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

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.

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

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

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

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.

scholarly journals Identification of death-associated protein-like 1 (DAPL1) as a novel prognostic biomarker of breast cancer

2020 ◽  
Author(s):  
Haichao Zhang ◽  
Xin Qu ◽  
Lu Han
Keyword(s):  
Breast Cancer ◽  
Dna Repair ◽  
Survival Data ◽  
Immune Cell ◽  
Excision Repair ◽  
Analysis Data ◽  
Clinical Prognosis ◽  
Free Survival ◽  
Normal Tissues ◽  
M1 Macrophage

Abstract Background: It is meaningful to identify the potential clinical prognosis-associated oncogenes for cases with breast cancer, considering the complicated pathogenesis of breast cancer.Methods: We first utilized the bioinformatics approach to investigate the role of the DAPL1 (death-associated protein-like 1) in breast cancer, based on the available datasets of TCGA and GEO.Results: DAPL1 is lowly expressed in breast cancer tissues compared with the normal tissues. For the breast cancer cases of the TCGA-BRCA cohort, we observed a correlation between lowly expressed DAPL1 gene and poor clinical prognosis of overall survival ( P =0.0028). Based on the survival data of GEO, the low DAPL1 expression was associated with a poor prognosis of distant metastasis free survival ( P =0.0023), and relapse free survival ( P =0.0065). DAPL1 expression was linked to the mutation status or copy number variation o f several genes, such as MAP3K1 , NUP98 , and CCDC59. The infiltration level of immune cells (e.g., M1 macrophage, Follicular B helper T cells, etc.) may be involved in the etiology of breast cancer. Based on the DAPL1 -correlated genes, GSEA, GO, and KEGG analysis data indicated the association between DAPL1 expression and a series of biological issues, such as DNA packaging complex, DNA repair complex, nucleotide excision repair, ubiquitin-like protein binding, and ubiquitin proteasome pathway. We also identified several DAPL1 -associated phosphorylation kinases, such as MAPK, PRKACA, and GSK3B.Conclusions: DAPL1 gene is first identified as a prognosis biomarker of breast cancer, and the underlying molecular mechanism involves protein phosphorylation, immune cell infiltration, and DNA repair or protein ubiquitin-associated cellular pathways.

scholarly journals Identification of Flap Endonuclease 1 With Diagnostic and Prognostic Value in Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Min Wu ◽  
Pan Zhang ◽  
Penghui Wang ◽  
Zhen Fang ◽  
Yaqin Zhu
Keyword(s):  
Breast Cancer ◽  
Prognostic Marker ◽  
Prognostic Value ◽  
Diagnostic Value ◽  
Roc Curve Analysis ◽  
Free Survival ◽  
Flap Endonuclease 1 ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Kaplan Meier Plotter

ObjectiveThis study aims to identify the potential value of flap endonuclease 1 (FEN1) as a diagnostic and prognostic marker for breast cancer (BC).MethodsELISA was used to measure serum FEN1 levels and ECLIA for CA153 and CEA levels. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value. Oncomine and UALCAN databases were used to analyze the differences in FEN1 mRNA and protein expressions. Kaplan-Meier Plotter database was then used to assess the prognostic value.ResultsBioinformatics analysis showed that the FEN1 mRNA and protein levels were significantly higher in BC tissues than in normal tissues. FEN1 was detected in culture medium of BC cell lines and serum FEN1 concentrations were significantly increased in BC patients than in cancer-free individuals. Besides, FEN1 exhibited higher diagnostic accuracy (AUC values>0.800) than CA153 and CEA for distinguishing BC patients, especially early BC, from the healthy and benign groups, or individually. Additionally, serum FEN1 levels were significantly associated with the stage (P=0.001) and lymph invasion (P=0.016), and serum FEN1 levels were increased with the development of BC. Furthermore, serum FEN1 levels were significantly decreased in post-operative patients than in pre-operative patients (P=0.016). Based on the Kaplan-Meier Plotter database, the survival analysis indicated that FEN1 overexpression was associated with poor prognoses for overall survival (OS), relapse-free survival (RFS), and distant metastasis-free survival (DMFS) in BC patients.ConclusionFEN1 might be a novel diagnostic and prognostic marker for BC.

scholarly journals CDCA3 Is a Novel Prognostic Biomarker Associated with Immune Infiltration in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Zhihuai Wang ◽  
Shuai Chen ◽  
Gaochao Wang ◽  
Sun Li ◽  
Xihu Qin
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Immune Cell ◽  
Disease Free Survival ◽  
In Silico Analysis ◽  
Gene Markers ◽  
Free Survival ◽  
Immune Infiltration ◽  
Normal Tissues ◽  
Tumor Tissues

