPP8, DPP4 and fibroblast activation protein (FAP) are the four enzymatically active members of the S9b protease family. Associations of DPP9 with human liver cancer, exonic single nucleotide polymorphisms (SNPs) in DPP9 and loss of function (LoF) variants have not been explored. Human genomic databases, including The Cancer Genome Atlas (TCGA), were interrogated to identify DPP9 LoF variants and associated cancers. Survival and gene signature analyses were performed on hepatocellular carcinoma (HCC) data. We found that DPP9 and DPP8 are intolerant to LoF variants. DPP9 exonic LoF variants were most often associated with uterine carcinoma and lung carcinoma. All four DPP4-like genes were overexpressed in liver tumors and their joint high expression was associated with poor survival in HCC. Increased DPP9 expression was associated with obesity in HCC patients. High expression of genes that positively correlated with overexpression of DPP4, DPP8, and DPP9 were associated with very poor survival in HCC. Enriched pathways analysis of these positively correlated genes featured Toll-like receptor and SUMOylation pathways. This comprehensive data mining suggests that DPP9 is important for survival and that the DPP4 protease family, particularly DPP9, is important in the pathogenesis of human HCC.

scholarly journals DDX23 is a Metabolic Regulator in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Jianlong Zhou ◽  
Xiaoming Wang ◽  
Jing Liang ◽  
Chaohui Tan ◽  
Changnan Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Rna Sequencing ◽  
High Expression ◽  
Rna Seq ◽  
Loss Of Function ◽  
Rna Helicases ◽  
Poor Survival ◽  
Hcc Cells

Abstract Background: Although biochemical activities of RNA helicases have been well-studied, physiological meaning of those factors in both normal and disease condition remained to be clarified.Methods: RNA sequencing (RNA-seq) in HCC cells indicated DDX23 are highly expressed in HCC and high expression of DDX23 is responsible for poor survival of HCC patients. Next, The expression of DDX23 was establish for subsequent investigation. The roll of DDX23 in HCC was identified by RNA-seq, RT-qPCR, LC-MS, OCR, ECAR. The effect of DDX23 on proliferative, Cloning information as well as tumorigenicity of transfected cells in mice was examined using loss-of-function experiments.Results: Here, we investigated a new role of RNA helicase in a member of the DEAD box protein family, DDX23 in hepatocellular carcinoma (HCC). RNA level of DDX23 are highly expressed in HCC and high expression of DDX23 is responsible for poor survival of HCC patients. In addition, we demonstrated that DDX23 expression is important for in vitro and in vivo tumorigenesis. RNA sequencing (RNA-seq) in HCC cells indicated that metabolism is the most affected pathway by the DDX23 and most abundant DDX23-interacting RNA are involved in metabolism in HCC, especially glycolysis. Conclusions: These findings provide new insights on the unexpected HCC-related role of DDX23, an opportunities for the development of the therapeutic target which is a master regulator of genes involved in HCC-favorable metabolic reprogram at the RNA level.

scholarly journals Expression and clinical significance of CMTM1 in hepatocellular carcinoma

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 217-223
Author(s):  
Xin Song ◽  
Shidong Zhang ◽  
Run Tian ◽  
Chuanjun Zheng ◽  
Yuge Xu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transmembrane Domain ◽  
Disease Free Survival ◽  
Clinicopathological Characteristics ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Chi Square ◽  
Tumor Tissues ◽  
The Relationship ◽  
Low Expression

