scholarly journals Comprehensive Analysis of Aldehyde Dehydrogenases (ALDHs) and Its Significant Role in Hepatocellular Carcinoma

Author(s):  
Senbang Yao ◽  
Wenjun Chen ◽  
He Zuo ◽  
Ziran Bi ◽  
Xiuqing Zhang ◽  
...  

AbstractOxidative DNA damage is closely related to the occurrence and progression of cancer. Oxidative stress plays an important role in alcohol-induced hepatocellular carcinoma (HCC). Aldehyde dehydrogenase (ALDH) is a family of enzymes that plays an essential role in the reducing oxidative damage. However, how ALDHs family affects alcohol-related HCC remains obscure. We aimed to explore the correlation between the differential expression of ALDHs in patients with HCC and pathological features, as well as the relationship between ALDHs and prognosis, and finally analyze the possible mechanism of ALDHs in targeted therapy of HCC. The data of HCC were downloaded from The Cancer Genome Atlas (TCGA) database. This research explored the expression and prognostic values of ALDHs in HCC using Oncomine, UALCAN, Human Protein Atlas, cBioPortal, Kaplan–Meier plotter, GeneMANIA, Tumor Immune Estimation Resource, GEPIA databases, and WebGestalt. Low mRNA and protein expressions of ALDHs were found to be significantly associated with tumor grade and clinical cancer stages in HCC patients. In particular, the loss of ALDH expression is more obvious in Asians, and its effect on prognosis is far more significant than that in the White race. Our findings play an important role in the study of prognostic markers and anti-liver cancer therapeutic targets for the members of the ALDHs family, especially in patients with liver cancer in Asia.

2020 ◽  
Author(s):  
Zaixiong Ji ◽  
Jiaqi Li ◽  
Jianbo Wang

Abstract Background: Replication factor C (RFC) is closely related to tumor progression and metastasis. However, the functional significance of RFC2 in hepatocellular carcinoma remains unclear.Materials and methods: In order to solve this problem, the expression of RFC2 in liver cancer patients was analyzed through ONCOMINE, UALCAN, human protein atlas. Survival analysis was conducted using Kaplan-Meier plotter and GEPIA. GO and KEGG enrichment analyses were carried out. The protein-protein interaction (PPI) network was performed through Metascape.Result: The transcription and protein level of RFC2 in HCC were overexpressed, which was significantly related to the clinical individual cancer stage and pathological tumor grade of HCC patients. In addition, in patients with liver cancer, higher RFC2 expression was found to be significantly correlated with shorter OS and DFS. Furthermore, the function of RFC2 in liver cancer was DNA replication, and its main mechanism was the phase transition of the cell cycle.Conclusion: RFC2 might promote the development of liver cancer. It could also be used as a novel biomarker for the prognosis of liver cancer.


2021 ◽  
Author(s):  
Jun Du ◽  
Jinguo Wang

Abstract Background: The expression and molecular mechanism of cysteine rich transmembrane module containing 1 (CYSTM1) in human tumor cells remains unclear. The aim of this study was to determine whether CYSTM1 could be used as a potential prognostic biomarker for hepatocellular carcinoma (HCC).Methods: We first demonstrated the relationship between CYSTM1 expression and HCC in various public databases. Secondly, Kaplan–Meier analysis and Cox proportional hazard regression model were performed to evaluate the relationship between the expression of CYSTM1 and the survival of HCC patients which data was downloaded in the cancer genome atlas (TCGA) database. Finally, we used the expression data of CYSTM1 in TCGA database to predict CYSTM1-related signaling pathways through bioinformatics analysis.Results: The expression level of CYSTM1 in HCC tissues was significantly correlated with T stage (p = 0.039). In addition, Kaplan–Meier analysis showed that the expression of CYSTM1 was significantly associated with poor prognosis in patients with early-stage HCC (p = 0.003). Multivariate analysis indicated that CYSTM1 is a potential predictor of poor prognosis in HCC patients (p = 0.036). The results of biosynthesis analysis demonstrated that the data set of CYSTM1 high expression was mainly enriched in neurodegeneration and oxidative phosphorylation pathways.Conclusion: CYSTM1 is an effective biomarker for the prognosis of patients with early-stage HCC and may play a key role in the occurrence and progression of HCC.


