scholarly journals Dynamin 3 Gene as a Tumor Suppressor and an Independent Predictive Factor of Poor Prognosis in Patients with Gastric Cancer

2021 ◽  
Author(s):  
Ru-Hong Tu ◽  
Jian-Xian Lin ◽  
Jian-Wei Xie ◽  
Jia-Bin Wang ◽  
Jun Lu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Tumor Suppressor ◽  
Predictive Factor ◽  
Poor Prognosis ◽  
Immune Cell ◽  
The Cancer Genome Atlas ◽  
Independent Predictive Factor ◽  
Stomach Adenocarcinoma ◽  
Low Expression

Abstract Gastric cancer is a leading cause of death from malignant tumors worldwide. With the development of genome sequencing technology, an increasing number of key driver genes and tumor suppressors have been discovered. Some studies have suggested that Dynamin 3 (DNM3) is a novel tumor suppressor; however, the role of DNM3 in malignancy remains unclear. We performed a systematic analysis using The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) cohorts, and 160 patients with stomach adenocarcinoma at Fujian Medical University Union Hospital (FJMUUH) (48 quantitative PCR [qPCR] and 112 immunohistochemistry). DNM3 expression was found to be downregulated in gastric cancer compared to that in paraneoplastic tissue. Low expression of DNM3 was mainly associated with DNM3 promoter hypermethylation status. Low expression of DNM3 can upregulate the tumor cell cycle and oxidative phosphorylation process and downregulate immune regulation, and Th17 and Th2 immune cell infiltration was increased in patients with lower expression of DNM3. Patients with a lower DNM3 expression had a higher rate of lymph node metastasis and poor prognosis. In summary, DNM3 is a tumor suppressor and an independent predictive factor of poor prognosis that regulates the cell cycle and immunosuppression in the tumor microenvironment in gastric cancer via methylation.

scholarly journals Characteristics of the Immune Cell Infiltration Landscape in Gastric Cancer to Assistant Immunotherapy

2022 ◽  
Vol 12 ◽  
Author(s):  
Chenlu Li ◽  
Jingjing Pan ◽  
Yinyan Jiang ◽  
Yan Yu ◽  
Zhenlin Jin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Signaling Pathways ◽  
Poor Prognosis ◽  
Immune Cell ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Therapeutic Responses

Background: Gastric cancer (GC) was usually associated with poor prognosis and invalid therapeutical response to immunotherapy due to biological heterogeneity. It is urgent to screen reliable indices especially immunotherapy-associated parameters that can predict the therapeutic responses to immunotherapy of GC patients.Methods: Gene expression profile of 854 GC patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets (GSE84433) with their corresponding clinical and somatic mutation data. Based on immune cell infiltration (ICI) levels, molecular clustering classification was performed to identify subtypes and ICI scores in GC patients. After functional enrichment analysis of subtypes, we further explored the correlation between ICI scores and Tumor Mutation Burden (TMB) and the significance in clinical immunotherapy response.Results: Three subtypes were identified based on ICI scores with distinct immunological and prognostic characteristics. The ICI-cluster C, associated with better outcomes, was characterized by significantly higher stromal and immune scores, T lymphocytes infiltration and up-regulation of PD-L1. ICI scores were identified through using principal component analysis (PCA) and the low ICI scores were consistent with the increased TMB and the immune-activating signaling pathways. Contrarily, the high-ICI score cluster was involved in the immunosuppressive pathways, such as TGF-beta, MAPK and WNT signaling pathways, which might be responsible for poor prognosis of GC. External immunotherapy and chemotherapy cohorts validated the patients with lower ICI scores exhibited significant therapeutic responses and clinical benefits.Conclusion: This study elucidated that ICI score could sever as an effective prognostic and predictive indicator for immunotherapy in GC. These findings indicated that the systematic assessment of tumor ICI landscapes and identification of ICI scores have crucial clinical implications and facilitate tailoring optimal immunotherapeutic strategies.

scholarly journals ADAMTS12 acts as a tumor microenvironment related cancer promoter in gastric cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yangming Hou ◽  
Yingjuan Xu ◽  
Dequan Wu
Keyword(s):  
Gastric Cancer ◽  
Tumor Microenvironment ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Tumor Promoter ◽  
Protein Protein Interaction ◽  
Oxidative Phosphorylation Pathway ◽  
Cox Proportional Hazard Regression

