Diagnostic and prognostic value of HOXC family members in gastric cancer

2021 ◽  
Author(s):  
Mei-Qian Wang ◽  
Qi-Yun Yin ◽  
Yi-Ru Chen ◽  
Sen-Lin Zhu
Keyword(s):  
Gastric Cancer ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Family Members ◽  
Enrichment Analysis ◽  
Diagnostic Value ◽  
Gene Set Enrichment Analysis ◽  
Gene Set Enrichment ◽  
Hox Clusters ◽  
Diagnostic And Prognostic Value

Aims: HOX clusters encode proteins that play pivotal roles in regulating transcription factors and many other proteins during embryogenesis. However, little is known about the diagnostic and prognostic values of HOXC family members in gastric cancer (GC). Materials and methods: The authors evaluated the data in patients with GC based on bioinformatics analysis. Results: HOXC6/8/9/10/11/13 were overexpressed in GC and associated with a poor prognosis. HOXC4/5 were downregulated in GC tissues. Receiver operating characteristic curve analysis demonstrated that they have high diagnostic value. In addition, HOXC4/5/6/9/10/11/13 were negatively correlated with DNA methylation level. The gene set enrichment analysis results implied that they play essential roles in multiple biological processes underlying tumorigenesis. Conclusion: HOXC family members are potential targets for diagnosis and may work as prognostic biomarkers of GC.

scholarly journals Infiltration of Immunoinflammatory Cells and Related Chemokine/Interleukin Expression in Different Gastric Immune Microenvironments

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Ang Wang ◽  
Siru Nie ◽  
Zhi Lv ◽  
Jing Wen ◽  
Yuan Yuan
Keyword(s):  
Gastric Cancer ◽  
Gastric Mucosa ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Upward Trend ◽  
Immune Microenvironment ◽  
Gene Set Enrichment ◽  
Expression Characteristic ◽  
Precancerous Stage

Gastric mucosal immune microenvironment plays an important role in the occurrence and development of diseases such as inflammation and cancer. In the present study, single-sample gene set enrichment analysis (ssGSEA) was used to evaluate the expression of cytokines and the degree of immune cell infiltration in four different gastric mucosa tissues from normal gastric mucosa, simple gastritis, and atrophic gastritis to gastric cancer. Here, we show the immune microenvironments of these four gastric mucosae were significantly different. From inflammation to gastric cancer, most immunoinflammatory cells showed a downward trend such as central memory CD4 T cell. Instead, several cells showed an upward trend such as macrophage. Additionally, we found some chemokines/interleukins were illustrated to be low expressed (or highly expressed) in precancerous stage and highly expressed (or low expressed) in postcancerous stage, which demonstrated an opposite expression characteristic in pre-/postcancerous stage.

scholarly journals Expression Profiles and Prognostic Values of BOLA Family members in Ovarian Cancer

2020 ◽  
Author(s):  
Mingyang Zhu ◽  
Shiqi Xiao
Keyword(s):  
Ovarian Cancer ◽  
Metal Ion ◽  
Expression Profiles ◽  
Family Members ◽  
Enrichment Analysis ◽  
Genetic Alterations ◽  
Gene Set Enrichment Analysis ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Protein Disulfide Oxidoreductase

Abstract Background: The BOLA gene family, comprising 3 members, is mainly involved in the regulation of intracellular iron homeostasis. Emerging evidence suggests that BOLA family member 2 play vital roles in tumorigenesis and progression of hepatic cellular carcinoma. However, little known about its roles in ovarian cancer. Methods: In present study, we investigated the expression profiles, prognostic roles, and genetic alterations of three BOLA family members in patients with ovarian cancer through several public databases, containing Oncomine and Gene Expression Profiling Interactive Analysis, Human Protein Atlas, Kaplan–Meier plotter and cBioPortal. Then, we constructed the protein–protein interaction networks of BOLA proteins and their interactors by using String database and Cytoscape software. In addition, we performed the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment by the Annotation, Visualization, and Integrated Discovery database. Finally, we explored the mechanisms underlying the involvement of BOLA family members in OC by using gene set enrichment analysis. Results: The mRNA and protein expression levels of BOLA2 and BOLA3 were heavily higher in ovarian cancer tissues than that in normal ovarian tissues. Dysregulated mRNA expressions of three BOLA family members were significantly associated with prognosis in overall or subgroup analysis. Moreover, genetic alterations also occurred in three BOLA family members in ovarian cancer. Network analysis and enrichment analysis indicated that three BOLA family members and their 20 interactors were mainly associated with metal-ion binding and protein disulfide oxidoreductase activity. Gene set enrichment analysis indicated that BOLA family members were mainly associated with oxidative phosphorylation, proteasome, protein export and glutathione metabolism in ovarian cancer. Conclusions: In brief, the present comprehensive bioinformatics analysis revealed that BOLA1, 2, and 3 may be new prognostic biomarkers, and BOLA2 and BOLA3 may be a potential therapeutic target of precision therapy for patients with ovarian cancer, but further studies are demanded to certify this notion.

