Comprehensive Analysis of the Prognosis for Chemokine-Like Factor MARVEL Transmembrane Domain-Containing Family in Hepatocellular Carcinoma

Abstract Background and Purpose: Chemokine-like factor (CKLF) MARVEL transmembrane domain-containing family (CMTMs), including chemokine-like factor (CKLF) and CMTM1 to CMTM8. All of these genes participate in tumor development and metastasis of hepatocellular carcinoma (HCC). However, prognosis values and the distinct roles of different CMTMs in HCC are still un-clarified.Materials and Methods: To address this issue, the study explored the function of CMTM family members in the prognosis of HCC by TCGA dataset, UALCAN, Kaplan-Meier Plotter, MethSurv, TIMER2.0 databases.Results: The CKLF and CMTM1/3/4/7/8 mRNA expression was obviously elevated in HCC tissues, while CMTM2/5/6 was lowly expressed. Besides, the mRNA level of CMTMs was closely linked to cancer stage, node metastasis status and tumor grades in HCC patients. What’s more, the expression of CMTM2/5 was correlated with favorable overall survival (OS), while high expressions CKLF and CMTM1/7 were associated with poor OS. Simultaneously, low CKLF and CMTM1/4/7 expressions were significantly relevant to better progression-free survival (PFS), while low CMTM5 expression was apparently concerned with worse PFS. In DNA methylation level, 47 CpGs of CMTMs displayed markedly prognostic values. Multivariate cox analysis also revealed that affecting shorter OS outcomes prognostic factors of CKLF and CMTM7 were independent. GSEA results suggested that CKLF and CMTM7 participated in the development and progression of HCC accompanied with multiple biological processes. Furthermore, CMTMs were dramatically associated with tumor immune infiltrating cells (TIICs) (e.g., neutrophils cells), but CMTM8 expression level was no significant correlations with TIICs.Conclusion: This study renders new insight into the prognostic values of CMTM family members in HCC. Overall, our results indicated that CKLF and CMTM7 could be the prognostic biomarkers in HCC patients.

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Expression and prognostic roles of PRDXs gene family in hepatocellular carcinoma

Journal of Translational Medicine ◽

10.1186/s12967-021-02792-8 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Mingxing Xu ◽

Jianliang Xu ◽

Dun Zhu ◽

Rishun Su ◽

Baoding Zhuang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Acid Metabolism ◽

Family Members ◽

Interaction Network ◽

Genetic Alterations ◽

Database Analysis ◽

Kaplan Meier ◽

Canonical Pathways ◽

Human Protein Atlas ◽

Kaplan Meier Plotter

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.

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ASRGL1 Correlates With Immune Cell Infiltration in Hepatocellular Carcinoma and Can Serve as a Prognostic Biomarker

Frontiers in Oncology ◽

10.3389/fonc.2021.680070 ◽

2021 ◽

Vol 11 ◽

Author(s):

Cailin Xue ◽

Peng Gao ◽

Xiaohan Cui ◽

Xudong Zhang ◽

Jin Lei ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Mrna Expression ◽

Immune Cell ◽

Progression Free Survival ◽

Free Survival ◽

Kegg Pathways ◽

Interactive Analysis ◽

Kaplan Meier ◽

Hydrolysis Of ◽

Kaplan Meier Plotter

BackgroundThe enzyme L-asparaginase (ASRGL1) catalyzes the hydrolysis of L-asparagine (Asn) to L-aspartic acid (Asp) and ammonia. Numerous studies have shown a strong correlation between ASRGL1 expression and tumorigenesis. However, the expression and biological function of ASRGL1 in hepatocellular carcinoma (HCC) are still unclear.MethodsWe explored the mRNA expression of ASRGL1 in HCC using the HCCDB, Oncomine, and TIMER 2.0 databases. Western blotting and immunohistochemical analyses were also used to determine the mRNA expression of ASRGL1 in HCC. LinkedOmics was used to analyze the genes co-expressed with ASRGL1 and regulators including kinases, miRNAs, and transcription factors. The Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the co-expressed genes were also investigated using LinkedOmics. The correlation between ASRGL1 expression and immune infiltrates was analyzed using the TIMER 2.0 and Gene Expression Profiling Interactive Analysis (GEPIA) databases. The effects of ASRGL1 expression on patient outcome were investigated using the UALCAN and GEPIA databases, and the Kaplan–Meier plotter. c-Bioportal was used to explore the mutations of ASRGL1 in HCC.ResultsCompared with the adjacent tissues, ASRGL1 was upregulated in HCC. High ASRGL1 expression in HCC indicated poor relapse-free survival, progression-free survival, disease-specific survival, and overall survival. The expression of ASRGL1 was significantly correlated with infiltrating levels of B cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in HCC.ConclusionOur findings suggest that ASRGL1 is overexpressed in HCC and that ASRGL1 expression was significantly correlated with immune infiltration in HCC and prognosis. Therefore, ASRGL1 may serve as a biomarker for the early diagnosis and treatment of HCC.

