scholarly journals Human Gastric Cancer Stem Cell (GCSC) Markers Are Prognostic Factors Correlated With Immune Infiltration of Gastric Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Tong Lin ◽  
Wenya Peng ◽  
Peipei Mai ◽  
E. Zhang ◽  
Lisheng Peng
Keyword(s):  
Gastric Cancer ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
Clinicopathological Parameters ◽  
Human Gastric Cancer ◽  
Nf Kappa B ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
Cancer Aggressiveness ◽  
Human Protein Atlas

The prognosis of patients with gastric cancer (GC) is still unsatisfying. Numerous markers of gastric cancer stem cells (GCSCs) have been identified and were thought to be related to cancer aggressiveness. However, the roles of GCSC markers in GC patients’ prognosis and immune infiltration remain unknown. Expression of GCSC markers was analyzed using Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA). Their associations with clinicopathological parameters were analyzed using UALCAN and LinkedOmics. Alternations and protein expression of GCSC markers were analyzed by cBioPortal and the Human Protein Atlas databases, respectively. The prognostic significance of GCSC markers was evaluated using Kaplan-Meier plotter. Correlations between the expression of GCSC markers and immune infiltration along with biomarkers of tumor-infiltrating immune cells (TIICs) were assessed combined Tumor Immune Estimation Resource and GEPIA. GeneMANIA was used to discover the interactive genes of GCSC markers, and enrichment analysis was performed using Database for Annotation, Visualization, and Integrated Discovery server. We identified six GCSC markers significantly up-expressed in GC, compared with normal stomach tissues. Among them, the overexpression of ICAM1, THY1, and CXCR4 significantly indicated adverse, while EPCAM indicated beneficial clinicopathological features of GC patients. The up-regulation of CXCR4 showed unfavorable prognostic significance, whereas EPCAM and TFRC showed the opposite. The six GCSC markers were all correlated with the infiltration and activation of distinct TIICs. Especially, ICAM1, THY1, and CXCR4 showed strongly positive correlations with tumor-associated macrophages. Besides, chemokine, Toll-like receptor, NF-kappa B, and HIF-1 signaling pathways might be involved in the regulation of GCSC markers on cancer development. This study proposed that GCSC markers might be promising targets of GC treatment to weaken cancer stem-like properties and strengthen anticancer immunity.

scholarly journals Prognostic values of E2F mRNA expression in human gastric cancer

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Theasha Manicum ◽  
Fubiao Ni ◽  
Yiming Ye ◽  
Xuhui Fan ◽  
Bi-Cheng Chen
Keyword(s):  
Gastric Cancer ◽  
Transcription Factors ◽  
Mrna Expression ◽  
Prognostic Significance ◽  
Family Members ◽  
Incidence Rates ◽  
Human Gastric Cancer ◽  
Kaplan Meier ◽  
E2f Transcription Factors ◽  
Transcription Activators

Gastric cancer (GC) is the second most frequent cause of cancer-related mortality in the world, with Eastern Asia having the highest incidence rates. E2F is a family of transcription factor proteins that has a variety of functions, which include control of cell cycle, cell differentiation, DNA damage response and cell death. E2F transcription factors are divided into two subfamilies: transcription activators (E2F transcription factors 1 (E2F1), 2 (E2F2) and 3a (E2F3a)) and repressors (E2F3b, E2F transcription factors 4 (E2F4), 5 (E2F5), 6 (E2F6), 7 (E2F7) and 8 (E2F8)). Studies have demonstrated that E2F had prognostic significance in a number of cancers. However, the entirety of the prognostic roles of E2F mRNA expression in GC has not yet been apparently determined. In the present study, the prognostic value of individual family members of E2F mRNA expression for overall survival (OS) was evaluated by using online Kaplan–Meier Plotter (KM Plotter) database. Our result demonstrated that high expressions of three family members of E2F (E2F1, E2F3, E2F4) mRNA were significantly associated with unfavourable OS in all GC patients. However, increased expressions of E2F2, E2F5, E2F6 and E2F7 were significantly associated with favourable OS, especially for higher clinical stages in GC patients. These results provided a better insight into the prognostic functions of E2F mRNA genes in GC. Although the results should be further verified in clinical trials, our findings may be a favourable prognostic predictor for the development of newer therapeutic drugs in the treatment of GC.

