Identification CXCL9 is a Potential Prognostic Biomarker in Ovarian and Gastric Cancer and is Correlated with Immune Infiltrates

Abstract Background CXCL9 also known as an interferon gamma-inducible chemokine that belonging to the CXC chemokine family. It plays a role in promoting chemotaxis, inducing leukocyte differentiation and multiplication, and triggering tissue extravasation. Methods The TIMER (Tumor Immune Estimation Resource) and cancer microarray database Oncomine were used to dig at CXCL9 expression. The clinic prognostic level of CXCL9 was evaluated via Kaplan-Meier plotter. Then, Using TIMER and GEPIA, we investigated whether CXCL9 expression impacted cancer immune infiltrates. Results CXCL9 expression has been found to be significantly lower in ovarian and gastric cancers relative to normal tissues. In patients with ovarian cancer (OS HR = 0.78, P = 0.0017; PFS HR = 0.85, R = 0.015) and gastric cancer (OS HR = 0.55, P = 1.1e-08; PFS HR = 0.58, R = 7.6e-07), low CXCL9 expression was correlation to PFS (progression-free survival) and OS (poor overall survival). Furthermore, in OV and GC, CXCL9 was shown to have a close interaction with tumor-infiltrating immunity cells (B cells, CD4 + and CD8 + T cells, macrophages, neutrophils, and dendritic cells). CXCL9 expression, on the other hand, was shown to be closely related to several immune markers. Conclusion In OV and GC, CXCL9 mRNA level is strongly associated with prognosis and levels of penetration tumor-infiltrating immunity cell. The CXCL9 expression may also play a role in controlling TAMs (tumor-associated macrophages), DCs (Dendritic cells), CTLs (cytotoxic lymphocytes), and NK (natural killer) cells in OV and GC. CXCL9 may be seen as an independent marker that assesses the prognosis in OV and GC patients. Besides, CXCL9 expression level also can assess the immune cell subtypes of tumor microenvironment in OV and GC.

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Identification CXCL9 is a Potential Prognostic Biomarker in Ovarian and Gastric Cancer and is Correlated with Immune Infiltrates

10.21203/rs.3.rs-350037/v2 ◽

2021 ◽

Author(s):

Shuwei Li ◽

Ruijun Shi ◽

Hangzheng Zhou ◽

Dongyang Wang ◽

Kunlong Zhu ◽

...

Keyword(s):

Gastric Cancer ◽

Dendritic Cells ◽

Immune Cell ◽

Mrna Level ◽

Progression Free Survival ◽

Cytotoxic Lymphocytes ◽

Poor Overall Survival ◽

Normal Tissues ◽

Microarray Database ◽

Kaplan Meier

Abstract Background: CXCL9 also known as an interferon gamma-inducible chemokine that belonging to the CXC chemokine family. It plays a role in promoting chemotaxis, inducing leukocyte differentiation and multiplication, and triggering tissue extravasation. Methods: The TIMER (Tumor Immune Estimation Resource) and cancer microarray database Oncomine were used to dig at CXCL9 expression. The clinic prognostic level of CXCL9 was evaluated via Kaplan-Meier plotter. Then, Using TIMER and GEPIA, we investigated whether CXCL9 expression impacted cancer immune infiltrates. Results: CXCL9 expression has been found to be significantly lower in ovarian and gastric cancers relative to normal tissues. In patients with ovarian cancer (OS HR = 0.78, P = 0.0017; PFS HR = 0.85, R = 0.015) and gastric cancer (OS HR = 0.55, P = 1.1e-08; PFS HR = 0.58, R = 7.6e-07), low CXCL9 expression was correlation to PFS (progression-free survival) and OS (poor overall survival). Furthermore, in OV and GC, CXCL9 was shown to have a close interaction with tumor-infiltrating immunity cells (B cells, CD4+ and CD8+ T cells, macrophages, neutrophils, and dendritic cells). CXCL9 expression, on the other hand, was shown to be closely related to several immune markers.Conclusion: In OV and GC, CXCL9 mRNA level is strongly associated with prognosis and levels of penetration tumor-infiltrating immunity cell. The CXCL9 expression may also play a role in controlling TAMs (tumor-associated macrophages), DCs (Dendritic cells), CTLs (cytotoxic lymphocytes), and NK (natural killer) cells in OV and GC. CXCL9 may be seen as an independent marker that assesses the prognosis in OV and GC patients. Besides, CXCL9 expression level also can assess the immune cell subtypes of tumor microenvironment in OV and GC.