Abstract Background CKLF Like Marvel Transmembrane Domain Containing 1 (CMTM1) plays a role in breast cancer and lung cancer, but studies on the occurrence and development of CMTM1 in hepatocellular carcinoma (HCC) have not been reported. Methods The Cancer Genome Atlas (TCGA) database and immunohistochemistry (IHC) were used to detect CMTM1 expression in HCC tissues. The relationship between CMTM1 expression and the clinicopathological characteristics of HCC patients was analyzed by chi-square test, and the relationship between CMTM1 expression and the prognosis of HCC patients was tested by the Kaplan–Meier model. Results Bioinformatics analysis showed that the mRNA expression of CMTM1 was upregulated in HCC tissues, and low expression of CMTM1 is associated with longer disease-free survival in patients with HCC. Similarly, the survival time of HCC patients in CMTM1 high expression group was significantly shorter than that in CMTM1 low expression group. IHC detection indicated that CMTM1 protein was highly expressed in both HCC and adjacent non-tumor tissues, with a positive expression in 84% (63/75) of HCC tissues and 89.3% (67/75) of adjacent non-tumor tissues. Moreover, CMTM1 expression was related to family history and TNM stage of HCC patients (P < 0.05), but had no relationship with other clinicopathological characteristics. The survival analysis based on IHC results showed that the prognosis of HCC patients in CMTM1 negative group was significantly poorer than that in CMTM1 positive group (P < 0.05). Conclusion CMTM1 has a high expression in HCC tissues and is related to the prognosis of HCC patients.

scholarly journals High Expression of ANXA2 Pseudogene ANXA2P2 Promotes an Aggressive Phenotype in Hepatocellular Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Qiu-shuang Wang ◽  
Liang-Liang Shi ◽  
Fei Sun ◽  
Yi-fan Zhang ◽  
Ren-Wang Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Disease Free Survival ◽  
Annexin A2 ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Migration And Invasion ◽  
Targeted Drugs ◽  
Noncancerous Tissue ◽  
Expression Levels ◽  
Hcc Cells

Objective. Accumulating evidence suggests that pseudogenes play potential roles in the regulation of their cognate wild-type genes, oncogenes, and tumor suppressor genes. ANXA2P2 (annexin A2 pseudogene 2) is one of three pseudogenes of annexin A2 that have recently been shown to be aberrantly transcribed in hepatocellular carcinoma (HCC) cells. However, its clinical meaning and biological function in HCC have remained unclear. Therefore, the present study was aimed at exploring the prognostic value of a high expression of ANXA2P2 in HCC tissue and at identifying whether it can affect the efficacy of targeted drugs (sorafenib, regorafenib, and lenvatinib). Methods. We obtained ANXA2P2 mRNA expression levels from The Cancer Genome Atlas (TCGA) RNA sequence database. The expression levels of ANXA2P2 in 49 pairs of intratumoral and peritumoral liver tissues were examined by RT-PCR. Wound healing and transwell assays were performed to confirm the tumor-promoting properties of ANXA2P2 in HCC cells. CCK8 assay was conducted to identify whether ANXA2P2 can affect the growth of HCC cells when administered with targeted drugs (sorafenib, regorafenib, and lenvatinib). Results. The expression of ANXA2P2 in HCC tissues was significantly higher than that in adjacent cancerous tissues from TCGA database and validation group. Additionally, patients with high ANXA2P2 expression in HCC tissue had a shorter overall survival, whereas no statistically significant correlation was found between ANXA2P2 expression and disease-free survival (p=0.08) as well as other clinical parameters, such as age, gender, histological grade, T classification, stage, albumin level, alpha-fetoprotein, and vascular invasion (p=0.7323, 0.8807, 0.5762, 0.8515, 0.7113, 0.242, 1.0000, and 0.7685, respectively). Furthermore, in vitro experiments showed that knockdown of ANXA2P2 inhibited migration and invasion of HCC cells but did not have an influence on the HCC cell proliferation when treated with targeted drugs (sorafenib, regorafenib, and lenvatinib). Conclusion. Our study confirmed elevated ANXA2P2 expression levels in HCC tissue compared with adjacent noncancerous tissue and a worse prognosis of patients with high ANXA2P2 levels in the HCC tissue. The newly found properties of promoting migration and invasion of ANXA2P2 in HCC help to explain this phenomenon. ANXA2P2 could be a novel and suitable predicative biomarker for the risk assessment of recurrence or metastasis of HCC patients but may not be effective to predict the efficacy of targeted drugs.