scholarly journals Bioinformatics analysis identifies COL1A1, THBS2 and SPP1 as potential predictors of patient prognosis and immunotherapy response in gastric cancer

2020 ◽  
Author(s):  
Yali Wang ◽  
Kun Zheng ◽  
Xiuqiong Chen ◽  
Rui Chen ◽  
Yanmei Zou
Keyword(s):  
Gastric Cancer ◽  
Prognostic Significance ◽  
Cancer Prognosis ◽  
Clinicopathological Parameters ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Kegg Pathways ◽  
Ppi Networks ◽  
Kaplan Meier ◽  
Predictive Role

Background This study aimed to use bioinformatics tools to explore pivotal genes associated with the occurrence of gastric cancer (GC) and assess their prognostic significance, and link with clinicopathological parameters. We also investigated the predictive role of COL1A1, THBS2, and SPP1 in immunotherapy. Materials and methods We identified differential genes (DEGs) that were up- and down-regulated in the three datasets (GSE26942, GSE13911, and GSE118916) and created protein-protein interaction (PPI) networks from the overlapping DEGs. We then investigated the potential functions of the hub genes in cancer prognosis using PPI networks, and explored the influence of such genes in the immune environment. Results Overall, 268 overlapping DEGs were identified, of which 230 were up-regulated and 38 were down-regulated. CytoHubba selected the top ten hub genes, which included SPP1, TIMP1, SERPINE1, MMP3, COL1A1, BGN, THBS2, CDH2, CXCL8, and THY1. With the exception of SPP1, survival analysis using the Kaplan-Meier database showed that the levels of expression of these genes were associated with overall survival. Genes in the most dominant module explored by MCODE, COL1A1, THBS2, and SPP1, were primarily enriched for two KEGG pathways. Further analysis showed that all three genes could influence clinicopathological parameters and immune microenvironment, and there was a significant correlation between COL1A1, THBS2, SPP1, and PD-L1 expression, thus indicating a potential predictive role for GC response to immunotherapy. Conclusion ECM-receptor interactions and focal adhesion pathways are of great significance in the progression of GC. COL1A1, THBS2 and SPP1 may help predict immunotherapy response in GC patients.

Amplification and expression of c-MET correlate with poor prognosis of patients with gastric cancer and upregulate the expression of PDL1

2021 ◽  
Vol 53 (5) ◽  
pp. 547-557
Author(s):  
Ya’nan Yang ◽  
Chenchen Wang ◽  
Congqi Dai ◽  
Xinyang Liu ◽  
Wenhua Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Positive Association ◽  
Her2 Positive ◽  
Kaplan Meier ◽  
Met Amplification ◽  
Amplification Rate ◽  
Cox Proportional Hazard Regression

Abstract The prognostic significance of c-MET in gastric cancer (GC) remains uncertain. In the present study, we examined the amplification, expression, and the prognostic value of c-MET, human epidermal growth factor receptor 2 (HER2), and programmed cell death 1 ligand 1 (PDL1), together with the correlations among them in a large cohort of Chinese samples. A total of 444 patients were included. The immunohistochemistry (IHC) and the dual-color silver in situ hybridization (SISH) were performed to examine their expression and amplification. Univariate and multivariate analyses were performed by the Cox proportional hazard regression model, and survival curves were estimated by the Kaplan–Meier method. The positivity determined by IHC of c-MET was 24.8%, and the MET amplification rate was 2.3%. The positivity rates of HER2 and PDL1 were 8% and 34.7%, respectively. PDL1 expression had a significantly positive association with c-MET expression. c-MET positivity played a significant prognostic role in disease-free survival (DFS) (P = 0.032). Patients with mesenchymal-epithelial transition (MET) amplification had significantly poorer prognosis on both DFS and overall survival (OS). Subgroup analysis showed that in HER2-negative patients, but not in HER2-positive patients, MET-positive patients had significantly worse DFS (P = 0.000) and OS (P = 0.006). c-MET regulated the expression of PDL1 through an AKT-dependent pathway. c-MET inhibitor enhanced the T-cell killing ability and increased the efficacy of PD1 antibody. c-MET was found to be an independent prognostic factor for DFS of GC patients. A combination of c-MET inhibitors and PD1 antibodies could enhance the killing capacity of T cells, providing a preliminary basis for the clinical research on the same combination in GC treatment.