scholarly journals ANXA9 as a novel prognostic biomarker associated with immune infiltrates in gastric cancer

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12605
Author(s):  
Tongtong Zhang ◽  
Suyang Yu ◽  
Shipeng Zhao
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Survival Curve ◽  
Enrichment Analysis ◽  
Prognostic Indicator ◽  
Diagnostic Value ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Clinicopathological Parameters ◽  
The Relationship

Background Gastric cancer (GC) is the most prevalent malignancy among the digestive system tumors. Increasing evidence has revealed that lower mRNA expression of ANXA9 is associated with a poor prognosis in colorectal cancer. However, the role of ANXA9 in GC remains largely unknown. Material and Methods The Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas databases were used to investigate the expression of ANXA9 in GC, which was then validated in the four Gene Expression Omnibus (GEO) datasets. The diagnostic value of ANXA9 for GC patients was demonstrated using a receiver operating characteristic (ROC) curve. The correlation between ANXA9 expression and clinicopathological parameters was analyzed in The Cancer Genome Atlas (TCGA) and UALCAN databases. The Kaplan-Meier (K-M) survival curve was used to elucidate the relationship between ANXA9 expression and the survival time of GC patients. We then performed a gene set enrichment analysis (GSEA) to explore the biological functions of ANXA9. The relationship of ANXA9 expression and cancer immune infiltrates was analyzed using the Tumor Immune Estimation Resource (TIMER). In addition, the potential mechanism of ANXA9 in GC was investigated by analyzing its related genes. Results ANXA9 was significantly up-regulated in GC tissues and showed obvious diagnostic value. The expression of ANXA9 was related to the age, gender, grade, TP53 mutation, and histological subtype of GC patients. We also found that ANXA9 expression was associated with immune-related biological function. ANXA9 expression was also correlated with the infiltration level of CD8+ T cells, neutrophils, and dendritic cells in GC. Additionally, copy number variation (VNV) of ANXA9 occurred in GC patients. Function enrichment analyses revealed that ANXA9 plays a role in the GC progression by interacting with its related genes. Conclusions Our results provide strong evidence of ANXA9 expression as a prognostic indicator related to immune responses in GC.

scholarly journals Expression profiles and prognostic values of BolA family members in ovarian cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Mingyang Zhu ◽  
Shiqi Xiao
Keyword(s):  
Ovarian Cancer ◽  
Metal Ion ◽  
Expression Profiles ◽  
Family Members ◽  
Enrichment Analysis ◽  
Genetic Alterations ◽  
Gene Set Enrichment Analysis ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Protein Disulfide Oxidoreductase

Abstract Background The BOLA gene family, comprising three members, is mainly involved in regulating intracellular iron homeostasis. Emerging evidence suggests that BolA family member 2 plays a vital role in tumorigenesis and hepatic cellular carcinoma progression. However, there was less known about its role in ovarian cancer. Methods In the present study, we investigated the expression profiles, prognostic roles, and genetic alterations of three BolA family members in patients with ovarian cancer through several public databases, containing Oncomine and Gene Expression Profiling Interactive Analysis, Human Protein Atlas, Kaplan–Meier plotter and cBioPortal. Then, we constructed the protein-protein interaction networks of BOLA proteins and their interactors by using the String database and Cytoscape software. In addition, we performed the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment by the Annotation, Visualization, and Integrated Discovery database. Finally, we explored the mechanisms underlying BolA family members’ involvement in OC by using gene set enrichment analysis. Results The mRNA and protein expression levels of BOLA2 and BOLA3 were heavily higher in ovarian cancer tissues than in normal ovarian tissues. Dysregulated mRNA expressions of three BolA family members were significantly associated with prognosis in overall or subgroup analysis. Moreover, genetic alterations also occurred in three BolA family members in ovarian cancer. GO analysis indicated that BolA family members might regulate the function of metal ion binding and protein disulfide oxidoreductase activity. Gene set enrichment analysis indicated that BolA family members were mainly associated with oxidative phosphorylation, proteasome, protein export, and glutathione metabolism in ovarian cancer. Conclusion In brief, our finding may contribute to increasing currently limited prognostic biomarkers and treatment options for ovarian cancer.