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PECAM-1 is a prognostic-related biomarker and correlated with immune infiltrates in breast cancer

10.21203/rs.3.rs-451009/v1 ◽

2021 ◽

Author(s):

Qingfang Yue ◽

Fei Wang ◽

Fei Cao ◽

Xianglong Duan ◽

Jun Bai

Keyword(s):

Breast Cancer ◽

T Cells ◽

Invasive Carcinoma ◽

Immune Cell ◽

Progression Free Survival ◽

Immune Gene ◽

Poor Overall Survival ◽

Free Survival ◽

Normal Tissues ◽

Kaplan Meier

Abstract Background: Breast invasive carcinoma (BRCA) is the primary cause of cancer-associated mortality worldwide. Platelet endothelial cell adhesion molecule 1 (PECAM-1) has been implicated in a number of important biological processes. However, the interrelation between PECAM-1 gene expression, tumor immunity, and prognosis of patients with BRCA is unclear. The current study is aimed to analyze the expression and clinical significance of PECAM-1 in breast cancer and the correlation between PECAM-1 and immune infiltrations. Methods: The differential expressions of PECAM-1 in breast cancer tissues and normal tissues were evaluated via exploring TIMER, Oncomine and UALCAN databases; the relationship within expression level of PECAM-1 and outcome of breast patients was evaluated via Kaplan-Meier plotter and PrognoScan; the methylation of PECAM-1 were investigated through the MethSurv platform; the correlation between PECAM-1 and tumor immune cell infiltration was further investigated by TIMER and GEPIA databases; the correlation between PECAM-1 and gene makers of immune infiltration were checked using TIMER and GEPIA. Results: There were significant differences in PECAM-1 expression levels between breast invasive carcinoma tissues and adjacent normal tissues. Low PECAM-1 expression was significantly related to poor overall survival, progression-free survival and distant metastasis free survival in patients with breast cancer. In DNA methylation level, PECAM-1 hypermethylation in three CpG sites (cg20830094, cg00427260 and cg00879592) showed poor survival in breast cancer. PECAM-1 expression exhibited significantly positive correlations with the levels of infiltrated B cell, CD4+T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells in breast cancer. Furthermore, PECAM-1 expression is positively correlated with multiple immune gene makers in breast cancer.Conclusion: The expression of PECAM-1 can serves as a prognostic biomarker in breast invasive carcinoma and is correlated with immune infiltrates.

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RAI14 Is a Prognostic Biomarker and Correlated With Immune Cell Infiltrates in Gastric Cancer

Technology in Cancer Research & Treatment ◽

10.1177/1533033820970684 ◽

2020 ◽

Vol 19 ◽

pp. 153303382097068

Author(s):

Yu Xiao ◽

Hongpan Zhang ◽

Guobo Du ◽

Xue Meng ◽

Tingting Wu ◽

...

Keyword(s):