Cell division cycle-associated protein-3 (CDCA3) contributes to the regulation of the cell cycle. CDCA3 plays an important role in the carcinogenesis of various cancers; however, the association between CDCA3 expression, prognosis of patients, and immune infiltration in the tumor microenvironment is still unknown. Here, we demonstrated that CDCA3 was differentially expressed between the tumor tissues and corresponding normal tissues using in silico analysis in the ONCOMINE and Tumor Immune Estimation Resource (TIMER) databases. We analyzed the relationship between the expression of CDCA3 and prognosis of patients with hepatocellular carcinoma (HCC) using the Kaplan–Meier plotter database and Gene Expression Profiling Interactive Analysis (GEPIA). Furthermore, we determined the prognostic value of CDCA3 expression using univariate and multivariate analyses. We observed that CDCA3 expression closely correlated with immune infiltration and gene markers of infiltrating immune cells in the TIMER database. CDCA3 was highly expressed in the tumor tissues than in the adjacent normal tissues in various cancers, including HCC. Increased expression of CDCA3 was accompanied by poorer overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS). The correlation between CDCA3 expression and OS and disease-free survival (DFS) was also studied using GEPIA. CDCA3 expression was associated with the levels of immune cell infiltration and was positively correlated with tumor purity. Moreover, CDCA3 expression was associated with gene markers such as PD-1, CTLA4, LAG3, and TIM-3 from exhausted T cells, CD3D, CD3E, and CD2 from T cells, and TGFB1 and CCR8 located on the surface of Tregs. Thus, we demonstrated that CDCA3 may be a potential target and biomarker for the management and diagnosis of HCC.

scholarly journals Role of TSP-1 as prognostic marker in various cancers: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Shengjie Sun ◽  
Huiyu Dong ◽  
Tao Yan ◽  
Junchen Li ◽  
Chao Liang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Poor Prognosis ◽  
Meta Analysis ◽  
Gynecological Cancer ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Poor Overall Survival ◽  
Free Survival ◽  
The Impact

Abstract Background Published studies present conflicting data regarding the impact of Thrombospondin-1 (TSP-1) expression on prognosis of various cancers . We performed this meta-analysis to clarify the preliminary predictive value of TSP-1. Methods Twenty-four studies with a total of 2379 patients were included. A comprehensive literature search was performed by using PubMed, Cochrane Library, Web of Science, Embase, and hand searches were also conducted of relevant bibliographies. Pooled hazard ratio s ( HRs ) with 95% confidence intervals ( CIs ) for patient survival and disease recurrence were initially identified to explore relationships between TSP-1 expression and patient prognosis. Results A total of 24 eligible studies were included in this meta-analysis. Our results showed that high level of TSP-1 was correlated significantly with poor overall survival ( OS ) (HR=1.40, 95% CI: 1.17~1.68). However, high TSP-1 expression predicted no significant impact on progression-free survival ( PFS )/ metastasis-free survival (MFS ) (HR=1.35, 95%CI: 0.87-2.10) and disease-free survival ( DFS )/ recurrence-free survival ( RFS ) (HR = 1.40, 95%CI: 0.77–2.53). In addition, we performed subgroup analyses which showed that high TSP-1 expression predicted poor prognosis in breast cancer and gynecological cancer. Conclusions Our findings indicated high TSP-1 expression may serve as a promising biomarker of poor prognosis and novel therapeutic target in cancers, especially in breast cancer and gynecological cancer.

scholarly journals ceRNA Network Development and Tumour-infiltrating Immune Cell Analysis in Metastatic Breast Cancer of Bone

2020 ◽  
Author(s):  
Shuzhong Liu ◽  
An Song ◽  
Xi Zhou ◽  
Zhen Huo ◽  
Siyuan Yao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Bone Metastasis ◽  
Immune Cell ◽  
Rna Expression ◽  
Cell Analysis ◽  
Breast Cancer Patients ◽  
Cerna Network ◽  
Follicular Helper ◽  
Kaplan Meier