scholarly journals Mining the TCGA Database for Microenvironment‐Related Genes with Prognostic Value in Gastric Cancer

2021 ◽  
Author(s):  
Ting Liu ◽  
Zheng Gong ◽  
Hong Zhang ◽  
Yi Wan ◽  
Ming-Han Ren ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Distant Metastasis ◽  
Clinical Stage ◽  
Enrichment Analysis ◽  
Clinicopathological Characteristics ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Protein Protein Interaction

Abstract BackgroundGastric cancer (GC) is the fifth most common cancer worldwide. Previous studies have suggested that the tumor microenvironment (TME) plays an important role in the development and prognosis of GC. In this study, we aimed to identify genes in tumor-infiltrating immune cells (TICs) that influence the progression and prognosis of GC. MethodsWe used the ESTIMATE algorithm to calculate the scores of the stromal and immune components of the TME in 407 GC samples collected from The Cancer Genome Atlas (TCGA) database.The differentially expressed genes (DEGs) were intersected by a protein-protein interaction (PPI) network and analyzed by univariate Cox regression.Further analysis showed the correlation between MCEMP1 and the clinicopathological characteristics of GC patients (clinical stage, distant metastasis) and survival.Then we used Gene set enrichment analysis (GSEA) and CIBERSORT analysis to examine the relationship between MCEMP1 and the TME.ResultsThe analysis revealed that the expression of MCEMP1 was positively correlated with the clinicopathological characteristics of GC patients (clinical stage, distant metastasis) and negatively correlated with survival. Gene set enrichment analysis (GSEA) indicated that gene sets in the MCEMP1 high expression group were concentrated mainly in immune-related pathways. CIBERSORT analysis of the proportion of TICs revealed that neutrophils and M2 macrophages were positively correlated with MCEMP1 expression, suggesting that MCEMP1 is responsible for preservation of the immune-dominant status of the TME. ConclusionHigh MCEMP1 expression might be a biomarker of a poor prognosis in GC patients and provide a clue regarding the different statuses of the TME, offering additional insight into therapy for GC.

scholarly journals The Association of Sex-biased ATRX Mutation in Female Gastric Cancer Patients With Enhanced Immunotherapy-related Anticancer Immunity  

2020 ◽  
Author(s):  
You Ge ◽  
Feiran Wei ◽  
Guoping Du ◽  
Gaoqiang Fei ◽  
Wei Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Enrichment Analysis ◽  
Genetic Alterations ◽  
Gene Set Enrichment Analysis ◽  
Gene Set Enrichment ◽  
Female Patients ◽  
Male Patients ◽  
Ifn Γ ◽  
Sex Biases ◽  
Anticancer Immunity

Abstract Background: Genetic alterations have been proven to be the promising biomarkers for ICI response. However, sex biases in genetic alterations have been often ignored in the field of immunotherapy, which might specially influence the anticancer immunity and immunotherapy efficacy in male or female patients. Here, we have systematically evaluated the effect of the sex biases in somatic mutation of gastric cancer (GC) patients on the anticancer immunity and clinical benefit to immunotherapy. Methods: Genomic and transcriptomic data of gastric cancer were downloaded from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC). We also obtained the genomic and clinical data of a MSKCC ICI-treated cohort from cbioportal database. GC male and female-derived tumor somatic mutation profiles were compared by maftools R package. Single sample gene set enrichment analysis (ssGSEA) was conducted to calculate the score of the anticancer immunity indicators including IFN-γ signaling, cytolytic activity (CYT) and antigen presenting machinery (APM). Results: ATRX was found to mutate more frequently in female GC patients compared to male patients (FDR = 0.0108). Female GC patients with ATRX mutation manifested significantly more MSI-high subtypes, increased TMB and PDL1 expression as well as higher scores of IFN-γ signaling, CYT and APM. Gene set enrichment analysis (GSEA) has shown that ATRX mutation might enhance the immunogenicity and anticancer immunity through affecting DNA damage repair pathways. In the ICI-treated cohort from MSKCC, GC patients with ATRX mutation were associated with prolonged overall survival. When stratifying the entire ICI-treated cohort by sex, female patients with ATRX mutation obtained significantly better survival benefits than that of ATRX mutant male patients (Female patients, HR of ATRX MT vs WT = 0.636, 95%CI = 0.455-0.890, P = 0.023; Male patients, HR of ATRX MT vs WT = 0.929, 95%CI = 0.596-1.362, P = 0.712). Conclusions: ATRX mutation might serve as a potential predictive biomarker for favorable clinical benefit to ICI in female GC patients. ATRX mutation could be applied in combination with other biomarkers of ICI response to better identify the female GC patients who will derive greater benefits from ICI therapy.