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Mining prognostic markers of Asian hepatocellular carcinoma patients based on the apoptosis-related genes

BMC Cancer ◽

10.1186/s12885-021-07886-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Junbin Yan ◽

Jielu Cao ◽

Zhiyun Chen

Keyword(s):

Hepatocellular Carcinoma ◽

Regression Analysis ◽

Risk Score ◽

Roc Curve ◽

Prognostic Model ◽

Cox Regression ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Cox Analysis ◽

Kaplan Meier Plotter

Abstract Background Apoptosis-related genes(Args)play an essential role in the occurrence and progression of hepatocellular carcinoma(HCC). However, few studies have focused on the prognostic significance of Args in HCC. In the study, we aim to explore an efficient prognostic model of Asian HCC patients based on the Args. Methods We downloaded mRNA expression profiles and corresponding clinical data of Asian HCC patients from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The Args were collected from Deathbase, a database related to cell death, combined with the research results of GeneCards、National Center for Biotechnology Information (NCBI) databases and a lot of literature. We used Wilcoxon-test and univariate Cox analysis to screen the differential expressed genes (DEGs) and the prognostic related genes (PRGs) of HCC. The intersection genes of DEGs and PGGs were seen as crucial Args of HCC. The prognostic model of Asian HCC patients was constructed by least absolute shrinkage and selection operator (lasso)- proportional hazards model (Cox) regression analysis. Kaplan-Meier curve, Principal Component Analysis (PCA) analysis, t-distributed Stochastic Neighbor Embedding (t-SNE) analysis, risk score curve, receiver operating characteristic (ROC) curve, and the HCC data of ICGC database and the data of Asian HCC patients of Kaplan-Meier plotter database were used to verify the model. Results A total of 20 of 56 Args were differentially expressed between HCC and adjacent normal tissues (p < 0.05). Univariate Cox regression analysis showed that 10 of 56 Args were associated with survival time and survival status of HCC patients (p < 0.05). There are seven overlapping genes of these 20 and 10 genes, including BAK1, BAX, BNIP3, CRADD, CSE1L, FAS, and SH3GLB1. Through Lasso-Cox analysis, an HCC prognostic model composed of BAK1, BNIP3, CSE1L, and FAS was constructed. Kaplan-Meier curve, PCA, t-SNE analysis, risk score curve, ROC curve, and secondary verification of ICGC database and Kaplan-Meier plotter database all support the reliability of the model. Conclusions Lasso-Cox regression analysis identified a 4-gene prognostic model, which integrates clinical and gene expression and has a good effect. The expression of Args is related to the prognosis of HCC patients, but the specific mechanism remains to be further verified.

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Overexpressed pseudogene MT1L associated with tumor immune infiltrates and indicates a worse prognosis in BLCA

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02231-4 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Yanpeng Ding ◽

Nuomin Liu ◽

Mengge Chen ◽

Yulian Xu ◽

Sha Fang ◽

...

