CYSTM1: A Novel Biomarker for Hepatocellular Carcinoma Prognosis

Poor Prognosis ◽

Early Stage ◽

Human Tumor ◽

The Cancer Genome Atlas ◽

Data Set ◽

Kaplan Meier ◽

Cancer Genome Atlas ◽

Cox Proportional Hazard Regression ◽

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.

CPXM1: a novel biomarker for gastric cancer prognosis

10.21203/rs.3.rs-337128/v1 ◽

2021 ◽

Author(s):

Jun Du ◽

Mengxiang Zhu ◽

Wenwu Yan ◽

Changsheng Yao ◽

Qingyi Li ◽

...

Keyword(s):

Gastric Cancer ◽

Poor Prognosis ◽

The Cancer Genome Atlas ◽

Cancer Prognosis ◽

Signal Pathways ◽

Data Set ◽

Kaplan Meier ◽

Cancer Genome Atlas ◽

Cox Proportional Hazard Regression ◽

Abstract Background The molecular role of carboxypeptidase X, M14 family member (CPXM1) in oncogenesis or tumor progression remains unclear. The aim of this study was to determine whether CPXM1 can be used as a potential prognostic biomarker for gastric cancer (GC). Methods We first demonstrated the relationship between CPXM1 expression and GC in various public databases. Secondly, the expression of CPXM1 in GC tissues was further verified by immunohistochemical staining using tissue microarray containing 96 cases of GC patients. Kaplan–Meier analysis and a Cox proportional hazard regression model were performed to evaluate the relationship between the expression of CPXM1 and the survival of GC patients. Finally, we used the expression data of CPXM1 in The Cancer Genome Atlas database to predict CPXM1-related signaling pathways through bioinformatics analysis. Results The expression level of CPXM1 in GC tissues was significantly correlated with tumor size (p = 0.041) and lymph node metastasis (p = 0.014). In addition, Kaplan–Meier analysis showed that the expression of CPXM1 in GC tissues was significantly associated with poor prognosis (p = 0.011). Multivariate analysis indicated that CPXM1 is a potential predictor of poor prognosis in GC patients (p = 0.026). The results of biosynthesis analysis demonstrated that the data set of CPXM1 high expression was mainly enriched in cancer-related signal pathways. Conclusion CPXM1 is an effective biomarker for the prognosis of GC patients and may play a key role in the occurrence and progression of GC.

High expression of PARD3 predicts poor prognosis in hepatocellular carcinoma

Scientific Reports ◽

10.1038/s41598-021-90507-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Songwei Li ◽

Jian Huang ◽

Fan Yang ◽

Haiping Zeng ◽

Yuyun Tong ◽

...

Keyword(s):

Dendritic Cells ◽

Poor Prognosis ◽

The Cancer Genome Atlas ◽

Functional Enrichment ◽

Predictive Capacity ◽

Immune Infiltration ◽

Cancer Genome Atlas ◽

Liver Hepatocellular Carcinoma ◽

AbstractHepatocellular carcinoma (HCC) is one of the most commonly cancers with poor prognosis and drug response. Identifying accurate therapeutic targets would facilitate precision treatment and prolong survival for HCC. In this study, we analyzed liver hepatocellular carcinoma (LIHC) RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA), and identified PARD3 as one of the most significantly differentially expressed genes (DEGs). Then, we investigated the relationship between PARD3 and outcomes of HCC, and assessed predictive capacity. Moreover, we performed functional enrichment and immune infiltration analysis to evaluate functional networks related to PARD3 in HCC and explore its role in tumor immunity. PARD3 expression levels in 371 HCC tissues were dramatically higher than those in 50 paired adjacent liver tissues (p < 0.001). High PARD3 expression was associated with poor clinicopathologic feathers, such as advanced pathologic stage (p = 0.002), vascular invasion (p = 0.012) and TP53 mutation (p = 0.009). Elevated PARD3 expression also correlated with lower overall survival (OS, HR = 2.08, 95% CI = 1.45–2.98, p < 0.001) and disease-specific survival (DSS, HR = 2.00, 95% CI = 1.27–3.16, p = 0.003). 242 up-regulated and 71 down-regulated genes showed significant association with PARD3 expression, which were involved in genomic instability, response to metal ions, and metabolisms. PARD3 is involved in diverse immune infiltration levels in HCC, especially negatively related to dendritic cells (DCs), cytotoxic cells, and plasmacytoid dendritic cells (pDCs). Altogether, PARD3 could be a potential prognostic biomarker and therapeutic target of HCC.

