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

2020 ◽  
Vol 19 ◽  
pp. 153303382097068
Author(s):  
Yu Xiao ◽  
Hongpan Zhang ◽  
Guobo Du ◽  
Xue Meng ◽  
Tingting Wu ◽  
...  

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.

2021 ◽  
Author(s):  
Tinghui Wu ◽  
Yongchao Li ◽  
Shujuan Gong ◽  
Ruijun Shi ◽  
Hangzheng Zhou ◽  
...  

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.


2021 ◽  
Author(s):  
Shuwei Li ◽  
Ruijun Shi ◽  
Hangzheng Zhou ◽  
Dongyang Wang ◽  
Kunlong Zhu ◽  
...  

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.


2020 ◽  
Vol 7 ◽  
Author(s):  
Qiulin Wu ◽  
Guobing Yin ◽  
Jinwei Lei ◽  
Jiao Tian ◽  
Ailin Lan ◽  
...  

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.


2021 ◽  
Author(s):  
Jiaxi Feng ◽  
Yanan Hu ◽  
Dan Liu ◽  
Shanshan Wang ◽  
Mengci Zhang ◽  
...  

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.


2021 ◽  
Vol 41 (9) ◽  
Author(s):  
Chen Qiu ◽  
Zuyin Li ◽  
Wanyue Cao ◽  
Xiaoni Cai ◽  
Li Ye ◽  
...  

Abstract Purpose: Liver hepatocellular carcinoma (LIHC) is one of the most common primary malignant liver tumors worldwide. The RAD52 motif-containing protein 1 (RDM1) has been shown to play a role in mediating DNA damage repair and homologous recombination. The present study was designed to determine the expression of RDM1 and its prognostic value as well as its relationship with immune infiltration in LIHC patients. Methods: Oncomine and Tumor Immunoassay Resource were used to assess the expression of RDM1. PrognoScan and Kaplan–Meier bioinformatics database were used to analyze the impact of clinical influencing factors on prognosis. Finally, the Tumor Immune Assessment Resource (TIMER) and Gene Expression Analysis Interactive Analysis (GEPIA) databases were used to detect the correlation between the expression of RDM1 and expression of marker genes related to immune infiltration. Immunohistochemistry (IHC) method was used to detect the expression level of RDM1 in 90 cases of hepatocellular carcinoma and adjacent normal liver tissues. Results: RDM1 expression was up-regulated in most cancers. The expression of RDM1 was remarkably higher than that of the corresponding normal control genes in LIHC tissues. The increase in RDM1 messenger RNA (mRNA) expression was closely related to the decreases in overall survival (OS) and progression-free survival (PFS). Additionally, the increase in RDM1 mRNA expression was closely related to the infiltration levels of macrophages, CD8+ T cells and B cells and was positively correlated with a variety of immune markers in LIHC. Conclusion: The findings of the present study demonstrate that RDM1 is a potentially valuable prognostic biomarker that can help determine the progression of cancer and is associated with immune cell infiltration in LIHC.


2021 ◽  
Author(s):  
Jiaxi Feng ◽  
Yanan Hu ◽  
Dan Liu ◽  
Shanshan Wang ◽  
Mengci Zhang ◽  
...  

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.


2021 ◽  
Vol 11 ◽  
Author(s):  
Cailin Xue ◽  
Peng Gao ◽  
Xiaohan Cui ◽  
Xudong Zhang ◽  
Jin Lei ◽  
...  

BackgroundThe enzyme L-asparaginase (ASRGL1) catalyzes the hydrolysis of L-asparagine (Asn) to L-aspartic acid (Asp) and ammonia. Numerous studies have shown a strong correlation between ASRGL1 expression and tumorigenesis. However, the expression and biological function of ASRGL1 in hepatocellular carcinoma (HCC) are still unclear.MethodsWe explored the mRNA expression of ASRGL1 in HCC using the HCCDB, Oncomine, and TIMER 2.0 databases. Western blotting and immunohistochemical analyses were also used to determine the mRNA expression of ASRGL1 in HCC. LinkedOmics was used to analyze the genes co-expressed with ASRGL1 and regulators including kinases, miRNAs, and transcription factors. The Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the co-expressed genes were also investigated using LinkedOmics. The correlation between ASRGL1 expression and immune infiltrates was analyzed using the TIMER 2.0 and Gene Expression Profiling Interactive Analysis (GEPIA) databases. The effects of ASRGL1 expression on patient outcome were investigated using the UALCAN and GEPIA databases, and the Kaplan–Meier plotter. c-Bioportal was used to explore the mutations of ASRGL1 in HCC.ResultsCompared with the adjacent tissues, ASRGL1 was upregulated in HCC. High ASRGL1 expression in HCC indicated poor relapse-free survival, progression-free survival, disease-specific survival, and overall survival. The expression of ASRGL1 was significantly correlated with infiltrating levels of B cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in HCC.ConclusionOur findings suggest that ASRGL1 is overexpressed in HCC and that ASRGL1 expression was significantly correlated with immune infiltration in HCC and prognosis. Therefore, ASRGL1 may serve as a biomarker for the early diagnosis and treatment of HCC.