Keyword(s):

Immune Cells ◽

Biological Function ◽

Prognostic Biomarker ◽

Poor Survival ◽

Common Cancer ◽

Kaplan Meier ◽

Cox Analysis ◽

Kaplan Meier Plotter ◽

Worse Prognosis

Abstract Background BLCA is a common cancer worldwide, and it is both aggressive and fatal. Immunotherapy (ICT) has achieved an excellent curative effect in BLCA; however, only some BLCA patients can benefit from ICT. MT1L is a pseudogene, and a previous study suggested that MT1L can be used as an indicator of prognosis in colorectal cancer. However, the role of MT1L in BLCA has not yet been determined. Methods Data were collected from TCGA, and logistic regression, Kaplan-Meier plotter, and multivariate Cox analysis were performed to demonstrate the correlation between the pseudogene MT1L and the prognosis of BLCA. To identify the association of MT1L with tumor-infiltrating immune cells, TIMER and TISIDB were utilized. Additionally, GSEA was performed to elucidate the potential biological function. Results The expression of MT1L was decreased in BLCA. Additionally, MT1L was positively correlated with immune cells, such as Tregs (ρ = 0.708) and MDSCs (ρ = 0.664). We also confirmed that MT1L is related to typical markers of immune cells, such as PD-1 and CTLA-4. In addition, a high MT1L expression level was associated with the advanced T and N and high grade in BLCA. Increased expression of MT1L was significantly associated with shorter OS times of BLCA patients (p < 0.05). Multivariate Cox analysis revealed that MT1L expression could be an independent prognostic factor in BLCA. Conclusion Collectively, our findings demonstrated that the pseudogene MT1L regulates the immune microenvironment, correlates with poor survival, and is an independent prognostic biomarker in BLCA.

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Functional lncRNA-miRNA-mRNA Networks in Response to Baicalein Treatment in Hepatocellular Carcinoma

BioMed Research International ◽

10.1155/2021/8844261 ◽

2021 ◽

Vol 2021 ◽

pp. 1-18

Author(s):

Xin Zhao ◽

Dongyang Tang ◽

Xiaofei Chen ◽

Shaoqing Chen ◽

Cheng Wang

Keyword(s):

Hepatocellular Carcinoma ◽

Treatment Group ◽

Cancer Progression ◽

Messenger Rna ◽

Noncoding Rna ◽

Mirna Targets ◽

Kaplan Meier ◽

Dmso Treatment ◽

Human Protein Atlas ◽

Kaplan Meier Plotter

Introduction. Baicalein has been shown to have antitumor activities in several cancer types. However, its acting mechanisms remain to be further investigated. This work is aimed at exploring the functional long noncoding RNA (lncRNA)/microRNA (miRNA)/messenger RNA (mRNA) triplets in response to baicalein in hepatocellular carcinoma (HCC) cell to understand the mechanisms of baicalein in HCC. Methods. Differentially expressed lncRNAs (DELs) and miRNAs (DEMs) in HCC cell treated with baicalein were first screened using GSE95504 and GSE85511, respectively. miRNA targets for DELs were predicted and intersected with DEMs, after which the miRNA expression was validated using ENCORI and its prognostic value was assessed using Kaplan-Meier plotter. Potential miRNA targets were predicted by 3 prediction tools, after which expression level was validated at UALCAN and Human Protein Atlas. Kaplan-Meier plotter was used to evaluate the effects of these genes on overall survival and recurrence-free survival of HCC patients. Enrichment analyses for these genes were performed at DAVID. Results. Here, we identified 14 overlapping DELs and 26 overlapping DEMs in the baicalein treatment group than those in the DMSO treatment group. Subsequently, by analyzing expression and clinical significance of miRNAs, hsa-miR-4443 was found as a highly potential miRNA target. Then, targets of hsa-miR-4443 were predicted and analyzed, and we found AKT1 was the most potential target for hsa-miR-4443. Hence, the lncRNAs-hsa-miR-4443-AKT1 axis that can respond to baicalein was established. Conclusion. Collectively, we elucidated a role of lncRNAs-hsa-miR-4443-AKT1 pathway in response to baicalein treatment in HCC, which could help us understand the roles of baicalein in inhibiting cancer progression and may provide novel insights into the mechanisms behind HCC progression.