scholarly journals Gastrin-17 Combined With CEA, CA12-5 and CA19-9 Improves the Sensitivity For the Diagnosis of Gastric Cancer

2021 ◽  
Author(s):  
Zhen Wang ◽  
Tang-ming Mo ◽  
Lei Tian ◽  
Jun-qiang Chen
Keyword(s):  
Gastric Cancer ◽  
Area Under Curve ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Diagnostic Value ◽  
Serum Markers ◽  
Control Group ◽  
Positive Rate ◽  
Healthy Control ◽  
Operating Characteristic Curve

Abstract Background: Previous studies reported the utility of serum tumor markers (such as CEA, CA12-5 and CA19-9) and gastrin-17 in the diagnosis of gastric cancer (GC). However, the value of these serum markers for diagnosing GC is still under debate.Methods: The level of CEA, CA12-5, CA19-9 and gastrin-17 was tested in 230 GC patients and 99 healthy people. The value of the four markers for diagnosing GC was analyzed.Results: The positive rate of Gastrin-17, CEA, CA199 and CA125 were much higher in GC group (22.61%, 22.61%, 20.00% and 8.26%, respectively) than that of healthy control group (5.05%, 2.02%, 1.01% and 2.02%, respectively). The sensitivity of Gastrin-17, CEA, CA125 and CA199 in the diagnosis of GC were 22.61%, 22.61%, 6.96% and 20.00%, respectively, and the corresponding specificity were 94.95%, 97.98%, 98.99% and 98.99%, respectively. By using the optimal cut-off value derived from the area under curve (AUC) of receiver operating characteristic curve, the AUC of gastin-17, CEA, CA125, CA199 increased to 0.72, 0.64, 0.61 and 0.65, respectively. After combining the four markers, the AUC increased to 0.79 (95% CI: 0.75-0.84), and the corresponding sensitivity and specificity were 65.22% (95% CI: 58.70% - 71.40%) and 84.85% (95% CI: 76.20% - 91.30%), respectively.Conclusion: CEA, CA12-5, CA19-9 and gastrin-17 were all valuable in the diagnosis of GC, and gastrin-17 had the best diagnostic value among the four markers. Gastrin-17 combined with CEA, CA12-5 and CA19-9 could improve the diagnostic value of GC significantly. Prospective, multi-center studies are needed to validate our findings.

scholarly journals HTRA3 Is a Prognostic Biomarker and Associated With Immune Infiltrates in Gastric Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Ce Ji ◽  
Li-Sha Sun ◽  
Fei Xing ◽  
Nan Niu ◽  
Hong-Li Gao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Multivariate Analysis ◽  
Confidence Interval ◽  
Enrichment Analysis ◽  
Hazard Ratio ◽  
Gene Set Enrichment Analysis ◽  
Signal Pathways ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
The Impact