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

Biochemical Genetics ◽

10.1007/s10528-021-10178-0 ◽

2021 ◽

Author(s):

Senbang Yao ◽

Wenjun Chen ◽

He Zuo ◽

Ziran Bi ◽

Xiuqing Zhang ◽

...

Keyword(s):

Liver Cancer ◽

Oxidative Dna Damage ◽

Tumor Grade ◽

The Cancer Genome Atlas ◽

Kaplan Meier ◽

Human Protein Atlas ◽

Cancer Genome Atlas ◽

The Relationship ◽

Kaplan Meier Plotter

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.

Prognostic Significance of NBEAL2 in Liver hepatocellular carcinoma

10.21203/rs.3.rs-471663/v1 ◽

2021 ◽

Author(s):

Yanghui Wen ◽

Hui Su ◽

Wuke Wang ◽

Feng Ren ◽

Haitao Jiang ◽

...

Keyword(s):

Expression Profiles ◽

Prognostic Significance ◽

The Cancer Genome Atlas ◽

Clinicopathological Parameters ◽

Chi Square ◽

Kaplan Meier ◽

Chi Square Test ◽

Liver Hepatocellular Carcinoma ◽

Abstract Background: NBEAL2 is a member of the BEACH domain–containing protein (BDCP) family and little is known about the relationship between NBEAL2 and malignancy.Methods: We downloaded the Gene expression profiles and clinical data of Liver hepatocellular carcinoma(LIHC) form the Cancer Genome Atlas (TCGA) dataset. The expression difference of NBEAL2 in LIHC tissues and adjacent nontumor tissues was analyzed by R software. The relationship between NBEAL2 expression and clinicopathological parameters was evaluate by Chi-square test. The effect of NBEAL2 expression on survival were assessed by Kaplan–Meier survival analysis and Cox proportional hazards regression model. GSEA was used to explore the potential molecular mechanism of NBEAL2 in LIHC.Results: Up-regulation of NBEAL2 expression was detected in the LIHC tissue compared with adjacent nontumor tissues(P < 0.001). The chi-square test showed that no significant correlation between the expression level of NBEAL2 and various clinicopathological parameters (including T, N and M classifications) were detected. The Kaplan–Meier curves suggested that lower NBEAL2 expression was related with poor prognosis. The results of Multivariate analysis revealed that a lower expression of NBEAL2 in LIHC was an independent risk of poor overall survival (HR, 8.873; 95% CI, 1.159-67.936; P = 0.035). GSEA suggested that multiple tumor-related metabolic pathways were evidently enriched in samples with the low-NBEAL2 expression phenotype. Conlusion: NBEAL2 might act as an tumor suppressor gene in the progression of LIHC but the precise role of NBELA2 in LIHC needs further vertification.

The Prediction and Prognostic Significance of INPP5K Expression in Patients with Liver Cancer

BioMed Research International ◽

10.1155/2020/9519235 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Ruobing Wang ◽

Yan Jiao ◽

Yanqing Li ◽

Siyang Ye ◽

Guoqiang Pan ◽

...

Keyword(s):

Liver Cancer ◽

Mrna Expression ◽

Poor Prognosis ◽

Prognostic Significance ◽

The Cancer Genome Atlas ◽

Inositol Polyphosphate ◽

Chi Square ◽

Cancer Genome Atlas ◽

Poor Outcomes ◽

Liver cancer is a devastating disease for humans with poor prognosis. Although the survival rate of patients with liver cancer has improved in the past decades, the recurrence and metastasis of liver cancer are still obstacles for us. Inositol polyphosphate-5-phosphatase K (INPP5K) belongs to the family of phosphoinositide 5-phosphatases (PI 5-phosphatases), which have been reported to be associated with cell migration, polarity, adhesion, and cell invasion, especially in cancers. However, there have been few studies on the correlation of INPP5K and liver cancer. In this study, we explored the prognostic significance of INPP5K in liver cancer through bioinformatics analysis of data collected from The Cancer Genome Atlas (TCGA) database. Chi-square and Fisher exact tests were used to evaluate the relationship between INPP5K expression and clinical characteristics. Our results showed that low INPP5K expression was correlated with poor outcomes in liver cancer patients. Univariate and multivariate Cox analyses demonstrated that low INPP5K mRNA expression played a significant role in shortening overall survival (OS) and relapse-free survival (RFS), which might serve as the useful biomarker and prognostic factor for liver cancer. In conclusion, low INPP5K mRNA expression is an independent risk factor for poor prognosis in liver cancer.

