scholarly journals SULF2 Is a Prognostic Biomarker and Correlated with Tumor Associated Macrophages in Gastric Cancer

2021 ◽  
Author(s):  
Tong-Bo Wang ◽  
Ze-Feng Li ◽  
Xiao-Jie Zhang ◽  
Chong-Yuan Sun ◽  
He Fei ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Immunity ◽  
Cancer Progression ◽  
Immune Cell ◽  
Underlying Mechanism ◽  
Key Factors ◽  
Tumor Associated Macrophages ◽  
Programmed Cell Death 1 ◽  
Tumor Immune Microenvironment ◽  
Pathway Analyses

Abstract Background: Recently, the mutual effects of tumor cells and the tumor immune microenvironment have been identified as key factors in promoting cancer progression. Sulfatase 2 (SULF2) encodes an extracellular endoglucosamine‑6-sulfatase, which could remodel the highly sulfated domains of heparan sulfate. The abnormal expression of SULF2 is reported to play an important role in the carcinogenesis of many kinds of cancer. However, the prognostic value of SULF2 and its correlation with immune cell infiltration in gastric cancer (GC) remain unclear. Results: SULF2 expression was significantly increased in GC compared with gastric normal tissue, especially in the advanced stage GC. In addition, high SULF2 expression significantly predicted an unfavorable prognosis in GC patients (overall survival P=0.0074), particularly who had metastatic lymph nodes. Besides, pathway analyses of SULF2 in GC revealed SULF2 may take part in extracellular structure organization, cell-cell adhesion and proteoglycans in cancer, etc. Importantly, the expression level of SULF2 was found to be positively correlated with the infiltration levels of tumor associated macrophages (TAMs). Moreover, SULF2 expression in GC positively correlated with expression of several immune cell markers, including monocyte markers, TAMs markers and programmed cell death 1 ligand 1 (PD-L1), suggesting its role in regulating tumor immunity.Conclusion: This study identified distinct expression and prognostic values of SULF2 in GC using public databases. Significantly, our findings shed light on the role of SULF2 in GC progression and provided an underlying mechanism that SULF2 expression might modulate tumor immunity by regulating the infiltration of TAMs in GC.

EDD1 predicts prognosis and regulates gastric cancer growth in vitro and in vivo via miR-22

2016 ◽  
Vol 0 (0) ◽  
Author(s):  
Min Yang ◽  
Nan Jiang ◽  
Qi-wei Cao ◽  
Qing Sun
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Patient Survival ◽  
Underlying Mechanism ◽  
Gastric Cancer Cells ◽  
Cancer Tissues

Abstract Gastric cancer is the most common digestive malignant tumor worldwild. EDD1 was reported to be frequently amplified in several tumors and played an important role in the tumorigenesis process. However, the biological role and potential mechanism of EDD1 in gastric cancer remains poorly understood. In this study, we are aim to investigate the effect of EDD1 on gastric cancer progression and to explore the underlying mechanism. The results showed the significant up-regulation of EDD1 in -gastric cancer cell tissues and lines. The expression level of EDD1 was also positively associated with advanced clinical stages and predicted poor overall patient survival and poor disease-free patient survival. Besides, EDD1 knockdown markedly inhibited cell viability, colony formation, and suppressed tumor growth. Opposite results were obtained in gastric cancer cells with EDD1 overexpression. EDD1 knockdown was also found to induce gastric cancer cells apoptosis. Further investigation indicated that the oncogenic role of EDD1 in regulating gastric cancer cells growth and apoptosis was related to its PABC domain and directly through targeting miR-22, which was significantly down-regulated in gastric cancer tissues. Totally, our study suggests that EDD1 plays an oncogenic role in gastric cancer and may be a potential therapeutic target for gastric cancer.

scholarly journals LncRNA FEZF1-AS1 Promotes Multi-Drug Resistance of Gastric Cancer Cells via Upregulating ATG5

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhifu Gui ◽  
Zhenguo Zhao ◽  
Qi Sun ◽  
Guoyi Shao ◽  
Jianming Huang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Underlying Mechanism ◽  
Multi Drug Resistance ◽  
Gastric Cancer Cells ◽  
Poor Overall Survival