Upregulation of SGOL2 Predicts Poor Prognosis and Facilitates Hepatocellular Carcinoma Progression via Dysregulating the Cell Cycle by Directly Activating MAD2

2021 ◽  
Author(s):  
Qingqing Hu ◽  
Xiaochu Hu ◽  
Yalei Zhao ◽  
Lingjian Zhang ◽  
Ya Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
The Cancer Genome Atlas ◽  
Loss Of Function ◽  
Protein Levels ◽  
Cancer Genome Atlas ◽  
Centromeric Protein ◽  
Hcc Cells

Abstract Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Shugoshin-like protein 2 (SGOL2) is a centromeric protein that ensures the correct and orderly process of mitosis by protecting and maintaining centripetal adhesions during meiosis and mitosis. However, the role of SGOL2 in cancer is not well understood. Methods: The mRNA and protein levels of SGOL2 and survival analysis were conducted in The Cancer Genome Atlas (TCGA) and further validated in 2 independent cohorts. Differential genes correlated with SGOL2 and mitotic arrest deficient 2 like 1 (MAD2) were obtained using LinkedOmics. Subsequently, loss-of-function and rescue assays were carried out in vitro and in vivo to assess the functions of SGOL2 in hepatic tumorigenisis. Findings: We found that SGOL2 was significantly overexpressed in HCC and predicted unfavorable overall survival in HCC patients. Next, we identified 47 differentially expressed genes positively correlated with both SGOL2 and MAD2 to be mainly involved in the cell cycle. In addition, SGOL2 downregulation suppressed the migration, invasion, proliferation, stemness and EMT of HCC cells and inhibited tumorigenesis in vivo. Furthermore, SGOL2 promoted tumor proliferation by activating MAD2-induced cell cycle dysregulation, which could be reversed by the MAD2 inhibitor M2I-1. We also proved that SGOL2 activated MAD2 by directly binding with MAD2. Conclusions: The results of this study showed that SGOL2 acts as an oncogene in HCC cells by directly activating MAD2 and then dysregulating the cell cycle, thereby providing a potential target for HCC patients in the future.

High expression of Golgi phosphoprotein-3 is associated with poor survival in patients with hepatocellular carcinoma

Tumor Biology ◽  
2014 ◽  
Vol 35 (9) ◽  
pp. 8625-8632 ◽  
Author(s):  
Guang-Sheng Hu ◽  
Ying-Qing Li ◽  
Yu-Ming Yang ◽  
Wei Shi ◽  
Ai-Jun Liao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Expression ◽  
Poor Survival

scholarly journals Letter of Retraction

2015 ◽  
Vol 38 (3) ◽  
pp. 142
Author(s):  
Editor CIM
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Expression ◽  
Poor Survival ◽  
Tumour Biology

It has come to our attention that the a manuscript published in CIM: JianXin J, Cha Y, ZhiPeng L, Jie X, Hao Z, Meiyuan C, ChengYi S “GOLP3 is a predictor of survival in patients with hepatocellular carcinoma” Clin Invest Med. 2014 Aug 1;37(4):E233-42 contains text identical to a manuscript published in Tumour Biology: Hu GS, Li YQ, Yang YM, Shi W, Liao AJ, Yao YH, Zeng B, Yuan J “High expression of Golgi phosphoprotein-3 is associated with poor survival in patients with hepatocellular carcinoma” Tumour Biol. 2014 Sep;35(9):8625-32. doi: 10.1007/s13277-014-2105-8. Epub 2014 May 28. For this reason, the publication in CIM has been retracted. Jonathan Angel, MD
Editor, CIM

scholarly journals Dysregulation of Circadian Clock Genes as Significant Clinic Factor in the Tumorigenesis of Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Youfang Liang ◽  
Shaoxiang Wang ◽  
Xin Huang ◽  
Ruihuan Chai ◽  
Qian Tang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Circadian Clock ◽  
Predictive Accuracy ◽  
Clock Genes ◽  
Close Association ◽  
Therapeutic Targets ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Poor Survival ◽  
Circadian Clock Genes