scholarly journals miR-21 Is a Promising Novel Biomarker for Lymph Node Metastasis in Patients with Gastric Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Yuejuan Xu ◽  
Jue Sun ◽  
Jianhua Xu ◽  
Qi Li ◽  
Yuewu Guo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Malignant Disease ◽  
Close Association ◽  
Survival Rates ◽  
Expression Level ◽  
Human Gastric Cancer ◽  
Node Metastasis ◽  
Kaplan Meier

Background. Gastric cancer (GC) is an important malignant disease around the world. Abnormalities of microRNAs (miRNAs) have been implicated in carcinogenesis of various cancers. In the present study, we examined miR-21 expression in human gastric cancer with lymph node metastasis and attempted to uncover its relationship with clinicopathologic data, especially with lymph node metastasis.Materials and Methods. The expression levels of miR-21 in the tumor specimens of GC patients were quantified by RT-PCR. The correlation between miR-21 level and multiple clinicopathological factors was then examined by Mann-Whitney test, Kaplan-Meier survival analysis, and operating characteristic (ROC) analysis.Results. The expression level of miR-21 was higher in GC patients with lymph node metastasis than in those without lymph node metastasis (P<0.05). Expression level of miR-21 was significantly correlated with histologic type, T stage, lymph node metastasis and pTNM stage. The overall survival rates in GC patients with low upregulated miR-21 expression were significantly higher than those with high upregulated miR-21 (P<0.05).Conclusion. A close association is implicated between the elevated miR-21and lymph node metastasis, which could potentially be exploited as a practical biomarker for lymph node metastasis in patients with GC.

Dysregulation of ECRG4 is associated with malignant properties and of prognostic importance in human gastric cancer

2021 ◽  
pp. 1-12
Author(s):  
Yanjie You ◽  
Shengjuan Hu
Keyword(s):  
Gastric Cancer ◽  
Prognostic Significance ◽  
Statistical Analyses ◽  
Human Gastric Cancer ◽  
Advanced Tumor Stage ◽  
Protein Levels ◽  
Cancer Pathogenesis ◽  
Advanced Tumor ◽  
Cancer Tissues ◽  
The Impact

BACKGROUND: We have previously characterized esophageal carcinoma-related gene 4 (ECRG4) as a novel tumor suppressor gene, which is frequently inactivated in nasopharyngeal carcinoma and breast cancer. Nevertheless, the expression status and prognostic significance of ECRG4 maintain elusive in human gastric cancer. Herein, we examined ECRG4 expression profile in gastric cancer and assessed its association with clinicopathological characteristics and patient survival. METHODS: Online data mining, real-time RT-PCR and immunohistochemistry were employed to determined ECRG4 expression at transcriptional and protein levels in tumors vs. noncancerous tissues. Statistical analyses including the Kaplan-Meier survival analysis and the Cox hazard model were utilized to detect the impact on clinical outcome. Moreover, ECRG4 expression was silenced in gastric cancer SGC7901 cells, and cell proliferation, colony formation and invasion assays were carried out. RESULTS: ECRG4 mRNA and protein levels were obviously downregulated in cancer tissues than noncancerous tissues. Statistical analyses demonstrated that low ECRG4 expression was found in 34.5% (58/168) of primary gastric cancer tissues, which was associated with higher histological grade (P= 0.018), lymph node metastasis (P= 0.011), invasive depth (P= 0.020), advanced tumor stage (P= 0.002) and poor overall survival (P< 0.001). Multivariate analysis showed ECRG4 expression is an independent prognostic predictor (P< 0.001). Silencing ECRG4 expression promoted gastric cancer cell growth and invasion. Western blot analysis revealed the anti-metastatic functions of ECRG4 by downregulating of E-cadherin and α-Catenin, as well as upregulating N-cadherin and Vimentin. CONCLUSIONS: Our observations reveal that ECRG4 expression is involved in gastric cancer pathogenesis and progression, and may serve as a candidate prognostic biomarker for this disease.