Long non-coding RNAs (lncRNAs) play important roles in human cancers including gastric cancer (GC). Dysregulation of lncRNAs is involved in a variety of pathological activities associated with gastric cancer progression and chemo-resistance. However, the role and molecular mechanisms of FEZF1-AS1 in chemoresistance of GC remain unknown. In this study, we aimed to determine the role of FEZF1-AS1 in chemoresistance of GC. The level of FEZF1-AS1 in GC tissues and GC cell lines was assessed by qRT-PCR. Our results showed that the expression of FEZF1-AS1 was higher in gastric cancer tissues than in adjacent normal tissues. Multivariate analysis identified that high level of FEZF1-AS1 is an independent predictor for poor overall survival. Increased FEZF1-AS1 expression promoted gastric cancer cell proliferation in vitro. Additionally, FEZF1-AS1 was upregulated in chemo-resistant GC tissues. The regulatory effect of FEZF1-AS1 on multi-drug resistance (MDR) in GC cells and the underlying mechanism was investigated. It was found that increased FEZF1-AS1 expression promoted chemo-resistance of GC cells. Molecular interactions were determined by RNA immunoprecipitation (RIP) and the results showed that FEZF1-AS1 regulated chemo-resistance of GC cells through modulating autophagy by directly targeting ATG5. The proliferation and autophagy of GC cells promoted by overexpression of LncFEZF1-AS1 was suppressed when ATG5 was knocked down. Moreover, knockdown of FEZF1-AS1 inhibited tumor growth and increased 5-FU sensitivity in GC cells in vivo. Taken together, this study revealed that the FEZF1-AS1/ATG5 axis regulates MDR of GC cells via modulating autophagy.

scholarly journals Follistatin-like 1 (FSTL1) is a Prognostic Biomarker and Correlated with Immune Cell Infiltration in Gastric Cancer

2020 ◽  
Author(s):  
Li Li ◽  
Shanshan Huang ◽  
Yangyang Yao ◽  
Jun Chen ◽  
Junhe Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Immunity ◽  
Survival Data ◽  
Immune Cell ◽  
Bioinformatic Analysis ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Western Blot Assay ◽  
Immune Infiltration ◽  
Normal Tissues

Abstract Background: Follistatin-like 1 (FSTL1) plays a central role in the progression of tumor and tumor immunity. However, the effect of FSTL1 on the prognosis and immune infiltration of gastric cancer (GC) remains to be elucidated.Method: The expression of FSTL1 data was analyzed in Oncomine and TIMER databases. Analyses of clinical parameters and survival data were conducted by Kaplan-Meier plotter and immunohistochemistry. Western blot assay and real‐time quantitative PCR (RT-qPCR) was using to analyzed protein and mRNA expression, respectively. The correlations between FSTL1 and cancer immune infiltrates was analyzed by Tumor Immune Estimation Resource (TIME), Gene Expression Profiling Interactive Analysis (GEPIA) and LinkedOmics database.Results: The expression of FSTL1 was significantly higher in GC tissues than in normal tissues, and bioinformatic analysis and Immunohistochemistry (IHC) indicated that high FSTL1 expression significantly correlated with poor prognosis in GC. Moreover, FSTL1 was predicted as an independent prognostic factor in GC patients. Bioinformatics analysis results suggested that FSTL1 mainly involved in tumor progression and tumor immunity. And significant correlations were found between FSTL1 expression and immune cell infiltration in GC.Conclusion: The study effectively revealed useful information about FSTL1 expression, prognostic values, potential functional networks and impact of tumor immune infiltration in GC. In summary, FSTL1 can be used as a biomarker for prognosis and evaluating immune cell infiltration in GC.

scholarly journals The significance of the co-existence of osteopontin and tumor-associated macrophages in gastric cancer progression

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Chang-Ni Lin ◽  
Chih-Jung Wang ◽  
Ying-Jui Chao ◽  
Ming-Derg Lai ◽  
Yan-Shen Shan
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Tumor Associated Macrophages ◽  
Gastric Cancer Progression

scholarly journals A Pan-Cancer Study: The Immunological and Prognostic Significance of Aberrant SPP1 Expression on Tumors

2021 ◽  
Author(s):  
Tian peng Huang ◽  
Wei Ye ◽  
Xue jiao Lin
Keyword(s):  
Tumor Immunity ◽  
Cancer Progression ◽  
Immune Cell ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Multiple Cancer ◽  
Multiple Tumor ◽  
Cancer Types