Identification of RASSF1A Promoter Hypermethylation as a Biomarker for Hepatocellular Carcinoma

10.21203/rs.3.rs-54668/v2 ◽

2020 ◽

Author(s):

Gang Xu ◽

Xiaoxiang Zhou ◽

Jiali Xing ◽

Yao Xiao ◽

Bao Jin ◽

...

Keyword(s):

Promoter Methylation ◽

Meta Analysis ◽

Promoter Hypermethylation ◽

Analysis Data ◽

Clinicopathological Characteristics ◽

The Cancer Genome Atlas ◽

Large Tumor ◽

Kaplan Meier ◽

Cancer Genome Atlas

Abstract Background: RAS association domain family protein 1A (RASSF1A) promoter hypermethylation is suggested to be linked to hepatocellular carcinoma (HCC), but the results remained controversial.Methods: We evaluated how RASSF1A promoter hypermethylation affects HCC risk and its clinicopathological characteristics through meta-analysis. Data on DNA methylation in HCC and relevant clinical data were also collected based on The Cancer Genome Atlas (TCGA) database to investigate the prognostic role of RASSF1A promoter hypermethylation in HCC.Results: Forty-four articles involving 4,777 individuals were enrolled in the pooled analyses. The RASSF1A promoter methylation rate was notably higher in the HCC cases than the non-tumor cases and healthy individuals, and was significantly related to hepatitis B virus (HBV) infection-positivity and large tumor size. Kaplan–Meier survival analysis revealed that HCC cases with RASSF1A promoter hypermethylation had worse outcomes. Receiver operating characteristic curves confirmed that RASSF1A promoter methylation may be a marker of HCC-related prognoses.Conclusions: RASSF1A promoter hypermethylation is a promising biomarker for the diagnosis of HCC from tissue and peripheral blood, and is an emerging therapeutic target against HCC.

ATG101 as a Novel Prognostic Biomarker Related to Immunotherapy in Pan-cancer

10.21203/rs.3.rs-430028/v1 ◽

2021 ◽

Author(s):

Zijian Zhang ◽

Jinggang Mo ◽

Chong Jin ◽

Hao Jiang ◽

Zhongtao Liu ◽

...

Keyword(s):

Critical Role ◽

Tissue Expression ◽

The Cancer Genome Atlas ◽

Immune Checkpoints ◽

Integrated Analysis ◽

Tumour Immunity ◽

Kaplan Meier ◽

Cancer Genome Atlas ◽

The Relationship ◽

Pan Cancer

Abstract Background: ATG101 plays a significant role in the occurrence and development of tumours by regulating autophagy. Our study aimed to research the correlation between the expression of ATG101 and tumour prognosis and its role in tumour immunity. Methods: First, integrated analysis of The Cancer Genome Atlas and Genotype-Tissue Expression portals were used to analyse the expression of ATG101. Then, we used Kaplan–Meier curves for survival analysis. Next, we analysed the relationship between ATG101 expression and six immune cells, the immune microenvironment and immune checkpoints. Besides, we analysed the relationship between the expression of ATG101 and methyltransferase. Finally, we used GSEA to study the function of ATG101 in COAD and LIHC. Results: Integrated analysis showed that ATG101 was overexpressed in different tumours. Kaplan–Meier curves found that ATG101 was associated with poor prognosis in most tumours. We found that that ATG101 can be used as a target and prognostic marker of tumour immunotherapy for different tumours. We also found that ATG101 regulates DNA methylation. GSEA analysis showed that ATG101 may play a critical role in COAD and LIHC.Conclusions: Our study highlights the significance of ATG101 in the study of tumour immunity from a pan-cancer perspective.

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):

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.

Characterization of the prognostic values of the NDRG family in gastric cancer

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284819858507 ◽

2019 ◽

Vol 12 ◽

pp. 175628481985850 ◽

Cited By ~ 4

Author(s):

Chaoran Yu ◽

Xiaohui Hao ◽

Sen Zhang ◽

Wenjun Hu ◽

Jianwen Li ◽

...