Expression and Clinical Significance of Serum Exosomal miR-375 in Patients with Gastric Cancer

2021 ◽  
Vol 7 (5) ◽  
pp. 3896-3904
Author(s):  
Daoting Deng ◽  
Hong Zhang ◽  
Junxi Liu ◽  
Lina Ma ◽  
Xinrui Lei ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Cox Regression Analysis ◽  
Healthy Group ◽  
Cancer Group ◽  
Kaplan Meier ◽  
Gastric Cancer Patients ◽  
Gastric Cancer Group

To explore exosomal miR-375 expression in gastric cancer patients and its relationship with patient prognosis. A total of 53 patients diagnosed with gastric cancer in our hospital from May 2014 to May 2016 were included as the gastric cancer group, and 46 healthy women who came to our hospital for physical examination during the same period were enrolled as the healthy group. Exosomal miR-375 expression level was detected using qRT-PCR, and the diagnostic performance and prognostic significance of exosomal miR-375 in gastric cancer were explored. The gastric cancer group showed increased exosomal miR-375 expression than the healthy group (P< 0.05); Kaplan-Meier survival analysis exhibited that serum exosomal miR-375 has an AUC of 0.778, sensitivity of 69.57%, and specificity of 75.47%, whereas Cox regression analysis showed that the miR-375 expression in exosomes was an independent risk factor affecting the prognosis of gastric cancer patients (P< 0.05). Patient with gastric cancer showed upregulated miR-375 expression in serum exosomes. Serum exosomal miR-375 was found to has positive sensitivity and specificity in the diagnosis of gastric cancer, which may be associated with poor prognosis of gastric cancer patients.

scholarly journals HER-2 Expression in Immunohistochemistry Has No Prognostic Significance in Gastric Cancer Patients

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Agnieszka Halon ◽  
Piotr Donizy ◽  
Przemyslaw Biecek ◽  
Julia Rudno-Rudzinska ◽  
Wojciech Kielan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Test Score ◽  
Prognostic Significance ◽  
Clinicopathological Parameters ◽  
Prognostic Impact ◽  
Curative Surgery ◽  
Regional Lymph Nodes ◽  
Poorly Differentiated ◽  
Her 2 ◽  
Gastric Cancer Patients

The role of HER-2 expression as a prognostic factor in gastric cancer (GC) is still controversial. The aim of the study was to asses HER-2 status, its correlations with clinicopathological parameters, and prognostic impact in GC patients. Tumor samples were collected from 78 patients who had undergone curative surgery. In order to evaluate the intensity of immunohistochemical (IHC) reactions two scales were applied: the immunoreactive score according to Remmele modified by the authors and standardised Hercep test score modified for GC by Hofmann et al. The HER-2 overexpression was detected by IHC in 23 (29.5%) tumors in Hercep test (score 2+/3+) and in 24 (30.7%) in IRS scale (IRS 4–12). The overexpression of HER-2 was associated with poorly differentiated tumors, but this correlation was not significant (P=0.064). No relationship was found between HER-2 expression and primary tumor size and degree of spread to regional lymph nodes. Both univariate and multivariate analyses revealed that TNM stage and patient’s age were the crucial negative prognostic factors. No correlation was observed between patient survival and expression of HER-2 estimated using both scales. This research did not confirm HER-2 expression (evaluated with immunohistochemistry) value as a prognostic tool in GC.

scholarly journals Prognostic and immunological value of LTB4R in pan-cancer

2021 ◽  
Vol 18 (6) ◽  
pp. 9336-9356
Author(s):  
Sidan Long ◽  
◽  
Shuangshuang Ji ◽  
Kunmin Xiao ◽  
Peng Xue ◽  
...  
Keyword(s):  
Immune Cells ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
Negative Influence ◽  
Leukotriene B4 ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Immune Infiltration ◽  
Significant Difference ◽  
Pan Cancer

