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

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.

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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 ◽

The Relationship

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.

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Identification of novel autophagy-related lncRNAs associated with a poor prognosis of colon adenocarcinoma through bioinformatics analysis

Scientific Reports ◽

10.1038/s41598-021-87540-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Dejun Wu ◽

Zhenhua Yin ◽

Yisheng Ji ◽

Lin Li ◽

Yunxin Li ◽

...

Keyword(s):

High Risk ◽

Poor Prognosis ◽

Notch Pathway ◽

Colon Adenocarcinoma ◽

High Risk Group ◽

The Cancer Genome Atlas ◽

Future Research ◽

Risk Patients ◽

Cancer Genome Atlas ◽

Immune Score

AbstractLncRNAs play a pivotal role in tumorigenesis and development. However, the potential involvement of lncRNAs in colon adenocarcinoma (COAD) needs to be further explored. All the data used in this study were obtained from The Cancer Genome Atlas database, and all analyses were conducted using R software. Basing on the seven prognosis-related lncRNAs finally selected, we developed a prognosis-predicting model with powerful effectiveness (training cohort, 1 year: AUC = 0.70, 95% Cl = 0.57–0.78; 3 years: AUC = 0.71, 95% Cl = 0.6–0.8; 5 years: AUC = 0.76, 95% Cl = 0.66–0.87; validation cohort, 1 year: AUC = 0.70, 95% Cl = 0.58–0.8; 3 years: AUC = 0.73, 95% Cl = 0.63–0.82; 5 years: AUC = 0.68, 95% Cl = 0.5–0.85). The VEGF and Notch pathway were analyzed through GSEA analysis, and low immune and stromal scores were found in high-risk patients (immune score, cor = − 0.15, P < 0.001; stromal score, cor = − 0.18, P < 0.001) , which may partially explain the poor prognosis of patients in the high-risk group. We screened lncRNAs that are significantly associated with the survival of patients with COAD and possibly participate in autophagy regulation. This study may provide direction for future research.

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CYSTM1: A Novel Biomarker for Hepatocellular Carcinoma Prognosis

10.21203/rs.3.rs-150866/v1 ◽

2021 ◽

Author(s):

Jun Du ◽

Jinguo Wang

Keyword(s):

Hepatocellular Carcinoma ◽

Poor Prognosis ◽

Early Stage ◽

Human Tumor ◽

The Cancer Genome Atlas ◽

Data Set ◽

Kaplan Meier ◽

Cancer Genome Atlas ◽

Cox Proportional Hazard Regression ◽

The Relationship

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.

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TMIC-03. UPREGULATION OF THE NLRC4 INFLAMMASOME CONTRIBUTES TO POOR PROGNOSIS IN GLIOMA PATIENTS

Neuro-Oncology ◽

10.1093/neuonc/noz175.1037 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi247-vi247

Author(s):

Jaejoon Lim ◽

Youngjoon Park ◽

Minjun Kim ◽

Juwon Ahn ◽

KyuBum Kwack ◽

...

Keyword(s):

Poor Prognosis ◽

Tumor Development ◽

The Cancer Genome Atlas ◽

Immune Functions ◽

Potential Therapeutic Target ◽

Clinical Prognosis ◽

Tumor Microenvironments ◽

Kaplan Meier ◽

Cancer Genome Atlas

Abstract Inflammation in tumor microenvironments is implicated in the pathogenesis of tumor development. In particular, inflammasomes, which modulate innate immune functions, are linked to tumor growth and anticancer responses. However, the role of the NLRC4 inflammasome in gliomas remains unclear. Here, we investigated whether the upregulation of the NLRC4 inflammasome is associated with the clinical prognosis of gliomas. We analyzed the protein expression and localization of NLRC4 in glioma tissues from 11 patients by immunohistochemistry. We examined the interaction between the expression of NLRC4 and clinical prognosis via a Kaplan-Meier survival analysis. The level of NLRC4 protein was increased in brain tissues, specifically, in astrocytes, from glioma patients. NLRC4 expression was associated with a poor prognosis in glioma patients, and the upregulation of NLRC4 in astrocytomas was associated with poor survival. Furthermore, hierarchical clustering of data from the Cancer Genome Atlas dataset showed that NLRC4 was highly expressed in gliomas relative to that in a normal healthy group. Our results suggest that the upregulation of the NLRC4 inflammasome contributes to a poor prognosis for gliomas and presents a potential therapeutic target and diagnostic marker.