Keyword(s):

Gastric Cancer ◽

T Cells ◽

Poor Prognosis ◽

Wide Spectrum ◽

Mitotic Cell ◽

High Risk Group ◽

The Cancer Genome Atlas ◽

Follicular Helper ◽

Kaplan Meier ◽

Cancer Genome Atlas

Background: The N-myc downstream-regulated gene ( NDRG) family, NDRG1-4, has been involved in a wide spectrum of biological functions in multiple cancers. However, their prognostic values remain sparse in gastric cancer (GC). Therefore, it is crucial to systematically investigate the prognostic values of the NDRG family in GC. Methods: The prognostic values of the NDRG family were evaluated by Kaplan–Meier Plotter and SurvExpress. The mRNA of the NDRG family was investigated in The Cancer Genome Atlas (TCGA). Transcription factors (TFs) and miRNAs associated with the NDRG family were predicted by NetworkAnalysis. The prognostic values of DNA methylation levels were analyzed by MethSurv. The correlation between immune cells and the NDRG family was evaluated by the Tumor Immune Estimation Resource (TIMER) database. Results: High levels of mRNA expression of NDRG2 and NDRG3 were associated with a favorable prognosis in all GCs. In HER2− GC, NDRG1 was significantly associated with a poor prognosis of GC [hazard ratio (HR) = 1.65, 95% confidence interval (CI) = 1.16–2.33, p = 0.0046]. In HER2+ GC, NDRG4 showed a poor prognosis (HR = 1.4, 95% CI: 1.06–1.85, p = 0.017). NDRG4 was an independent prognostic factor in recurrence-free survival by TCGA cohort. The low-risk NDRG-signature group displayed a significantly favorable survival outcome than the high-risk group (HR = 1.76, 95% CI: 1.2–2.59, p = 0.00385). The phosphorylated protein NDRG1 (NDRG1_pT346) displayed a favorable overall survival and was significantly associated with HER2 and phosphorylated HER2. Epidermis development was the top biological process (BP) for coexpressed genes associated with NDRG1 and NDRG4, while mitotic nuclear division and mitotic cell processes were the top BPs for NDRG2 and NDRG3, respectively. Overall, 6 CpGs of NDRG1, 4 CpGs of NDRG2, 3 CpGs of NDRG3 and 24 CpGs of NDRG4 were associated with significant prognosis. CD4+ T-cells showed the highest correlation with NDRG4 (correlation = 0.341, p = 2.14e−11). Furthermore, BCL6 in follicular helper T-cells (Tfh) cells showed the highest association with NDRG4 (correlation = 0.438, p = 00e+00). Conclusions: This study analyzed the multilevel prognostic values and biological roles of the NDRG family in GC.

The m6A Methylation Gene SNRPC can be used as a Biomarker for the Prognosis and Immunotherapy of Hepatocellular Carcinoma

10.21203/rs.3.rs-320369/v1 ◽

2021 ◽

Author(s):

Jihao Cai ◽

Minglei Zhou ◽

Jianxin Xu

Keyword(s):

Cancer Genome ◽

The Cancer Genome Atlas ◽

Rna Methylation ◽

Kaplan Meier ◽

Pathogenic Factors ◽

Therapeutic Value ◽

Cancer Genome Atlas ◽

Checkpoint Inhibitor Therapy ◽

Genome Consortium

Abstract Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. Due to its complex pathogenic factors, the prognosis of HCC is poor. Therefore, a credible prognostic biomarker is urgently needed for this disease. N6-methyladenosine (m6A) RNA methylation plays an important role in the tumorigenesis, progression and prognosis of many tumors. However, studies on the prognostic and therapeutic value of this modification in HCC are lacking.Case Presentation: The HCC RNA-seq profiles in The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, including 421 LIHC and 440 LIRI samples respectively, were used in this study. The expressive distinction of 21 RNA methylation regulators between HCC and normal tissue were firstly assessed and SNRPC was obtained. Then the expression of SNRPC was validated as a risk factor for prognosis by Kaplan-Meier analysis and employed to establish a nomogram with T pathologic stage. By GSVA and GSEA analyses, we found SNRPC was mainly related to protein metabolism and immune process. Further, ESTIMATE, MCP-counter and single sample GSEA (ssGSEA) algorithm showed high-SNRPC expression group had lower stromal scores, a lower abundance of endothelial cells, fibroblasts and immune infiltration. Ultimately, Tumor Immune Dysfunction and Exclusion (TIDE) analysis exhibited high-SNRPC expression group showed non-response to immune checkpoint inhibitor therapy, especially to a PD-1 inhibitor.Conclusion: SNRPC could serve as valuable prognostic and immunotherapeutic marker in HCC. We provide here an accurate nomogram for clinical diagnosis using SNRPC as a biomarker.