Gastric Cancer ◽

Immune Cells ◽

Immune Cell ◽

Progression Free Survival ◽

Clinicopathological Parameters ◽

Marker Genes ◽

Poor Overall Survival ◽

Kaplan Meier ◽

The Impact ◽

Kaplan Meier Plotter

Objective: To analyze the expression and clinical significance of retinoic acid-induced protein 14 ( RAI14) in gastric cancer and its relationship with immune cell infiltration by mining databases such as Oncomine, TIMER, UALCAN, and Kaplan Meier Plotter. Methods: RAI14 expression in various cancer types was analyzed using the Oncomine and TIMER databases. We used the Kaplan-Meier Plotter and UALCAN databases to evaluate the impact of RAI14 on clinicopathological parameters in gastric cancer. The correlation between RAI14 expression and immune cell invasion was studied using TIMER. TIMER was also used to analyze the correlation between RAI14 expression and marker levels of tumor-infiltrating immune cells. Results: High RAI14 expression in gastric cancer was significantly associated with poor overall survival (OS; hazard ratio [HR] = 1.82, 95% confidence interval [CI] = 1.53–2.15, P < 0.001) and poor progression-free survival (PFS; HR = 2.16, 95% CI = 1.77–2.65, P < 0.001). Furthermore, high RAI14 expression was significantly associated with poor prognosis of patients with stage 2–4 gastric cancer, but not with OS and PFS of stage 1 patients (OS P = 0.17; PFS P = 0.09), and patients with stage N0 PFS had nothing to do (PFS P = 0.238). RAI14 expression was positively correlated with the infiltration levels of monocytes, tumor-associated macrophages, macrophages, neutrophils, and Treg cells in gastric cancer. Besides, RAI14 expression was closely related to various marker genes in immune cells. Conclusion: RAI14 is highly expressed in gastric cancer, and its expression level is correlated with the prognosis of patients with gastric cancer. RAI14 plays also an important role in the recruitment and regulation of infiltrating immune cells and is, thus, expected to become a target for the optimal treatment of gastric cancer.

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KLHL5 Is a Prognostic-Related Biomarker and Correlated With Immune Infiltrates in Gastric Cancer

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2020.599110 ◽

2020 ◽

Vol 7 ◽

Author(s):

Qiulin Wu ◽

Guobing Yin ◽

Jinwei Lei ◽

Jiao Tian ◽

Ailin Lan ◽

...

Keyword(s):

Gastric Cancer ◽

Clinical Outcomes ◽

Immune Cell ◽

Progression Free Survival ◽

Differentially Expressed ◽

Free Survival ◽

Kaplan Meier ◽

Patient Prognosis ◽

The Relationship ◽

Kaplan Meier Plotter

Background: KLHL5 (Kelch Like Family Member 5) is differentially expressed in gastric cancer, but its correlation with prognosis and functioning mechanism in gastric cancer remain unclear.Methods: The Oncomine database and TIMER were employed to appraise the KLHL5 expression in a variety of cancers. The correlation between KLHL5 expression and patient prognosis was extracted from the Kaplan–Meier plotter, GEPIA, and PrognoScan database. Then the relationship between KLHL5 expression and inflammatory infiltrate profiles was inquired by TIMER. Finally, GEPIA and TIMER were explored for the correlative significance between KLHL5 expression and immune cell–related marker sets.Results: KLHL5 was found to be differentially expressed and correlated with clinical outcomes in several types of cancers in the TCGA database. Especially, KLHL5 mRNA expression was upregulated and correlated with poorer overall survival and progression-free survival in gastric cancer. Moreover, elevated KLHL5 expression was significantly related with patient node stage, infiltration level, and expression of multiple immune marker sets.Conclusions: These results implicate that KLHL5 expression is closely linked with patient clinical outcomes and the microenvironmental infiltration level in different neoplasms. This indicates that KLHL5 is a modulator in infiltrate recruitment, shaping the landscape of immune cell infiltration. Thus, it represents an eligible prognostic predictor for gastric malignancy.

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Oncological Effects and Prognostic Value of AMAP1 in Gastric Cancer

Frontiers in Genetics ◽

10.3389/fgene.2021.675100 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jiao Li ◽

Shan Tian ◽

Yingyun Guo ◽

Weiguo Dong

Keyword(s):

