High Expression of EIF4G2 Mediated By the TUG1/hsa-miR-26a-5p Axis Is Associated With Poor Prognosis and Immune Infiltration of Gastric Cancer

Abstract Background: Eukaryotic translation initiation factor 4 gamma 2 (EIF4G2) is involved in the occurrence and development of various tumors. However, the effect of EIF4G2 in gastric cancer (GC) has not been fully explored. The purpose of this study was to explore the function and mechanism of EIF4G2 in GC.Methods: The Tumor Immune Estimation Resource 2.0 database was used to analyze EIF4G2 expression in various cancers and the relationship between EIF4G2 expression and tumor-infiltrating immune cells. Gene Expression Profiling Interactive Analysis was utilized to assess the EIF4G2 expression level and its effect on survival in GC. UALCAN was conducted to analyze EIF4G2 expression in various sub-groups of GC. The Kaplan–Meier plotter was employed for survival analysis. Receiver Operator Characteristic (ROC) curve analysis was applied to evaluate the diagnostic role of EIF4G2 in GC. LinkedOmics was used to identify the co-expressed genes and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. The Tumor-Immune System Interaction database was employed to analyze the correlation between EIF4G2 expression and tumor-infiltrating lymphocytes. The starBase web platform was used to predict the upstream microRNAs and long non-coding RNAs.Results: EIF4G2 expression was upregulated in GC tissues compared to normal controls. High expression of EIF4G2 indicated poor prognosis in GC. ROC analysis revealed that EIF4G2 had good diagnostic ability to distinguish GC from normal tissues. Immune infiltration analysis indicated that EIF4G2 expression may be involved in the modulation of tumor immune infiltration in GC. Finally, we determined that the Taurine Up-Regulated 1 (TUG1)/hsa-miR-26a-5p/EIF4G2 axis was the most likely regulatory pathway involved in GC development.Conclusions: EIF4G2 was upregulated in GC and elevated expression of EIF4G2 indicated unfavorable prognosis. Moreover, EIF4G2 expression may be involved in the regulation of tumor immune cell infiltration. The TUG1/hsa-miR-26a-5p axis is a likely upstream regulatory mechanism of EIF4G2 in GC. EIF4G2 may thus serve as a prognosis biomarker and present a new therapeutic target.

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Upregulated CCNE1 Correlates with Poor Prognosis, Tumor Immune Infiltration and Escape in Breast Cancer

10.21203/rs.3.rs-966772/v1 ◽

2021 ◽

Author(s):

Jiaxi Feng ◽

Yanan Hu ◽

Dan Liu ◽

Shanshan Wang ◽

Mengci Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Immune Cells ◽

Poor Prognosis ◽

Immune Cell ◽

High Expression ◽

Expression Level ◽

Immune Cell Infiltration ◽

Immune Infiltration ◽

Kaplan Meier ◽

Kaplan Meier Plotter

Abstract Background Breast cancer (BC) is the most common malignant tumor in women and widely known for its poor prognosis. More and more research has discovered that cyclin E1 (CCNE1) plays an important role in progression of various types of cancer. But its specific mechanism in BC progression still needs further research to explore.Methods At first, we determined the expression and prognostic value of CCNE1 through The Cancer Genome Atlas (TCGA) database and The Genotype-Tissue Expression (GTEx) data. Then, we predicted the upstream non-coding RNAs of CCNE1 through StarBase, GEPIA, and Kaplan-Meier plotter database. We further studied the correlation of CCNE1 expression with BC immune cell infiltration, biomarkers of immune cells and immune checkpoints expression through TIMER and GEPIA databases.Results The results suggested that CCNE1 was significantly upregulated in BC and its high expression was correlated with poor prognosis in BC patients. Next, we identified long noncoding RNA (lncRNA) LINC00511 / microRNA-195-5p (miR-195-5p) / CCNE1 axis as the most potential pathway that could regulate CCNE1 expression in BC through StarBase, GEPIA, and Kaplan-Meier plotter database. Furthermore, our in-depth research discovered that CCNE1 expression level was significantly correlated with tumor immune cell inﬁltration, biomarkers of immune cells, and immune checkpoint expression in BC. conclusions In summary, high expression level of CCNE1 was significantly correlated with poor prognosis, tumor immune infiltration and escape in BC.