Abstract Background Secretory phosphoprotein 1 (SPP1) is a glyco-phosphoprotein that is widely expressed in a variety of cancer cells. Current studies have identified that SPP1 is differentially expressed in a variety of cancer cell species. However, there are few studies on the level of SPP1 expression in different types of cancer and its clinical significance. Methods In this study, we analyzed SPP1 levels and its significance in 33 different cancer types by using The Cancer Genome Atlas (TCGA) database. The study analyzed the correlation between SPP1 expression and tumor immunity. Results The results showed that SPP1 transcript levels were aberrantly expressed in most tumors. Univariate Cox analysis showed that SPP1 was strongly associated with Overall survival in multiple tumor types. We also found that SPP1 was significantly correlated with tumor immune microenvironment, tumor immune cells, and tumor infiltrating lymphocyte markers. The correlation of SPP1 with Tumor mutational load (TMB) and Microsatellite instability (MSI) also predicts its role in assessing the efficacy of immunotherapy. Gene set enrichment analysis of 33 cancer types provided further evidence for the relationship between SPP1 levels and cancer progression and immune cell infiltration. Conclusion our study concludes that SPP1 plays an important role in tumorigenesis and tumor immunity and can be used as a marker for the assessment of clinical indicators in multiple cancer types.

scholarly journals Identification of INHBA as a Potential Biomarker for Gastric Cancer by Comprehensive Analysis

2021 ◽  
Author(s):  
Guangjie Liu ◽  
Xiao-jie Hu ◽  
Yuxuan Jia ◽  
Bing-jie Huo ◽  
Cheng Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Immune Cell ◽  
Underlying Mechanism ◽  
Bioinformatic Analysis ◽  
Tgf Beta ◽  
Normal Tissues ◽  
Potential Biomarker

Abstract Inhibin subunit beta A (INHBA) is a member of the TGF-beta (transforming growth factor-beta) superfamily proteins, which plays a fundamental role in various cancers. However, little is known about the exact role of INHBA in patients with gastric cancer (GC). The present study aims to explore the relationship between INHBA and GC and detect the underlying mechanisms. Multiple bioinformatic approaches were first preformed basing on TIMER, GEPIA2, GEO, Oncomine and UALCAN databases, which revealed that INHBA was highly elevated in GC. This result was proved by Immunohistochemistry (IHC) and real time polymerase chain reaction (RT-PCR) in 65 cases of GC tissues in our study. The bioinformatic analysis also revealed that high expression of INHBA was significantly related to unfavorable prognosis of GC. To detect the underlying mechanism, further analysis was performed basing on Kaplan Meier plotter database and found that poor prognosis of GC was related to infiltration of different enriched immune-cell subgroups. That was INHBA being negatively correlated with B cell while positively correlated with CD8 + T cells, macrophage, neutrophil and dendritic cell infiltration. However, there was week significant methylation level change between tumor and normal tissues. Moreover, INHBA mainly enriched on cancer-related signaling pathways, including TGF-beta signaling pathway, ECM-receptor signaling pathway, PID ALK1/2 pathway, and AGE-RAGE signaling pathway, which provide a new insight for future in-depth study.

scholarly journals The proteasome regulator PSME4 drives immune evasion and abrogates anti-tumor immunity in NSCLC

2021 ◽  
Author(s):  
Aaron Javitt ◽  
Merav D. Shmueli ◽  
Matthias P. Kramer ◽  
Aleksandra A. Kolodziejczyk ◽  
Ivan J. Cohen ◽  
...  
Keyword(s):  
Protein Degradation ◽  
Tumor Immunity ◽  
Cancer Progression ◽  
Immune Evasion ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Cell Lung Carcinoma ◽  
Tumor Inflammation