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Mining expression and prognosis of FOLR1 in ovarian cancer by using Oncomine and Kaplan-Meier plotter

Pteridines ◽

10.1515/pteridines-2019-0020 ◽

2019 ◽

Vol 30 (1) ◽

pp. 158-164

Author(s):

Qingyuan Su ◽

Qingyuan Lv ◽

Ruijin Wu

Keyword(s):

Ovarian Cancer ◽

Mrna Expression ◽

Ovarian Tumor ◽

Ovarian Tissue ◽

Progression Free Survival ◽

Free Survival ◽

Normal Ovarian Tissue ◽

Oncomine Database ◽

Kaplan Meier ◽

Kaplan Meier Plotter

Abstract Objective: To further explore folate receptor 1 (FOLR1) gene expression in ovarian cancer and its association with patients’ prognosis by deep mining the Oncomine and Kaplan-Meier plotter databases. Methods: FOLR1 mRNA expression data of ovarian cancer were retrieved from the Oncomine database and further analyzed by comparing tumor to healthy tissue. The prognostic value of FOLR1 in ovarian cancer was analyzed by Kaplan-Meier Plotter, an online survival analysis database. Results A total of 439 studies were included in the Oncomine database in multiple types of cancers. Of the 439 studies, there were 54 with statistical differences for the expression of FOLR1, 19 with increased expression of FOLR1 and 35 with decreased expression comparing ovarian cancer to normal ovary tissue. After searching the Oncomine database, six datasets were discovered comparing the mRNA expression in ovarian tumor to healthy tissue. FOLR1 mRNA expression in ovarian tumor was significantly higher than that of normal ovarian tissue (all p<0.05). The Kaplan-Meier Plotter database analyzed the correlation between FOLR1 expression and ovarian cancer patient’s prognosis. A significant difference of progression-free survival between FOLR1 high and low expressing groups was found in ovarian cancer patients (HR=1.14, 95%CI: 1.00-1.29, p=0.043). However, the overall survival was not statistically different between high and low FOLR1 expressing patients (HR=0.95, 95%CI: 0.84-1.09, p=0.48). Conclusion FOLR1 mRNA was found to be highly expressed in ovarian tumor compared to normal ovarian tissue. Elevated FOLR1 mRNA expression was associated with the poor progression-free survival.

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Repeated CyberKnife stereotactic body radiation therapy in hepatocellular carcinoma

Radiation Oncology ◽

10.1186/s13014-020-1457-z ◽

2020 ◽

Vol 15 (1) ◽

Cited By ~ 1

Author(s):

Jing Sun ◽

Can Ouyang ◽

Xiaoyun Chang ◽

Aimin Zhang ◽

Quan Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Radiation Therapy ◽

Stereotactic Body Radiation Therapy ◽

Medical Center ◽

Survival Rates ◽

Progression Free Survival ◽

Interval Time ◽

Stereotactic Body Radiation ◽

Kaplan Meier ◽

Radiation Induced

Abstract Background To explore the survival and side effects of repeated CyberKnife stereotactic body radiation therapy (CK-SBRT) on hepatocellular carcinoma patients. Methods 24 HCC patients were collected at The Fifth Medical Center of PLA General Hospital from November 2011 to July 2016. They received second-course CK-SBRT with a prescribed dose of 50(48–55) Gy/5-8fx, and a single dose of 10 (7–11) Gy/fx. Cumulative overall survival rates (OS), progression-free survival rates (PFS) and local control rates (LC) were calculated by Kaplan-Meier method. Results All patients finished their radiotherapy plans. The 1-,2- and 3-year cumulative OS rate were 95.8,81.1 and 60.8%. The 1-,2- and 3-year LC rate were 95.5,90.7 and 90.7%, respectively. The 1-, 2- and 3-year PFS were 74.8, 49.2 and 39.4%, respectively. 16 patients complained of fatigue during second-course therapy, 2 patients showed Grade 2 gastrointestinal reaction, 1 patient was diagnosed radiation-induced liver disease and none died. PFS was significantly higher in the interval time < 12 months group than in the interval time ≥ 12 months group (p = 0.030). Conclusions It is preliminarily believed that re-CK-SBRT is an effective and safe treatment for HCC patients, but the treatment criteria should be strictly controlled.