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Upregulated CCNE1 Correlates with Poor Prognosis, Tumor Immune Infiltration and Escape in Breast Cancer

10.21203/rs.3.rs-966772/v2 ◽

2021 ◽

Author(s):

Jiaxi Feng ◽

Yanan Hu ◽

Dan Liu ◽

Shanshan Wang ◽

Mengci Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Immune Cells ◽

Poor Prognosis ◽

Immune Cell ◽

High Expression ◽

Expression Level ◽

Immune Cell Infiltration ◽

Immune Infiltration ◽

Kaplan Meier ◽

Kaplan Meier Plotter

Abstract BackgroundBreast cancer (BC) is the most common malignant tumor in women and widely known for its poor prognosis. More and more research has discovered that cyclin E1 (CCNE1) plays an important role in progression of various types of cancer. But its specific mechanism in BC progression still needs further research to explore.MethodsAt first, we determined the expression and prognostic value of CCNE1 through The Cancer Genome Atlas (TCGA) database and The Genotype-Tissue Expression (GTEx) data. Then, we predicted the upstream non-coding RNAs of CCNE1 through StarBase, GEPIA, and Kaplan-Meier plotter database. We further studied the correlation of CCNE1 expression with BC immune cell infiltration, biomarkers of immune cells and immune checkpoints expression through TIMER and GEPIA databases.ResultsThe results suggested that CCNE1 was significantly upregulated in BC and its high expression was correlated with poor prognosis in BC patients. Next, we identified long noncoding RNA (lncRNA) LINC00511 / microRNA-195-5p (miR-195-5p) / CCNE1 axis as the most potential pathway that could regulate CCNE1 expression in BC through StarBase, GEPIA, and Kaplan-Meier plotter database. Furthermore, our in-depth research discovered that CCNE1 expression level was significantly correlated with tumor immune cell inﬁltration, biomarkers of immune cells, and immune checkpoint expression in BC.ConclusionIn summary, high expression level of CCNE1 was significantly correlated with poor prognosis, tumor immune infiltration and escape in BC.

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High expression of eIF4E is associated with tumor macrophage infiltration and leads to poor prognosis in breast cancer

BMC Cancer ◽

10.1186/s12885-021-09010-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Fan Li ◽

Huizhi Sun ◽

Yue Li ◽

Xiaoyu Bai ◽

Xueyi Dong ◽

...

Keyword(s):

Breast Cancer ◽

Immune Cells ◽

Poor Prognosis ◽

Prognostic Value ◽

Translation Initiation Factor ◽

Functional Enrichment ◽

Macrophage Infiltration ◽

Initiation Factor ◽

Migration And Invasion ◽

Immune Infiltration

Abstract Background The expression and activation of eukaryotic translation initiation factor 4E (eIF4E) is associated with cell transformation and tumor initiation, but the functional role and the mechanism whereby it drives immune cell infiltration in breast cancer (BRCA) remain uncertain. Methods Oncomine, Timer and UALCAN were used to analyze the expression of eIF4E in various cancers. PrognoScan, Kaplan–Meier plotter, and GEPIA were utilized to analyze the prognostic value of eIF4E in select cancers. In vitro cell experiments were used to verify the role of eIF4E in promoting the progression of BRCA. ImmuCellAI and TIMER database were used to explore the relationship between eIF4E and tumor infiltrating immune cells. The expression of a macrophage marker (CD68+) and an M2-type marker (CD163+) was evaluated using immunohistochemistry in 50 invasive BRCA samples on tissue microarrays. The Human Protein Atlas (HPA) database was used to show the expression of eIF4E and related immune markers. LinkedOmics and NetworkAnalyst were used to build the signaling network. Results Through multiple dataset mining, we found that the expression of eIF4E in BRCA was higher than that in normal tissues, and patients with increased eIF4E expression had poorer survival and a higher cumulative recurrence rate in BRCA. At the cellular level, BRCA cell migration and invasion were significantly inhibited after eIF4E expression was inhibited by siRNA. Immune infiltration analysis showed that the eIF4E expression level was significantly associated with the tumor purity and immune infiltration levels of different immune cells in BRCA. The results from immunohistochemical (IHC) staining further proved that the expression of CD68+ and CD163+ were significantly increased and correlated with poor prognosis in BRCA patients (P < 0.05). Finally, interaction network and functional enrichment analysis revealed that eIF4E was mainly involved in tumor-related pathways, including the cell adhesion molecule pathway and the JAK-STAT signaling pathway. Conclusions Our study has demonstrated that eIF4E expression has prognostic value for BRCA patients. eIF4E may act as an essential regulator of tumor macrophage infiltration and may participate in macrophage M2 polarization.