Protein degradation by proteasomes is important for the immune response against tumors. Antigens generated by the proteasome promote immune cell infiltration into tumors and improve tumor response to immunotherapy. For example, immunoproteasomes – a subset of proteasomes induced by inflammatory signals – may improve the response of melanomas to immune checkpoint inhibitors (ICI) by eliciting tumor inflammation. Yet, it is unclear whether and how protein degradation by proteasomes impacts cancer progression and contributes to immune evasion and resistance. Here, we profile the proteasome-cleaved peptides in lung cancers and find that PSME4 serves as a novel inhibitory regulator of the immunoproteasome, playing an anti-inflammatory role in cancer. Biochemical assays combined with scRNA-seq, immunopeptidomics and in vivo analyses demonstrate that PSME4 promotes an immunosuppressive environment around the tumor and abrogates anti-tumor immunity by inhibiting antigen presentation and attenuating tumor inflammation. Furthermore, we find that PSME4 expression is correlated with responsiveness to ICI across several cancer types. Our findings suggest that PSME4-mediated regulation of proteasome activity is a novel mechanism of immune evasion in non-small-cell lung carcinoma and may be targeted therapeutically for restoring anti-tumor immunity.

scholarly journals Follistatin-like 1 (FSTL1) is a prognostic biomarker and correlated with immune cell infiltration in gastric cancer

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Li Li ◽  
Shanshan Huang ◽  
Yangyang Yao ◽  
Jun Chen ◽  
Junhe Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Immunity ◽  
Survival Data ◽  
Immune Cell ◽  
Bioinformatic Analysis ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Western Blot Assay ◽  
Immune Infiltration ◽  
Normal Tissues

Abstract Background Follistatin-like 1 (FSTL1) plays a central role in the progression of tumor and tumor immunity. However, the effect of FSTL1 on the prognosis and immune infiltration of gastric cancer (GC) remains to be elucidated. Methods The expression of FSTL1 data was analyzed in Oncomine and TIMER databases. Analyses of clinical parameters and survival data were conducted by Kaplan-Meier plotter and immunohistochemistry. Western blot assay and real-time quantitative PCR (RT-qPCR) were used to analyze protein and mRNA expression, respectively. The correlations between FSTL1 and cancer immune infiltrates were analyzed by Tumor Immune Estimation Resource (TIME), Gene Expression Profiling Interactive Analysis (GEPIA), and LinkedOmics database. Results The expression of FSTL1 was significantly higher in GC tissues than in normal tissues, and bioinformatic analysis and immunohistochemistry (IHC) indicated that high FSTL1 expression significantly correlated with poor prognosis in GC. Moreover, FSTL1 was predicted as an independent prognostic factor in GC patients. Bioinformatics analysis results suggested that FSTL1 mainly involved in tumor progression and tumor immunity. And significant correlations were found between FSTL1 expression and immune cell infiltration in GC. Conclusions The study effectively revealed useful information about FSTL1 expression, prognostic values, potential functional networks, and impact of tumor immune infiltration in GC. In summary, FSTL1 can be used as a biomarker for prognosis and evaluating immune cell infiltration in GC.

scholarly journals The Human Cytomegalovirus US31 Gene Predicts Favorable Survival and Regulates the Tumor Microenvironment in Gastric Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Sisi Ye ◽  
Yuanbo Hu ◽  
Chenbin Chen ◽  
Sian Chen ◽  
Xinya Tong ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Human Cytomegalovirus ◽  
Immune Cell ◽  
Migration And Invasion ◽  
Tumor Immune Microenvironment ◽  
Potential Prognostic Factor ◽  
Polymerase Chain ◽  
Cancer Tissues

Human cytomegalovirus (HCMV) is an oncogenic virus associated with tumorigenesis. Our previous study revealed that the HCMV US31 gene interacted with NF-κB2 and mediated inflammation through macrophages. However, there are few reports on the role of US31 in gastric cancer (GC). The aim of this study was to investigate the expression of the US31 gene in GC tissue and assess its role in the occurrence and development of GC. US31 expression in 573 cancer tissues was analyzed using immunohistochemistry. Results showed that US31 was significantly associated with tumor size (P = 0.005) and distant metastasis (P < 0.001). Higher US31 expression indicated better overall survival in GC patients. Overexpression of US31 significantly inhibited the proliferation, migration, and invasion of GC cells in vitro (P < 0.05). Furthermore, expression levels of CD4, CD66b, and CD166 were positively correlated with US31, suggesting that it was involved in regulating the tumor immune microenvironment of GC. RNA sequencing, along with quantitative real-time polymerase chain reaction, confirmed that the expression of US31 promoted immune activation and secretion of inflammatory cytokines. Overall, US31 inhibited the malignant phenotype and regulated tumor immune cell infiltration in GC; these results suggest that US31 could be a potential prognostic factor for GC and may open the door for a new immunotherapy strategy.

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