Gastric Cancer ◽

Prognostic Value ◽

Meta Analysis ◽

Progression Free Survival ◽

Bioinformatic Analysis ◽

Luciferase Assay ◽

Migration And Invasion ◽

Diagnostic Significance ◽

Poor Overall Survival ◽

Normal Tissues

PurposeWe examined the diagnostic significance, prognostic value, and potential function of AMAP1 in gastric cancer (GC).MethodsComprehensive bioinformatic analysis was conducted to investigate differential expression of AMAP1 mRNA and protein in GC. Meta-analyses were utilized to determine the overall prognostic correlation of AMAP1 mRNA in patients with GC. A panel of vitro assays was applied to assess target microRNA and AMAP1 protein in GC cell lines and tissues, respectively.ResultsAMAP1 mRNA and protein levels were upregulated in GC specimens, compared to matched normal tissues. AMAP1 mRNA exhibited promising results regarding differential diagnosis of GC and normal tissue. Meta-analysis based on the TCGA and GEO databases revealed that high AMAP1 mRNA abundance was associated with poor overall survival (HR = 1.42; 95% CI: 1.06–1.89) and was correlated with reduced progression-free survival (HR = 1.89; 95% CI: 1.51–2.36) in GC patients. Moreover, AMAP1 was negatively correlated with miR-192-3p (r = −0.3843; P < 0.0001). A dual-luciferase assay revealed that miR-192-3p targeted AMAP1. Levels of miR-192-3p were significantly higher in GC tissues and GC cells than in normal tissues and cells. Moreover, AMAP1 silencing resulted in reduced GC proliferation, migration, and invasion.ConclusionAMAP1 is a novel oncogene in GC and is negatively correlated with by miR-192-3p. AMAP1 may act as a diagnostic and prognostic marker of GC.

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Identification of key genes related to macrophage infiltration in gastric cancer based on WGCNA

10.21203/rs.3.rs-56342/v1 ◽

2020 ◽

Author(s):

Haiyan Chen ◽

Cangang Zhang ◽

Shuai Cao ◽

Meng Cao ◽

Nana Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Immune Cell ◽

Accurate Diagnosis ◽

Marker Genes ◽

Hub Genes ◽

Normal Tissues ◽

Tumor Tissues ◽

New Strategy ◽

Tumor Environment ◽

Advanced Stages

Abstract Background: Gastric cancer (GC) is rampant around the world. Most of the GC cases are detected in advanced stages with poor prognosis. The identification of marker genes for early diagnosis is of great significance. Studying the tumor environment is helpful to acknowledge the process of tumorigenesis, development, and metastasis.Methods: In GEO, 22 kinds of immune cell infiltration were calculated by CIBERSORT. Macrophages were discovered remarkably infiltrated higher in GC compared with normal tissues. WGCNA was utilized to construct the network and then identify key modules and genes related to macrophages in TCGA.Results: Finally, 18 hub genes were verified. In the PPI bar chart, the top 3 genes were chosen as hub genes involved in most pathways. On the TIMER and THPA websites, it is verified that the expression levels of CYBB, CD86 and C3AR1 genes in tumor tissues were higher than those in normal tissues.Conclusion: These genes may work as biomarkers or targets for accurate diagnosis and treatment of GC in the future. Our findings may be a new strategy for the treatment of GC.

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Immune Cell Landscape in Gastric Cancer

BioMed Research International ◽

10.1155/2021/1930706 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Yang Yang ◽

Wei He ◽

Zi-rui Wang ◽

Yu-jiao Wang ◽

Lan-lan Li ◽

...

Keyword(s):