2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A986-A986
Author(s):  
Tao Shi ◽  
Yipeng Zhang ◽  
Yue Wang ◽  
Yunfeng Pan ◽  
Hanbing Wang ◽  
...  

BackgroundGastric cancer (GC) is a highly heterogeneous and immunosuppressive cancer type with poor prognosis. Current immunotherapies like immune checkpoint blockade (ICB) have very modest therapeutic effect in GC patients, reflecting urgent need for exploring new immunotherapeutic targets.MethodsIHC and mRNA analysis of 384 patients from Drum Tower Hospital Cohort and 1192 patients from other databases were performed to investigate Dickkopf-1 (DKK1) expression and local immune status. The MFC-challenged subcutaneous and abdominal dissemination GC models were established, and the impact of DKK1 blockade on gastric tumor immune microenvironment (TIME) and anti-tumor responses was explored by flow cytometry and RNA sequencing. In vivo immune cell-depletion GC models were constructed to further assess the function of DKK1 on different immune cell types. RAW264.7 and mouse bone marrow derived macrophages (BMDMs) were employed to analyze DKK1 modulation on macrophages in vitro by Cytometric Bead Array, flow cytometry and western bolt.ResultsIn present study, we found high DKK1 expression is associated with poor overall survival and worse immune status in GC patients. DKK1 blockade could improve gastric TIME, including increased accumulation and activation of CD8+ T cells and NK cells, and trigger an effective anti-tumor response both in subcutaneous and abdominal dissemination GC models. DKK1 directly induces macrophages towards an immunosuppressive phenotype, while the TIME improvement and tumor reduction depend on the reversion of immunosuppressive macrophages mediated by DKK1 blockade. Furthermore, combined inhibition of PD-1 and DKK1 could achieve superior anti-tumor effect on GC models.ConclusionsThus, our work identifies a new role of DKK1 to induce immunosuppressive TIME through macrophage modulation, and reveals DKK1 to be a novel and promising immunotherapeutic target for GC.Ethics ApprovalThe collection and analysis of tumor tissue sections were approved by the Ethics Committee of Nanjing University Medical School Affiliated Drum Tower Hospital (2021-324-01). All animal experiments were approved by the Institutional Animal Care and Use Committee of Drum Tower Hospital (approval number: 2020AE01064).


2021 ◽  
Author(s):  
Qingfang Yue ◽  
Fei Wang ◽  
Fei Cao ◽  
Xianglong Duan ◽  
Jun Bai

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.


Author(s):  
Kuang-Tsu Yang ◽  
Chia-Jung Li ◽  
Renin Chang ◽  
Jui-Tzu Wang ◽  
Yih-Wen Tarng ◽  
...  

Background: Gastric cancer (GC) is one of the leading malignancy diseases worldwide, especially in Asian. CAST is a potential oncogene in GC carcinogenesis process. The character of macrophage infiltration in GC microenvironment was also unaddressed. Methods: We first applied machine searching in gene candidate evaluation of GC. CAST expression was analyzed via the Human Protein Atlas (HPA) and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database. Protein-protein interaction (PPI) network was downloaded from STRING. We investigated the impact of CAST on clinical prognosis using Kaplan-Meier plotter. The correlations between CAST and Lgr5 and macrophage infiltration in GC was surveyed via TIMER 2.0. Finally, GeneMANIA was also used to evaluate the possible functional linkage between genes. Results: After machine-assisted searching, CAST expression was found signicant difference in the overall survival of GC patients. STRING revealed CAST related proteomics and transcriptomics associations, mainly about CAPN family. Moreover, CAST significantly impacts the prognosis of GC from other datasets validation. Notably, high CAST expression was correlated with worse overall survival in GC patients (hazard ratio = 1.59; logrank P = 9.4 x 10-8). CAST and Lgr5 expressions were both positively correlated with WNT 2 and WNT 2B. Among GC patients in several datasets, CAST and macrophage infiltration evaluated together showed no obvious trend toward poor clinical overall survival. Conclusion: CAST plays an important role in GC clinical prognosis and is associated with WNT 2/WNT 2B/Lgr5. Our study denmostrated that CAST in GC overall survival is regulated by macrophage infiltration.


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