2020 ◽  
Author(s):  
Xuehui Peng ◽  
Yonggang He ◽  
Xiaobing Huang ◽  
Nan You ◽  
Huiying Gu ◽  
...  

Abstract Background: The tumorigenesis and development of hepatocellular carcinoma (HCC) is a process involving multiple factors. The COMMDs family proteins were reported to play important roles in various disease and cancers including HCC. We previously found COMMD7 acted as a HCC-promotion factor; however, further understanding on COMMD7 was needed. We conducted these bioinformatics analysis for the purpose of comprehensive understanding of the functional role of COMMD7 in HCC.Methods: The bioinformatics analysis of COMMD7 were launched by online platforms including KEGG, GEPIA, cBioportal, Gene Ontology and The Kaplan-Meier plotter. Data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were downloaded, and the data analysis and processing were conducted by RStudio (version 1.3.959) software.Results: The expression profile results of COMMD7 in TCGA and GTEx database suggested that COMMD7 expressed highly in liver tumor tissues and positively related with poorer prognosis (p<0.01); COMMD7 also contributed to the early development of HCC as its higher expression resulted in progression from stage I to stage III (p<0.01). Based on our previous studies, COMMD7 may target NF-κB signaling and CXCL10 to enhance the proliferation of hepatoma cells so that promoting the development of HCC. Conclusions:This study updates the current studies about the newly recognized roles of COMMD7 in the progression of HCC, summarizing the research progress and prospects of COMMD7 comprehensively, offering an outlook for the future investigation and targeted therapy of HCC.


2021 ◽  
Author(s):  
Mingjie Li ◽  
Qianyun Wang ◽  
Qinqin Zheng ◽  
Lin Wu ◽  
Bin Zhao ◽  
...  

Aim: We aimed to evaluate the diagnostic and prognostic values of P4HAs in breast cancer (BC) patients. Materials & methods: Kaplan–Meier plotter was used to evaluate the prognostic values of P4HAs and correlations between their expression and clinical characteristics were assessed based on The Cancer Genome Atlas and the Human Protein Atlas. Results: The current study showed that P4HAs were highly expressed in BC patients with clinical stage I compared with nontumor control and elevated P4HAs were correlated with poor survival outcomes. Subtypes analysis revealed that P4HA1 and P4HA2 were most expressed in HER2+ subtypes patients. Univariate analysis displayed that elevated P4HA1 and P4HA3 correlated with unfavorable recurrence-free survival in mutated TP53 patients. Conclusion: This study indicated the diagnostic and prognostic roles of P4HAs members and broadened the biomarker fields of early diagnosis and prognostic monitoring of BC patients.


2020 ◽  
Author(s):  
Jing Li ◽  
Xuehui Peng ◽  
Yonggang He ◽  
Xiaobing Huang ◽  
Nan You ◽  
...  

Abstract Background: The tumorigenesis and development of hepatocellular carcinoma (HCC) is a process involving multiple factors. The COMMDs family proteins were reported to play important roles in various disease and cancers including HCC. We previously found COMMD7 acted as a HCC-promotion factor; however, further understanding on COMMD7 was needed. We conducted these bioinformatics analysis for the purpose of comprehensive understanding of the functional role of COMMD7 in HCC.Methods: The bioinformatics analysis of COMMD7 were launched by online platforms including KEGG, GEPIA, cBioportal, Gene Ontology and The Kaplan-Meier plotter. Data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were downloaded, and the data analysis and processing were conducted by RStudio (version 1.3.959) software.Results: The expression profile results of COMMD7 in TCGA and GTEx database suggested that COMMD7 expressed highly in liver tumor tissues and positively related with poorer prognosis (p<0.01); COMMD7 also contributed to the early development of HCC as its higher expression resulted in progression from stage I to stage III (p<0.01). Based on our previous studies, COMMD7 may target NF-κB signaling and CXCL10 to enhance the proliferation of hepatoma cells so that promoting the development of HCC. Conclusions:This study updates the current studies about the newly recognized roles of COMMD7 in the progression of HCC, summarizing the research progress and prospects of COMMD7 comprehensively, offering an outlook for the future investigation and targeted therapy of HCC.