<abstract> <sec><title>Background</title><p>LTB4 receptor 1 (LTB4R), as the high affinity leukotriene B4 receptor, is rapidly revealing its function in malignancies. However, it is still uncertain.</p> </sec> <sec><title>Methods</title><p>We investigated the expression pattern and prognostic significance of LTB4R in pan-cancer across different databases, including ONCOMINE, PrognoScan, GEPIA, and Kaplan-Meier Plotter, in this study. Meanwhile, we explored the significance of LTB4R in tumor metastasis by HCMDB. Then functional enrichment analysis of related genes was performed using GeneMANIA and DAVID. Lastly, utilizing the TIMER datasets, we looked into the links between LTB4R expression and immune infiltration in malignancies.</p> </sec> <sec><title>Results</title><p>In general, tumor tissue displayed higher levels of LTB4R expression than normal tissue. Although LTB4R had a negative influence on pan-cancer, a high expression level of LTB4R was protective of LIHC (liver hepatocellular carcinoma) patients' survival. There was no significant difference in the distribution of LTB4R between non-metastatic and metastatic tumors. Based on Gene Set Enrichment Analysis, LTB4R was implicated in pathways involved in inflammation, immunity, metabolism, and cancer diseases. The correlation between immune cells and LTB4R was found to be distinct across cancer types. Furthermore, markers of infiltrating immune cells, such as Treg, T cell exhaustion and T helper cells, exhibited different LTB4R-related immune infiltration patterns.</p> </sec> <sec><title>Conclusion</title><p>The LTB4R is associated with immune infiltrates and can be used as a prognostic biomarker in pan-cancer.</p> </sec> </abstract>

scholarly journals Prognostic Significance of NBEAL2 in Liver hepatocellular carcinoma

2021 ◽  
Author(s):  
Yanghui Wen ◽  
Hui Su ◽  
Wuke Wang ◽  
Feng Ren ◽  
Haitao Jiang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
The Cancer Genome Atlas ◽  
Clinicopathological Parameters ◽  
Chi Square ◽  
Kaplan Meier ◽  
Chi Square Test ◽  
Liver Hepatocellular Carcinoma ◽  
The Relationship

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.

Prognostic value of biglycan in gastric cancer

2020 ◽  
Author(s):  
Sizhe Hu ◽  
Peipei Li ◽  
Chenying Wang ◽  
Xiyong Liu
Keyword(s):  
Gastric Cancer ◽  
Transcription Factors ◽  
Poor Prognosis ◽  
Prognostic Significance ◽  
Bioinformatic Analysis ◽  
Gene Set Enrichment Analysis ◽  
High Expression ◽  
Mrna Levels ◽  
Gene Signatures ◽  
Kaplan Meier

Abstract Background: BGN (biglycan) is a family member of small leucine-rich repeat proteoglycans. High expression of BGN might enhance the invasion and metastasis in some types of tumors. Here, the prognostic significance of BGN was evaluated in gastric cancer.Material and Methods: Two independent Gene Expression Omnibus (GEO) gastric cancer microarray datasets( n= 64, n=432) were collected for this study. Kaplan-Meier analysis was applied to evaluate if BGN impacts the outcomes of gastric cancer. The gene set enrichment analysis (GSEA) was used to explore BGN and cancer-related gene signatures. Bioinformatic analysis predicted the putative transcription factors of BGN.Results: For gastric cancer, the mRNA expression level of BGN in tumor tissues was significantly higher than that in normal tissues. Kaplan-Meier analysis showed that higher expression of BGN mRNA was significantly associated with more reduced recurrence-free survival (RFS). GSEA results suggested that BGN significantly enriched metastasis and poor prognosis gene signatures, revealing that BGN might be associated with cell proliferation, poor differentiation, high invasiveness of gastric cancer. Meanwhile, the putative transcription factors, including AR, E2F1, and TCF4, weres predicted by bioinformatic analysis and also significantly correlated with expression of BGN in mRNA levels. Conclusion: High expression of BGN mRNA was significantly related to poor prognosis, which suggested BGN was a potential prognostic biomarker and therapeutic target of gastric cancer.

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