HtrA serine peptidase 3 (HTRA3) participates in multiple signal pathways and plays an important regulatory role in various malignancies; however, its role on prognosis and immune infiltrates in gastric cancer (GC) remains unclear. The study investigated HTRA3 expression in tumor tissues and its association with immune infiltrates, and determined its prognostic roles in GC patients. Patients with GC were collected from the cancer genome atlas (TCGA). We compared the expression of HTRA3 in GC and normal gastric mucosa tissues with Wilcoxon rank sum test. And logistic regression was used to evaluate the relationship between HTRA3 and clinicopathological characters. Gene ontology (GO) term analysis, Gene set enrichment analysis (GSEA), and single-sample Gene Set Enrichment Analysis (ssGSEA) was conducted to explain the enrichmental pathways and functions and quantify the extent of immune cells infiltration for HTRA3. Kaplan-Meier analysis and Cox regression were performed to evaluate the correlation between HTRA3 and survival rates. A nomogram, based on Cox multivariate analysis, was used to predict the impact of HTRA3 on prognosis. High HTRA3 expression was significantly correlated with tumor histological type, histological grade, clinical stage, T stage, and TP53 status (P < 0.05). HTRA3-high GC patients had a lower 10-year progression-free interval [PFI; hazard ratio (HR): 1.46; 95% confidence interval (CI): 1.02–2.08; P = 0.038], disease-specific survival (DSS; HR: 1.65; CI: 1.08–2.52; P = 0.021) and overall survival (OS; HR: 1.59; CI: 1.14–2.22; P = 0.006). Multivariate survival analysis showed that HTRA3 was an independent prognostic marker for PFI (HR: 1.456; CI: 1.021–2.078; P = 0.038), DSS (HR: 1.650; CI: 1.079–2.522; P = 0.021) and OS [hazard ratio (HR): 1.590; 95% confidence interval (CI):1.140–2.219; P = 0.006]. The C-indexes and calibration plots of the nomogram based on multivariate analysis indicated an effective predictive performance for GC patients. GSEA showed that High HTRA3 expression may activate NF-κB pathway, YAP1/WWTR1/TAZ pathway, and TGFβ pathway. There was a negative correlation between the HTRA3 expression and the abundances of adaptive immunocytes (T helper cell 17 cells) and a positive correlation with abundances of innate immunocytes (natural killer cells, macrophages etc.). HTRA3 plays a vital role in GC progression and prognosis and could be a moderate biomarker for prediction for survival after gastrectomy.

scholarly journals The association of sex-biased ATRX mutation in female gastric cancer patients with enhanced immunotherapy-related anticancer immunity

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
You Ge ◽  
Feiran Wei ◽  
Guoping Du ◽  
Gaoqiang Fei ◽  
Wei Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Enrichment Analysis ◽  
Genetic Alterations ◽  
Gene Set Enrichment Analysis ◽  
Gene Set Enrichment ◽  
Female Patients ◽  
Male Patients ◽  
Ifn Γ ◽  
Sex Biases ◽  
Anticancer Immunity

Abstract Background Genetic alterations have been proven to be the promising biomarkers for ICI response. However, sex biases in genetic alterations have been often ignored in the field of immunotherapy, which might specially influence the anticancer immunity and immunotherapy efficacy in male or female patients. Here, we have systematically evaluated the effect of the sex biases in somatic mutation of gastric cancer (GC) patients on the anticancer immunity and clinical benefit to immunotherapy. Methods Genomic and transcriptomic data of gastric cancer were downloaded from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC). We also obtained the genomic and clinical data of a MSKCC ICI-treated cohort from cbioportal database. GC male and female-derived tumor somatic mutation profiles were compared by maftools R package. Single sample gene set enrichment analysis (ssGSEA) was conducted to calculate the score of the anticancer immunity indicators including IFN-γ signaling, cytolytic activity (CYT) and antigen presenting machinery (APM). Results ATRX was found to mutate more frequently in female GC patients compared to male patients (FDR = 0.0108). Female GC patients with ATRX mutation manifested significantly more MSI-high subtypes, increased TMB and PDL1 expression as well as higher scores of IFN-γ signaling, CYT and APM. Gene set enrichment analysis (GSEA) has shown that ATRX mutation might enhance the immunogenicity and anticancer immunity through affecting DNA damage repair pathways. In the ICI-treated cohort from MSKCC, GC patients with ATRX mutation were associated with prolonged overall survival. When stratifying the entire ICI-treated cohort by sex, female patients with ATRX mutation obtained significantly better survival benefits than that of ATRX mutant male patients (Female patients, HR of ATRX MT vs WT = 0.636, 95%CI = 0.455–0.890, P = 0.023; Male patients, HR of ATRX MT vs WT = 0.929, 95%CI = 0.596–1.362, P = 0.712). Conclusions ATRX mutation might serve as a potential predictive biomarker for favorable clinical benefit to ICI in female GC patients. ATRX mutation could be applied in combination with other biomarkers of ICI response to better identify the female GC patients who will derive greater benefits from ICI therapy.

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