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A novel assessing system for predicting the prognosis of gastric cancer

Epigenomics ◽

10.2217/epi-2019-0151 ◽

2019 ◽

Vol 11 (11) ◽

pp. 1251-1266

Author(s):

Siheng Lin ◽

Rui Zhou ◽

Dongqiang Zeng ◽

Jiani Wu ◽

Jianhua Wu ◽

...

Keyword(s):

Gastric Cancer ◽

Tumor Microenvironment ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Diagnostic Tools ◽

Expression Data ◽

Protein Coding ◽

Kaplan Meier ◽

Cancer Genome Atlas ◽

Gastric Cancer Patients

Aim: To develop novel diagnostic tools that can predict the prognosis of gastric cancer. Material & methods: Using RNA expression data from The Cancer Genome Atlas and Gene Expression Omnibus, we established protein-coding RNAs-noncoding RNAs-tumor microenvironment type (PNM) scores, which contain signatures of tumor protein coding genes (P), tumor noncoding genes (N) and immune/stroma cells in tumor microenvironment (M) to predict the prognosis of gastric cancer. Results & conclusion: Based on PNM scores, gastric cancer patients were divided into three subgroups and Kaplan–Meier survival curves revealed significant differences among the subgroups (p < 0.001). Our study showed that the PNM scores could be used as a robust predicting tool for the prognosis of gastric cancer.

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Construct ion of co - expression modules related to survival by WGCNA and identif ication of potential prognostic biomarkers in glioblastoma

10.21203/rs.3.rs-27332/v1 ◽

2020 ◽

Author(s):

Jing Zhou ◽

Hao Guo ◽

Likun Liu ◽

Shulan Hao ◽

Zhi Guo ◽

...

Keyword(s):

T Cells ◽

Poor Prognosis ◽

Single Gene ◽

Intervention Strategy ◽

Clinical Information ◽

The Cancer Genome Atlas ◽

Hub Genes ◽

P53 Signaling ◽

Significant Difference ◽

Cancer Genome Atlas

Abstract Background: Glioblastoma (GBM) is a malignant brain tumor with poor prognosis. However, the potential pathogenesis and therapeutic target s still needs to be explored.Methods: Herein, The Cancer Genome Atlas (TCGA) expression profile data and clinical information were downloaded, and the Weighted Gene Co-expression Network Analysis (WGCNA) was conducted. Subsequently, hub genes which closely related to the poor prognosis of GBM were obtained. Further, the relationship between the genes of interest and prognosis of GBM patients, and immune microenvironment were analysed. Patients from TCGA were divided into high- and low-risk groups.Results: Top 10 hub genes (CDC20, NCAPH, CDCA5, BUB1, CDCA8, PBK, KIF2C, TPX2, TTK and TOP2A) were obtained. Then, we performed single-gene analysis on CDCA5 and CDCA8 as genes of interest. We found that their expression levels were closely related to overall survival (OS). They had good correlations with the genes that regulate cell cycle in p53 signaling pathway. Moreover, it revealed that high amplication of CDCA5 was correlated with CD8 + T cells while CDCA8 with CD4 + T cells, and the expression of these two genes showed a significant difference in OS.Conclusions: These results might provide new molecular targets and intervention strategy for GBM.