2021 ◽  
Author(s):  
Yaguang Fan ◽  
Yingrui Zhu

Abstract Ovarian serous cystadenocarcinoma (OV) is a malignant tumor that often has a poor prognosis because of its late detection. The expression of PTPN2 is associated with a variety of tumors, but its effect on OV is not well understood. Therefore, we analyzed the relationship between PTPN2 and the prognosis of OV. Analysis of patients with OV using The Cancer Genome Atlas revealed an association between PTPN2 expression and the prognosis of OV. We established a model of the relationship between these factors by logistic regression, which showed a significant correlation between the tumor grade and decreased expression of PTPN2. Kaplan-Meier survival analysis showed that low PTPN2 expression was associated with poor overall survival. Further analysis of the expression of immune cells in OV using the ssGSEA package revealed a significant correlation between the expression level of PTPN2 in OV and the numbers of mast, gamma delta, helper, and central memory T cells. We also found differences between the phenotypic pathways associated with low PTPN2 expression and pathways of genes and proteins that determine epithelial-mesenchymal transformation. Finally, a network diagram of protein molecular interactions was drawn using the STRING database, which showed that PTPN2 was closely related to the signal converter and transcriptional activator family and Janus kinase family. Thus, PTPN2 shows potential for use as a prognostic biomarker in OV and is associated with immune infiltration.


2021 ◽  
Author(s):  
Qian Li ◽  
Yannan Chen ◽  
Li Yang ◽  
Yaguang Fan ◽  
Feiyan Li ◽  
...  

Abstract Ovarian serous cystadenocarcinoma (OV) is a malignant tumor that often has a poor prognosis because of its late detection. The expression of PTPN2 is associated with a variety of tumors, but its effect on OV is not well understood. Therefore, we analyzed the relationship between PTPN2 and the prognosis of OV. Analysis of patients with OV using The Cancer Genome Atlas revealed an association between PTPN2 expression and the prognosis of OV. We established a model of the relationship between these factors by logistic regression, which showed a significant correlation between the tumor grade and decreased expression of PTPN2. Kaplan-Meier survival analysis showed that low PTPN2 expression was associated with poor overall survival. Further analysis of the expression of immune cells in OV using the ssGSEA package revealed a significant correlation between the expression level of PTPN2 in OV and the numbers of mast, gamma delta, helper, and central memory T cells. We also found differences between the phenotypic pathways associated with low PTPN2 expression and pathways of genes and proteins that determine epithelial-mesenchymal transformation. Finally, a network diagram of protein molecular interactions was drawn using the STRING database, which showed that PTPN2 was closely related to the signal converter and transcriptional activator family and Janus kinase family. Thus, PTPN2 shows potential for use as a prognostic biomarker in OV and is associated with immune infiltration.


2021 ◽  
Author(s):  
Jia-Ning Zhang ◽  
Qi fei TAO ◽  
Dong yang Ding ◽  
YUAN YANG ◽  
Wei-Ping Zhou

Abstract Background: CBX3 is a key gene that is involved in immune cell regulation, however, its prognostic values and its correlation with infiltrating lymphocytes in various cancers have not been clearly established. This study aims to investigate the role CBX3 in hepatocellular carcinoma (HCC).Methods: We first reviewed the expression of CBX3 in different cancers and adjacent tissues using oncomine database. Next, the authors focus on the expression of CBX3 in hepatocellular carcinoma. Therefore, the expression of CBX3 in hepatocellular carcinoma were analyzed through UALCAN online analysis website and the Human Protein Atlas (www.proteinatlas.org) website. In addition, we further found that CBX3 can be identified as an effective marker for the prognostic guidance of hepatocellular carcinoma according to the Kaplan-Meier plotter database and the Bioinformatics analysis online websites (www.aclbi.com). Next, we used the Bioinformatics analysis online websites to explore whether the expression level of CBX3 in liver cancer is related to the infiltration of certain immune cells. In addition, we also predicted the correlation between immune checkpoint and CBX3 in liver cancer.Results: The analysis results preliminarily show that CBX3 be expressed abnormally in many cancers, and CBX3 was significantly up-regulated in HCC. The high expression of CBX3 indicated survival outcomes and it showed a huge potential as a effective marker for the prognostic guidance of hepatocellular carcinoma. Furthermore, we found that CBX3 in liver cancer is related to the infiltration of certain immune cells, including CD4+ T cells, macrophages and B cells. In addition, the results showed HAVCR2 is most likely to become an effective immune checkpoint for HCC patients immunotherapy with high CBX3 expression.Conclusions: CBX3 is a potential diagnostic and prognostic marker in HCC and related to the infiltration of certain immune cells. It is expected to become a breakthrough point in immunotherapy in the future.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Mingxing Xu ◽  
Jianliang Xu ◽  
Dun Zhu ◽  
Rishun Su ◽  
Baoding Zhuang ◽  
...  