Gastric Cancer ◽

B Cells ◽

Immune Cells ◽

Immune Cell ◽

Univariate Analysis ◽

Molecular Therapy ◽

Expression Level ◽

Regulatory Factors ◽

Normal Tissues ◽

The Relationship

Background. The tumor-infiltrating immune cells are closely associated with the prognosis of gastric cancer (GC). This article is aimed at determining the composition change of immune cells and immune regulatory factors in GC and normal tissues, depicting their prognosis value in GC, and revealing the relationship between them and GC clinical parameters. Methods. We used CIBERSORT to calculate the proportion of 22 immune cells in the GC or normal tissues; a t -test was applied to assess the expression difference of immune cells and immune regulatory factors in normal and GC tissues. The relationship of the immune cells, immune regulatory factors, and GC patients’ clinical characteristics was assessed by univariate analysis. Results. In this study, we found that the proportion of macrophages increased, while plasma cells and monocytes decreased in GC tissues. In these immune fractions, Tregs and naïve B cells were found to be correlated with GC patients’ prognosis. Interestingly, the expression of immune regulatory factors was ambiguous with their classical function in GC tissues. For example, TIM-3, FOXP3, and CMTM6 were overexpressed, while CD27 and PD-1 were underexpressed in GC tissues. We also found that IDO1, PD-1, TIGIT, and TIM-3 were highly expressed in high-grade GC tissues, the HERC2 expression level was related to patients’ gender, and the TIGIT expression level was sensitive to targeted therapy. Furthermore, our results suggested that the infiltration of Tregs and naive B cells was strongly correlated with the T stage, radiation therapy, targeted molecular therapy, and the expression levels of TIM-3 and FOXP3 in GC. Conclusion. The expression pattern of tumor-infiltrating immune cells and immune regulatory factors was systematically depicted in the GC tumor microenvironment, indicating that individualized treatment based on the tumor-infiltrating immune cells and immune regulatory factors may be beneficial to GC patients.

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GJA1 Expression and Its Prognostic Value in Cervical Cancer

BioMed Research International ◽

10.1155/2020/8827920 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Silu Meng ◽

Xinran Fan ◽

Jianwei Zhang ◽

Ran An ◽

Shuang Li

Keyword(s):

Gene Expression ◽

Cervical Cancer ◽

Logistic Regression ◽

Gap Junction ◽

Signaling Pathway ◽

Immune Cells ◽

Immune Cell ◽

Normal Tissues ◽

Kaplan Meier ◽

Chi Squared

Gap Junction Protein Alpha 1 (GJA1) belongs to the gap junction family and has been widely studied in cancers. We evaluated the role of GJA1 in cervical cancer (CC) using public data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. The difference of GJA1 expression level between CC and normal tissues was analyzed by the Gene Expression Profiling Interactive Analysis (GEPIA), six GEO datasets, and the Human Protein Atlas (HPA). The relationship between clinicopathological features and GJA1 expression was analyzed by the chi-squared test and the logistic regression. Kaplan–Meier survival analysis and Cox proportional hazard regression analysis were used to assessing the effect of GJA1 expression on survival. Gene set enrichment analysis (GSEA) was used to screen the signaling pathways regulated by GJA1. Immune Cell Abundance Identifier (ImmuCellAI) was chosen to analyze the immune cells affected by GJA1. The expression of GJA1 in CC was significantly lower than that in normal tissues based on the GEPIA, GEO datasets, and HPA. Both the chi-squared test and the logistic regression showed that high-GJA1 expression was significantly correlated with keratinization, hormone use, tumor size, and FIGO stage. The Kaplan–Meier curves suggested that high-GJA1 expression could indicate poor prognosis ( p = 0.0058 ). Multivariate analysis showed that high-GJA1 expression was an independent predictor of poor overall survival (HR, 4.084; 95% CI, 1.354-12.320; p = 0.013 ). GSEA showed many cancer-related pathways, such as the p53 signaling pathway and the Wnt signaling pathway, were enriched in the high-GJA1-expression group. Immune cell abundance analysis revealed that the abundance of CD8 naive, DC, and neutrophil was significantly increased in the high-GJA1-expression group. In conclusion, GJA1 can be regarded as a potential prognostic marker of poor survival and therapeutic target in CC. Moreover, many cancer-related pathways may be the critical pathways regulated by GJA1. Furthermore, GJA1 can affect the abundance of immune cells.

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Association between intratumoral HER2 heterogeneity (IHH) and trastuzumab (T-mab) efficacy in HER2 positive–gastric cancer (GC).

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.92 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 92-92

Author(s):

Takeru Wakatsuki ◽

Noriko Yamamoto ◽

Keisho Chin ◽

Mariko Ogura ◽

Eiji Shinozaki ◽

...