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Bioinformatics Analysis Identifies CPZ as a Tumor Immunology Biomarker For Gastric Cancer

Current Bioinformatics ◽

10.2174/1574893615999200707145643 ◽

2020 ◽

Vol 15 ◽

Author(s):

Yuan Gu ◽

Ying Gao ◽

Xiaodan Tang ◽

Huizhong Xia ◽

Kunhe Shi

Keyword(s):

Gastric Cancer ◽

T Cells ◽

Signaling Pathway ◽

Tumor Immunology ◽

Bioinformatics Analysis ◽

Human Cancer ◽

Disease Free Survival ◽

Kaplan Meier ◽

Potential Biomarker ◽

Pathway Regulation

Background: Gastric cancer (GC) is one of the most common malignancies worldwide. However, the biomarkers for the prognosis and diagnosis of Gastric cancer were still need. Objective: The present study aimed to evaluate whether CPZ could be a potential biomarker for GC. Method: Kaplan-Meier plotter (http://kmplot.com/analysis/) was used to determine the correlation between CPZ expression and overall survival (OS) and disease-free survival (DFS) time in GC [9]. We analyzed CPZ expression in different types of cancer and the correlation of CPZ expression with the abundance of immune infiltrates, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells, via gene modules using TIMER Database. Results: The present study identified that CPZ was overexpressed in multiple types of human cancer, including Gastric cancer. We found that overexpression of CPZ correlates to the poor prognosis of patients with STAD. Furthermore, our analyses show that immune infiltration levels and diverse immune marker sets are correlated with levels of CPZ expression in STAD. Bioinformatics analysis revealed that CPZ was involved in regulating multiple pathways, including PI3K-Akt signaling pathway, cGMP-PKG signaling pathway, Rap1 signaling pathway, TGF-beta signaling pathway, regulation of cell adhesion, extracellular matrix organization, collagen fibril organization, collagen catabolic process. Conclusion: This study for the first time provides useful information to understand the potential roles of CPZ in tumor immunology and validate it to be a potential biomarker for GC.

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TRIM27 interacts with Iκbα to promote the growth of human renal cancer cells through regulating the NF-κB pathway

BMC Cancer ◽

10.1186/s12885-021-08562-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chengwu Xiao ◽

Wei Zhang ◽

Meimian Hua ◽

Huan Chen ◽

Bin Yang ◽

...

Keyword(s):

Cell Lines ◽

Prognostic Indicator ◽

The Cancer Genome Atlas ◽

Mrna Levels ◽

Loss Of Function ◽

Protein Levels ◽

Kaplan Meier ◽

Cancer Genome Atlas

Abstract Background The tripartite motif (TRIM) family proteins exhibit oncogenic roles in various cancers. The roles of TRIM27, a member of the TRIM super family, in renal cell carcinoma (RCC) remained unexplored. In the current study, we aimed to investigate the clinical impact and roles of TRIM27 in the development of RCC. Methods The mRNA levels of TRIM27 and Kaplan–Meier survival of RCC were analyzed from The Cancer Genome Atlas database. Real-time PCR and Western blotting were used to measure the mRNA and protein levels of TRIM27 both in vivo and in vitro. siRNA and TRIM27 were exogenously overexpressed in RCC cell lines to manipulate TRIM27 expression. Results We discovered that TRIM27 was elevated in RCC patients, and the expression of TRIM27 was closely correlated with poor prognosis. The loss of function and gain of function results illustrated that TRIM27 promotes cell proliferation and inhibits apoptosis in RCC cell lines. Furthermore, TRIM27 expression was positively associated with NF-κB expression in patients with RCC. Blocking the activity of NF-κB attenuated the TRIM27-mediated enhancement of proliferation and inhibition of apoptosis. TRIM27 directly interacted with Iκbα, an inhibitor of NF-κB, to promote its ubiquitination, and the inhibitory effects of TRIM27 on Iκbα led to NF-κB activation. Conclusions Our results suggest that TRIM27 exhibits an oncogenic role in RCC by regulating NF-κB signaling. TRIM27 serves as a specific prognostic indicator for RCC, and strategies targeting the suppression of TRIM27 function may shed light on future therapeutic approaches.

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LAMB1 Is Related to the T Stage and Indicates Poor Prognosis in Gastric Cancer

Technology in Cancer Research & Treatment ◽

10.1177/15330338211004944 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110049

Author(s):

Tao Ran ◽

ZhiJi Chen ◽

LiWen Zhao ◽

Wei Ran ◽

JinYu Fan ◽

...