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Comprehensive analysis of key lncRNAs in HCV-positive hepatocellular carcinoma

Archives of Medical Science ◽

10.5114/aoms.2020.100675 ◽

2021 ◽

Vol 17 (1) ◽

pp. 142-151

Author(s):

Jingqi Liu ◽

Ligang Chen ◽

Jinshui Pan ◽

Meiya Chen ◽

Jingping Zhou ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Normal Liver ◽

Comprehensive Analysis ◽

Differentially Expressed ◽

Expression Levels ◽

Go Analysis ◽

The Public ◽

Kaplan Meier ◽

Tcga Dataset ◽

Underlying Mechanisms

IntroductionHepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Despite the therapeutic advances in HCC in the past few decades, the mortality rate of HCC is still high. Hepatitis C (HCV) infection is one of the major etiological risk factors of HCCs. However, the underlying mechanisms of HCV-induced hepatocarcinogenesis remain largely unclear.Material and methodsOur study represented the comprehensive analysis of differentially expressed lncRNAs in HCV-positive HCC for the first time by analyzing the public dataset GSE17856. Co-expression network and gene ontology (GO) analysis revealed the functions of those differentially expressed lncRNAs.ResultsWe identified 256 upregulated lncRNAs and 198 downregulated lncRNAs in HCV- positive HCC compared to the normal liver tissues. Co-expression network and GO analysis showed that these lncRNAs were involved in regulating metabolism, energy pathways, proliferation and the immune response. Seven lncRNAs (LOC341056, CCT6P1, PTTG3P, LOC643387, LOC100133920, C3P1 and C22orf45) were identified as key lncRNAs and co-expressed with more than 100 differentially expressed genes (DEGs) in HCV-related HCC. Kaplan-Meier analysis showed that higher expression levels of LOC643387, PTTG3P, LOC341056, CCT6P1 and lower expression levels of C3P1 and C22orf45 were associated with shorter survival time in the TCGA dataset.ConclusionsWe believe that this study can provide novel potential therapeutic and prognostic biomarkers for HCV-positive HCC.

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Identification of Prognostic Biomarkers Among DAAM1, FHOD1,FMN2 and INF2 in Breast Cancer Patients

10.21203/rs.3.rs-742870/v1 ◽

2021 ◽

Author(s):

Yin-Hai Dai ◽

Fuping Li ◽

Wei-Jie Kong ◽

Xue-Qin Zhang ◽

Mao Wang ◽

...

Keyword(s):

Breast Cancer ◽

T Cells ◽

Immune Cells ◽

Survival Data ◽

Mrna Level ◽

Mrna Levels ◽

Breast Cancer Patients ◽

Kaplan Meier ◽

Migration Of Cells ◽

Kaplan Meier Plotter

Abstract Background:The formin family proteins are main regulators of actin filaments, which play a crucial role in the migration of cells and carcinogenesis.The specific functions of the formin family proteins in breast cancer still remain unknown.To dissolve this problem,we selected four formin proteins including DAAM1,FHOD1, FMN2 and INF2 and investigated their mRNA expression and survival data in BC(breast carcinoma) patients using diverse databases.Methods:we used these databases including Oncomine, Ualcan, GEPIA 2,HumanProtein Atlas,Metascape,Kaplan-Meier plotter,cBioPortal and TIMER and the software of Cytoscape in our study.Results:DAAM1 and FMN2 were lowly expressed in BC tissues,while FHOD1 and INF2 were highly expressed in BC tissues.The expression levels of DAAM1, FMN2 and FHOD1 were relevant to major subclasses,and the mRNA level of FHOD1 was related to cancer staging.Moreover,High mRNA levels of FHOD1 and INF2 were relevant to poorer prognosis of BC patients,while low mRNA level of DAAM1 was correlated with better prognosis.we also found that there were significant associations between the expressions of DAAM1,FHOD1,FMN2 and INF2 and six types of infiltrated immune cells(B Cells,CD4+T cells,CD8+T cells, neutrophil,macrophage,and dendritic cell).Conclusions:our study indicated that FHOD1 and INF2 were potential biomarkers to identify short survival of BC patients,FMN2 was potential prognostic marker to suggest favorable survival of BC patients.

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Bioinformatics Analysis and Insights for The Role of COMMD7 in Hepatocellular Carcinoma

10.21203/rs.3.rs-79438/v1 ◽

2020 ◽

Author(s):

Xuehui Peng ◽

Yonggang He ◽

Xiaobing Huang ◽

Nan You ◽

Huiying Gu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Bioinformatics Analysis ◽

Tissue Expression ◽

The Cancer Genome Atlas ◽

Research Progress ◽

Kaplan Meier ◽

Tumor Tissues ◽

Cancer Genome Atlas ◽

Kaplan Meier Plotter

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.

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