Keyword(s):

Gastric Cancer ◽

Statistical Tests ◽

Progression Free Survival ◽

Clinical Impact ◽

Heterogeneous Group ◽

Rank Test ◽

Her2 Positive ◽

Kaplan Meier ◽

Significant Difference ◽

The Difference

92 Background: ToGA study showed superiority of adding T-mab to standard chemotherapy and a positive correlation between HER2 expression levels and the T-mab efficacy. In gastric cancer IHH is frequently recognized but its clinical impact on T-mab efficacy is unclear. Methods: Patients who were treated with T-mab and had surgical specimens available for IHC test were retrospectively examined. When all tumor cells overexpressed HER2 protein by IHC, the tumor was defined as non-HER2-heterogeneous. The others were defined as HER2-heterogeneous. Progression-free survival (PFS) and overall survival (OS) were estimated using by Kaplan-Meier methods and compared by the log-rank test. The level of significance was set to p<0.05 and all statistical tests were two-sided. Results: 23 patients were enrolled. Their median age was 68 years and 83% were male. PS 0, GEJ cancer, intestinal type histology, visceral metastasis (lung or liver), and previous chemotherapy were found in 57%, 35%, 83%, 57%, and 57% of them, respectively. After a median follow-up of 11.3 months, the median OS, PFS, and overall response rate were 14.4 months, 10.8 months, and 62.5%, respectively. All tumors were IHC3+, and 13 were non-HER2-heterogeneous and 10 were HER2-heterogeneous. There was no significant difference in clinicopathological features between the two groups. Median PFS in non-HER2-heterogeneous group (21.9 months) was significantly longer than that in HER2-heterogeneous group (8.6 months), (HR: 0.24 [0.06-0.91], P=0.024). Median OS in non-HER2-heterogeneous group was not reached while that in HER2-heterogeneous group was 12.9 months (HR: 0.29 [0.06-1.42], P=0.102). A higher rate of response to T-mab was seen in non-HER2-heterogeneous group than in HER2-heterogeneous group, though the difference was not statistically significant (75% vs. 50%, p=0.608). Conclusions: IHH might have robust clinical impact on T-mab efficacy for HER2 positive GC. These findings should be validated by independent large cohorts and further molecular correlative analyses are warranted.

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Prognosis and immune function of Synaptotagmin-4 in gastric cancer and brain low-grade glioma

10.21203/rs.3.rs-21652/v1 ◽

2020 ◽

Author(s):

Siyuan Jiang ◽

Lizhe Zhu ◽

Chao Jiang ◽

Shibo Yu ◽

Bin Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Immune Function ◽

Treg Cells ◽

Low Grade Glioma ◽

Low Grade ◽

Lower Grade ◽

Expression Levels ◽

Immune Infiltration ◽

Normal Tissues ◽

Kaplan Meier

Abstract Background Synaptotagmins (SYTs) are a family of proteins whose primary feature is the calcium sensor in vesicle transport and exocytosis. SYT4 is one of them, but the relationship between SYT4 and cancer remains unclear. We aim to explore the prognosis and immune function of SYT4 in gastric cancer and low-grade glioma. Methods These databases were used to study the immunological and prognostic role of SYT4 in cancers, including the Oncomine database, Kaplan-Meier plotter, GEPIA2, TIMER, and CGGA. Results The study suggested that the expression levels of SYT4 were lower in both gastric cancer and glioma, compared to the normal tissues. And SYT4 played a protective and harmful role in low-grade gliomas and gastric cancer, respectively. Moreover, we found that a difference between SYT4 expression and the levels of immune infiltration in stomach adenocarcinoma (STAD) and brain lower-grade glioma (LGG). Besides, after exploring the association between the expression levels of SYT4 and markers of immune cells in these two cancers, we found that markers of monocytes, M1/ M2, tumor-associated macrophages (TAMs), Treg cells and SYT4 expressions had an opposite correlation in STAD and LGG. Conclusions SYT4 had an effect on the prognosis of gastric cancer and glioma patients and was related to immune infiltration by regulating TAMs and Treg cells. SYT4 can be used as a prognostic biomarker for STAD and LGG.

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