AbstractThe infiltration degree of immune and stromal cells has been shown clinically significant in tumor microenvironment (TME). However, the utility of stromal and immune components in Gastric cancer (GC) has not been investigated in detail. In the present study, ESTIMATE and CIBERSORT algorithms were applied to calculate the immune/stromal scores and the proportion of tumor-infiltrating immune cell (TIC) in GC cohort, including 415 cases from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were screened by Cox proportional hazard regression analysis and protein–protein interaction (PPI) network construction. Then ADAMTS12 was regarded as one of the most predictive factors. Further analysis showed that ADAMTS12 expression was significantly higher in tumor samples and correlated with poor prognosis. Gene Set Enrichment Analysis (GSEA) indicated that in high ADAMTS12 expression group gene sets were mainly enriched in cancer and immune-related activities. In the low ADAMTS12 expression group, the genes were enriched in the oxidative phosphorylation pathway. CIBERSORT analysis for the proportion of TICs revealed that ADAMTS12 expression was positively correlated with Macrophages M0/M1/M2 and negatively correlated with T cells follicular helper. Therefore, ADAMTS12 might be a tumor promoter and responsible for TME status and tumor energy metabolic conversion.

scholarly journals Comprehensive Analysis of the Immune Infiltrates of Pyroptosis in Kidney Renal Clear Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhuolun Sun ◽  
Changying Jing ◽  
Xudong Guo ◽  
Mingxiao Zhang ◽  
Feng Kong ◽  
...  
Keyword(s):  
High Risk ◽  
Cell Carcinoma ◽  
Poor Prognosis ◽  
Immune Cell ◽  
Risk Model ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Risk Scores

Kidney renal clear cell carcinoma (KIRC) has long been identified as a highly immune-infiltrated tumor. However, the underlying role of pyroptosis in the tumor microenvironment (TME) of KIRC remains poorly described. Herein, we systematically analyzed the prognostic value, role in the TME, response to ICIs, and drug sensitivity of pyroptosis-related genes (PRGs) in KIRC patients based on The Cancer Genome Atlas (TCGA) database. Cluster 2, by consensus clustering for 24 PRGs, presented a poor prognosis, likely because malignancy-related hallmarks were remarkably enriched. Additionally, we constructed a prognostic prediction model that discriminated well between high- and low-risk patients and was further confirmed in external E-MTAB-1980 cohort and HSP cohort. By further analyzing the TME based on the risk model, higher immune cell infiltration and lower tumor purity were found in the high-risk group, which presented a poor prognosis. Patients with high risk scores also exhibited higher ICI expression, indicating that these patients may be more prone to profit from ICIs. The sensitivity to anticancer drugs that correlated with model-related genes was also identified. Collectively, the pyroptosis-related prognosis risk model may improve prognostic information and provide directions for current research investigations on immunotherapeutic strategies for KIRC patients.

Low expression of MAP1LC3B, associated with low Beclin-1, predicts lymph node metastasis and poor prognosis of gastric cancer

Tumor Biology ◽  
2016 ◽  
Vol 37 (11) ◽  
pp. 15007-15017 ◽  
Author(s):  
Shuangjin Yu ◽  
Guanghua Li ◽  
Zhao Wang ◽  
Zhixiong Wang ◽  
Chuangqi Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Poor Prognosis ◽  
Beclin 1 ◽  
Node Metastasis ◽  
Low Expression

scholarly journals Preoperative prealbumin levels on admission as an independent predictive factor in patients with gastric cancer

Medicine ◽  
2020 ◽  
Vol 99 (11) ◽  
pp. e19196 ◽  
Author(s):  
Hongliang Zu ◽  
Huiling Wang ◽  
Chunfeng Li ◽  
Yingwei Xue
Keyword(s):  
Gastric Cancer ◽  
Predictive Factor ◽  
Independent Predictive Factor

scholarly journals CPXM1: a novel biomarker for gastric cancer prognosis

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.

scholarly journals NAP1L1 Functions as a Tumor Promoter via Recruiting Hepatoma-Derived Growth Factor/c-Jun Signal in Hepatocellular Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Ye-wei Zhang ◽  
Qian Chen ◽  
Bo Li ◽  
Hai-Yang Li ◽  
Xue-Ke Zhao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Growth Factor ◽  
Poor Prognosis ◽  
Quantitative Polymerase Chain Reaction ◽  
The Cancer Genome Atlas ◽  
Tumor Promoter ◽  
Mechanism Analysis ◽  
Factor C