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ncRNAs-mediated high expression of SEMA3F correlates with poor prognosis and tumor immune infiltration of hepatocellular carcinoma

Molecular Therapy — Nucleic Acids ◽

10.1016/j.omtn.2021.03.014 ◽

2021 ◽

Author(s):

Weiyang Lou ◽

Wenlong Wang ◽

Jing Chen ◽

Shuqian Wang ◽

Yuan Huang

Keyword(s):

Hepatocellular Carcinoma ◽

Poor Prognosis ◽

High Expression ◽

Immune Infiltration

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Expression of LOX Suggests Poor Prognosis in Gastric Cancer

Frontiers in Medicine ◽

10.3389/fmed.2021.718986 ◽

2021 ◽

Vol 8 ◽

Author(s):

Jinfeng Zhu ◽

Chen Luo ◽

Jiefeng Zhao ◽

Xiaojian Zhu ◽

Kang Lin ◽

...

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Logistic Regression ◽

Regression Analysis ◽

Poor Prognosis ◽

Cox Regression ◽

Gene Set Enrichment Analysis ◽

High Expression ◽

Expression Level ◽

Cox Regression Analysis

Background: Lysyl oxidase (LOX) is a key enzyme for the cross-linking of collagen and elastin in the extracellular matrix. This study evaluated the prognostic role of LOX in gastric cancer (GC) by analyzing the data of The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) dataset.Methods: The Wilcoxon rank-sum test was used to calculate the expression difference of LOX gene in gastric cancer and normal tissues. Western blot and immunohistochemical staining were used to evaluate the expression level of LOX protein in gastric cancer. Kaplan-Meier analysis was used to calculate the survival difference between the high expression group and the low expression group in gastric cancer. The relationship between statistical clinicopathological characteristics and LOX gene expression was analyzed by Wilcoxon or Kruskal-Wallis test and logistic regression. Univariate and multivariate Cox regression analysis was used to find independent risk factors affecting the prognosis of GC patients. Gene set enrichment analysis (GSEA) was used to screen the possible mechanisms of LOX and GC. The CIBERSORT calculation method was used to evaluate the distribution of tumor-infiltrating immune cell (TIC) abundance.Results: LOX is highly expressed in gastric cancer tissues and is significantly related to poor overall survival. Wilcoxon or Kruskal-Wallis test and Logistic regression analysis showed, LOX overexpression is significantly correlated with T-stage progression in gastric cancer. Multivariate Cox regression analysis on TCGA and GEO data found that LOX (all p < 0.05) is an independent factor for poor GC prognosis. GSEA showed that high LOX expression is related to ECM receptor interaction, cancer, Hedgehog, TGF-beta, JAK-STAT, MAPK, Wnt, and mTOR signaling pathways. The expression level of LOX affects the immune activity of the tumor microenvironment in gastric cancer.Conclusion: High expression of LOX is a potential molecular indicator for poor prognosis of gastric cancer.

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High expression of GNB4 predicts poor prognosis in patients with Helicobacter pylori-positive advanced gastric cancer

Translational Cancer Research ◽

10.21037/tcr-19-2914 ◽

2020 ◽

Vol 9 (7) ◽

pp. 4224-4238

Author(s):

Jianpeng Gao ◽

Teng Yu ◽

Yi Xuan ◽

Zhenglun Zhu

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Advanced Gastric Cancer ◽

Poor Prognosis ◽

High Expression

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Prognostic value of biglycan in gastric cancer

10.21203/rs.3.rs-103093/v1 ◽

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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Understanding and Targeting the Eukaryotic Translation Initiation Factor eIF4E in Head and Neck Cancer

Journal of Oncology ◽

10.1155/2009/981679 ◽

2009 ◽

Vol 2009 ◽

pp. 1-12 ◽

Cited By ~ 29

Author(s):

Biljana Culjkovic ◽

Katherine L. Borden

Keyword(s):

Translation Initiation ◽

Poor Prognosis ◽

Suicide Gene ◽

Translation Initiation Factor ◽

Initiation Factor ◽

Human Leukemia ◽

Eukaryotic Translation Initiation Factor ◽

Eukaryotic Translation ◽

Eukaryotic Translation Initiation ◽

Clinical Responses

The eukaryotic translation initiation factor eIF4E is elevated in about 30% of human malignancies including HNSCC where its levels correlate with poor prognosis. Here, we discuss the biochemical and molecular underpinnings of the oncogenic potential of eIF4E. Studies in human leukemia specimens, and later in a mouse model of prostate cancer, strongly suggest that cells with elevated eIF4E develop an oncogene dependency to it, making them more sensitive to targeting eIF4E than normal cells. We describe several strategies that have been suggested for eIF4E targeting in the clinic: the use of a small molecule antagonist of eIF4E (ribavirin), siRNA or antisense oligonucleotide strategies, suicide gene therapy, and the use of a tissue-targeting 4EBP fusion peptide. The first clinical trial targeting eIF4E indicates that ribavirin effectively targets eIF4E in poor prognosis leukemia patients and more importantly leads to striking clinical responses including complete and partial remissions. Finally, we discuss the relevance of these findings to HNSCC.

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