Keyword(s):

Gastric Cancer ◽

Poor Prognosis ◽

Hazard Models ◽

Proportional Hazard ◽

Kegg Analysis ◽

Proportional Hazard Models ◽

Cox Proportional Hazard ◽

Kaplan Meier ◽

Cox Proportional Hazard Models ◽

Gastric Cancer Patients

Background and Objective: Gastric cancer (GC) is a common tumor malignancy with high incidence and poor prognosis. Laminin is an indispensable component of basement membrane and extracellular matrix, which is responsible for bridging the internal and external environment of cells and transmitting signals. This study mainly explored the association of the LAMB1 expression with clinicopathological characteristics and prognosis in gastric cancer. Methods: The expression data and clinical information of gastric cancer patients were downloaded from The Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG). And we analyzed the relationship between LAMB1 expression and clinical characteristics through R. CIBERSORTx was used to calculate the absolute score of immune cells in gastric tumor tissues. Then COX proportional hazard models and Kaplan-Meier curves were performed to evaluate the role of LAMB1 and its influence on prognosis in gastric cancer patients. Finally, GO and KEGG analysis were applied for LAMB1-related genes in gastric cancer, and PPI network was constructed in Cytoscape software. Results: In the TCGA cohort, patients with gastric cancer frequently generated LAMB1 gene copy number variation, but had little effect on mRNA expression. Both in the TCGA and ACRG cohorts, the mRNA expression of LAMB1 in gastric cancer tissues was higher than it in normal tissues. All patients were divided into high expression group and low expression group according to the median expression level of LAMB1. The elevated expression group obviously had more advanced cases and higher infiltration levels of M2 macrophages. COX proportional hazard models and Kaplan-Meier curves revealed that patients with enhanced expression of LAMB1 have a worse prognosis. GO/KEGG analysis showed that LAMB1-related genes were enriched in PI3K-Akt signaling pathway, focal adhesion, ECM-receptor interaction, etc. Conclusions: The high expression of LAMB1 in gastric cancer is related to the poor prognosis of patients, and it may be related to microenvironmental changes in tumors.

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Transcriptome of Tumor-Infiltrating T Cells in Colorectal Cancer Patients Uncovered a Unique Gene Signature in CD4+ T Cells Associated with Poor Disease-Specific Survival

Vaccines ◽

10.3390/vaccines9040334 ◽

2021 ◽

Vol 9 (4) ◽

pp. 334

Author(s):

Salman M. Toor ◽

Varun Sasidharan Nair ◽

Reem Saleh ◽

Rowaida Z. Taha ◽

Khaled Murshed ◽

...

Keyword(s):

Colorectal Cancer ◽

T Cells ◽

T Cell Activation ◽

Cd4 T Cells ◽

Poor Prognosis ◽

Gene Signature ◽

The Cancer Genome Atlas ◽

Disease Specific Survival ◽

Unique Gene ◽

Disease Specific

Colorectal cancer (CRC) is influenced by infiltration of immune cell populations in the tumor microenvironment. While elevated levels of cytotoxic T cells are associated with improved prognosis, limited studies have reported associations between CD4+ T cells and disease outcomes. We recently performed transcriptomic profiling and comparative analyses of sorted CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) from bulk tumors of CRC patients with varying disease stages. In this study, we compared the transcriptomes of CD4+ with CD8+ TILs. Functional annotation pathway analyses revealed the downregulation of inflammatory response-related genes, while T cell activation and angiogenesis-related genes were upregulated in CD4+ TILs. The top 200 deregulated genes in CD4+ TILs were aligned with the cancer genome atlas (TCGA) CRC dataset to identify a unique gene signature associated with poor prognosis. Moreover, 69 upregulated and 20 downregulated genes showed similar trends of up/downregulation in the TCGA dataset and were used to calculate “poor prognosis score” (ppScore), which was significantly associated with disease-specific survival. High ppScore patients showed lower expression of Treg-, Th1-, and Th17-related genes, and higher expression of Th2-related genes. Our data highlight the significance of T cells within the TME and identify a unique candidate prognostic gene signature for CD4+ TILs in CRC patients.

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