Abstract Background As the fourth leading cause of cancer-related death in the world, the therapeutic effect and 5-year overall survival of hepatocellular carcinoma (HCC) are not optimistic. Previous researches indicated that the disorder of PRDXs was related to the occurrence and development of cancers. Methods In this study, PRDXs were found in various tumor cell lines by CCLE database analysis. The analysis results of UALCAN, HCCDB and Human Protein Atlas databases showed the expression of PRDXs mRNA and protein in HCC tissues was dysregulated. Besides, UALCAN was used to assess the correlations between PRDXs mRNA as well as methylation levels and clinical characterization. Results High expression of PRDX1 or low expression of PRDX2/3 suggested poor prognosis for HCC patients which was demonstrated by Kaplan–Meier Plotter. The genetic alterations and biological interaction network of PRDXs in HCC samples were obtained from c-Bioportal. In addition, LinkedOmics was employed to analyze PRDXs related differentially expressed genes, and on this basis, enrichment of KEGG pathway and miRNAs targets of PRDXs were conducted. The results indicated that these genes were involved in several canonical pathways and certain amino acid metabolism, some of which may effect on the progression of HCC. Conclusions In conclusion, the disordered expression of some PRDX family members was associated with the prognosis of HCC patients, suggesting that these PRDX family members may become new molecular targets for the treatment and prognosis prediction of HCC.


2021 ◽  
Author(s):  
Junwei Zou ◽  
Yong Huang ◽  
Zhaoying Wu ◽  
Hao Xie ◽  
Rongsheng Wang ◽  
...  

Abstract Stomach adenocarcinoma(STAD) is one of the deadliest cancers in the world. The expression levels of family members of mex-3 RNA that bound MEX3A (member A) and MEX3B (member B) were high expressions in different cancers and interconnected to deficient prognosis. The present research assessed the potential regarding the expression of MEX3A and MEX3B in STAD by analysing the facts of STAD (viz. The Cancer Genome Atlas). TCGA, MEX3A and MEX3B in the cancers were analyzed using TIMER2.0, Kaplan Meier Plotter, and cBioPortal. The data was visualized using version 4.0.3 of R. We found MEX3A and MEX3B had various expressions regarding major cancer and relevant common tissues. Especially, high expression of MEX3A and MEX3B had relationships with the OS (namely overall survival) with deficiency and RFS (viz. relapse-free survival) concerning STAD. The expressions of MEX3B had correlations to T stage with P being 0.012 and to the race with P being 0.049. MEX3B was highly expressed in T3 and T4 stages, and was highly expressed in the white race. MEX3A mutation had a better survival without diseases, with P being 0.0205. However, the situation was different with non-overall survival, with P being 0.194, in comparison with the patients who did not have MEX3A change. MEX3A and MEX3B on tumor pathogenesis might be related to "RNA splicing" and "spliceosomal complex" and "single-stranded RNA binding". We further investigated the association between MEX3A and MEX3B and immune cells. The mast cells of the most connections to MEX3A (R=-0.300, P<0.001) and the NK cells were positively correlation with MEX3B (R=0.590, P<0.001). It showed that they might be potential prognostic molecular biomarkers in patients with STAD.


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