NAP1L1 has been reported to be significantly involved in the carcinogenesis of hepatocellular carcinoma (HCC). Yet, its detailed molecular basis is still to be determined. Based on the analysis of The Cancer Genome Atlas (TCGA) database, NAP1L1 mRNA was found to be upregulated and predicted the poor prognosis initially. Subsequently, consistent with the prediction, the upregulated expression of NAP1L1 mRNA and protein levels was confirmed by quantitative polymerase chain reaction (qPCR), Western blot, and immunohistochemistry assays. Upregulated NAP1L1 protein positively promoted the disease progression and poor prognosis of HCC. In addition, NAP1L1 protein expression was considered as an independent prognostic factor in HCC. Inhibition of NAP1L1 expression by siRNA or shRNA pathway significantly reduced the cell proliferation and cell cycle transformation in vitro and in vivo. Mechanism analysis first showed that the function of NAP1L1 was to recruit hepatoma-derived growth factor (HDGF), an oncogene candidate widely documented in tumors. Furthermore, the latter interacted with c-Jun, a key oncogenic transcription factor that can induce the expression of cell cycle factors and thus stimulate the cell growth in HCC. Finally, transfecting HDGF or c-Jun could reverse the suppressive effects on HCC growth in NAP1L1-suppressed HCC cells. Our data indicate that NAP1L1 is a potential oncogene and acts via recruiting HDGF/c-Jun in HCC.

scholarly journals Low expression of RecQ‑like helicase 5 is associated with poor prognosis in patients with gastric cancer

2019 ◽  
Author(s):  
Yijia Lin ◽  
Huashe Wang ◽  
Xinyou Wang ◽  
Miao Li ◽  
Honglei Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Poor Prognosis ◽  
Low Expression

scholarly journals Low Expression of FBXO45 Is Associated with Gastric Cancer Progression and Poor Prognosis

2017 ◽  
Vol 37 (1) ◽  
pp. 191-196 ◽  
Author(s):  
NORIMICHI KOGURE ◽  
TAKEHIKO YOKOBORI ◽  
KYOICHI OGATA ◽  
BOLAG ALTAN ◽  
ERITO MOCHIKI ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Gastric Cancer Progression ◽  
Low Expression

scholarly journals Increased IGFBP7 Expression Correlates with Poor Prognosis and Immune Infiltration in Gastric Cancer: An Integrated Bioinformatics Analysis

2020 ◽  
Author(s):  
Qiaoyun Zhao ◽  
Rulin Zhao ◽  
Conghua Song ◽  
Huan Wang ◽  
Jianfang Rong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Poor Prognosis ◽  
Bioinformatics Analysis ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Biological Processes ◽  
Coexpressed Genes

Abstract Background Insulin-like growth factor binding protein-7 (IGFBP7) contributes to multiple biological processes in various tumors. However, the role of IGFBP7 in gastric cancer (GC) is still undetermined. The study aims to explore the role of IGFBP7 in GC via an integrated bioinformatics analysis.Methods IGFBP7 expression levels in GC and its normal gastric tissues were analyzed using multiple databases, including the Tumor Immune Estimation Resource (TIMER), Oncomine, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The methylation analysis was conducted with MEXPRESS, UALCAN and Xena online tools. The survival analysis was conducted using the Kaplan-Meier Plotter and Gene Expression Profiling Interactive Analysis (GEPIA) databases. Coexpressed genes of IGFBP7 were selected with the cBioPortal tool and enrichment analysis was conducted with the clusterProfiler package in R software. Gene set enrichment analysis (GSEA) was performed to explore the IGFBP7-related biological processes involved in GC. Correlations between IGFBP7 and immune cell infiltrates were analyzed using the TIMER database.Results IGFBP7 expression was significantly upregulated in GC and correlated with stage, grade, tumor status and Helicobacter pylori infection. High IGFBP7 expression and low IGFBP7 methylation levels were significantly associated with short survival of patients with GC. Univariate and multivariate analyses revealed that IGFBP7 was an independent risk factor for GC. The coexpressed genes LHFPL6, SEPTIN4, HSPB2, LAYN and GGT5 predicted unfavorable outcomes of GC. Enrichment analysis showed that the coexpressed genes were involved in extracellular matrix (ECM)-related processes. GSEA indicated that IGFBP7 was positively related to ECM and inflammation-related pathways. TIMER analysis indicated that the IGFBP7 expression level was strongly correlated with genes related to various infiltrating immune cells in GC, especially with gene markers of tumor associated macrophages (TAMs).Conclusions We demonstrate that increased IGFBP7 expression correlates with poor prognosis and immune cell infiltration in GC. IGFBP7 might be a potential biomarker for the diagnosis and targeted therapy for GC.

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