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality worldwide due to its asymptomatic onset and poor survival rate. This highlights the urgent need for developing novel diagnostic markers for early HCC detection. The circadian clock is important for maintaining cellular homeostasis and is tightly associated with key tumorigenesis-associated molecular events, suggesting the so-called chronotherapy. An analysis of these core circadian genes may lead to the discovery of biological markers signaling the onset of the disease. In this study, the possible functions of 13 core circadian clock genes (CCGs) in HCC were systematically analyzed with the aim of identifying ideal biomarkers and therapeutic targets. Profiles of HCC patients with clinical and gene expression data were downloaded from The Cancer Genome Atlas and International Cancer Genome Consortium. Various bioinformatics methods were used to investigate the roles of circadian clock genes in HCC tumorigenesis. We found that patients with high TIMELESS expression or low CRY2, PER1, and RORA expressions have poor survival. Besides, a prediction model consisting of these four CCGs, the tumor-node-metastasis (TNM) stage, and sex was constructed, demonstrating higher predictive accuracy than the traditional TNM-based model. In addition, pathway analysis showed that these four CCGs are involved in the cell cycle, PI3K/AKT pathway, and fatty acid metabolism. Furthermore, the network of these four CCGs-related coexpressed genes and immune infiltration was analyzed, which revealed the close association with B cells and nTreg cells. Notably, TIMELESS exhibited contrasting effects against CRY2, PER1, and RORA in most situations. In sum, our works revealed that these circadian clock genes TIMELESS, CRY2, PER1, and RORA can serve as potential diagnostic and prognostic biomarkers, as well as therapeutic targets, for HCC patients, which may promote HCC chronotherapy by rhythmically regulating drug sensitivity and key cellular signaling pathways.

scholarly journals Analysis and Validation of circRNA-miRNA Network in Regulating m6A RNA Methylation Modulators Reveals CircMAP2K4/miR-139-5p/YTHDF1 Axis Involving the Proliferation of Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Fanwu Chi ◽  
Yong Cao ◽  
Yuhan Chen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regulatory Network ◽  
Excision Repair ◽  
Circular Rna ◽  
Gene Expression Omnibus ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Mechanism Study ◽  
Rna Methylation

The m6A RNA methylation modulators play a crucial role in regulating hepatocellular carcinoma (HCC) progression. The circular RNA (circRNA) regulatory network in regulating m6A RNA methylation modulators in HCC remains largely unknown. In this study, 5 prognostic m6A RNA methylation modulators in HCC were identified from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) projects. The differentially expressed microRNAs (DEmiRNAs) and circRNAs (DEcircRNAs) between paired tumor and normal tissues were screened out from TCGA and or Gene Expression Omnibus (GEO) database to construct the circRNA-miRNA- m6A RNA methylation modulator regulatory network, which included three m6A RNA methylation modulators (HNRNPC, YTHDF1, and YTHDF2), 11 DEmiRNAs, and eight DEcircRNAs. Among the network, hsa-miR-139-5p expression was negatively correlated with YTHDF1. Hsa-miR-139-5p low or YTHDF1 high expression was correlated with high pathological grade, advanced stage and poor survival of HCC. Additionally, cell cycle, base excision repair, and homologous recombination were enriched in YTHDF1 high expression group by GSEA. A hub circRNA regulatory network was constructed based on hsa-miR-139-5p/YTHDF1 axis. Furthermore, hsa_circ_0007456(circMAP2K4) was validated to promote HCC cell proliferation by binding with hsa-miR-139-5p to promote YTHDF1 expression. Taken together, we identified certain circRNA regulatory network related to m6A RNA methylation modulators and provided clues for mechanism study and therapeutic targets for HCC.

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