Abstract Background: Advanced breast cancer commonly metastasises to the bone and the molecular mechanism explaining the bone affinity of breast cancer cells is unclear. Thus, we developed nomograms based on a competing endogenous RNA (ceRNA) network and analysed tumour-infiltrating immunecells to elucidate the molecular pathways that may predict the prognosis of breast cancer patients.Methods: We obtained the RNA expression profile of 1091 primary breast cancer samples from The Cancer Genome Atlas database, 58 of which had bone metastasis. We analysed differential RNA expression patterns between breast cancer with and without bone metastasis and developed a ceRNA network. Cibersort was employed to differentiate between immune cell types based on tumour transcripts. Nomograms were then established using the ceRNA network and immune cell analysis. The value of prognostic factors was evaluated by Kaplan-Meier survival analysis and Cox proportional risk model.Results: There were significant differences in lncRNAs, 18 miRNAs, and 20mRNAs between breast cancer with and without bone metastasis, which were used to construct a ceRNA network. We found that the protein-coding genes gjb3, cammv, ptprz1,and fbn3 were significant in our Kaplan-Meier analysis. We also observed significant differences in plasma cell and follicular helper T cell populations between the two groups. In addition, the proportions of mast cells, gamma delta T cells, and plasma cells differed depending on disease location and stage. Our analysis revealed that a high proportion of follicular helper T cells and a low proportion of eosinophils promoted survival and that dlx6-as1, wnt6,and gabbr2expression may be related to bone metastasis of breast cancer.Conclusions: We provided a bioinformatic basis for exploring the molecular mechanism of bone metastasis in breast cancer patients and identified factors that may predict this.

scholarly journals Real-world effectiveness outcomes in patients diagnosed with metastatic triple-negative breast cancer

2020 ◽  
Author(s):  
Karen E Skinner ◽  
Amin Haiderali ◽  
Min Huang ◽  
Lee S Schwartzberg
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cox Regression ◽  
Unmet Need ◽  
Progression Free Survival ◽  
Free Survival ◽  
Regression Methods ◽  
Kaplan Meier ◽  
Community Oncology

Aim: This study examined treatment patterns and effectiveness outcomes of patients with metastatic triple-negative breast cancer (mTNBC) from US community oncology centers. Materials & methods: Eligible patients were females, aged ≥18 years, diagnosed with mTNBC between 1 January 2010 and 31 January 2016. Kaplan–Meier and Cox regression methods were used. Results: Sample comprised 608 patients with average age of 57.5 years and 505/608 patients (83.1%) received systemic treatment. Overall survival (OS) from first-line treatment found that African–American patients had shorter OS than White (9.3 vs 13.7 months; hazard ratio: 1.35; p = 0.006). Conclusion: More than 15% of women with mTNBC were not treated, indicating a high unmet need. Overall prognosis remains poor, which highlights the opportunity for newer therapies to improve progression-free survival and OS.

LTBP2 Serves as a Prognostic Biomarker and Correlated with the Immune Infiltration in Stomach and Colon Cancer

2021 ◽  
Author(s):  
Shuai Chen ◽  
Zhihuai Wang ◽  
Yu Gong ◽  
Hanyang Liu ◽  
Haojun Yang ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Transforming Growth Factor ◽  
Immune Cell ◽  
Disease Free Survival ◽  
Colon Adenocarcinoma ◽  
Progression Free Survival ◽  
Transforming Growth Factor Β ◽  
Gene Markers ◽  
Free Survival

Abstract Latent transforming growth factor β binding protein 2 (LTBP2) involved in the TGF pathway to induce immunosuppression and immune response. However, the association between the outcome of patients, the infiltrating immune cell and LTBP2 expression is still unclear in human cancers. The LTBP2 expression was analyzed by TIIMER and Oncomine database. Based on the Prognoscan database, the GEPIA database, and the Kaplan-Meier plotter database, the prognostic value was assessed. The immune and stromal score of tumors was calculated through ESTIMATE. We additionally explore the relationship among the LTBP2 expression, the infiltrating immune cells, and its gene markers in the TIMER, TISIDB, and GEPIA database, the enriched KEGG pathways of LTBP2 were evaluated by GSEA. The result showed that LTBP2 expressed differently among the normal and tumor tissues in various sorts of cancer involving stomach adenocarcinoma (STAD) and colon adenocarcinoma (COAD), and three cohorts of COAD presented that the LTBP2 high expression was linked with poorer disease-free survival and the elevated LTBP2 expression correlated with progression-free survival and poorer overall survival in STAD. The LTBP2 was correlated with the stromal and immune score in different cancers. The infiltrating immune cells include the CD8+T cells and CD4+T cells, macrophages, neutrophils, and dendritic cells were correlated with the LTBP2 expression. Meanwhile, LTBP2 was related to the infiltrating immune cell’s gene markers and enriched immune-related pathways in STAD and COAD. LTBP2 was the potential to be an independent predictor for the prognosis and a new target for immunotherapy in STAD and COAD.

scholarly journals Paclitaxel Promotes Tumor-Infiltrating Macrophages in Breast Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303382094582
Author(s):  
Jun Shen ◽  
Cong Chen ◽  
Zhaoqing Li ◽  
Shufang Hu
Keyword(s):  
Breast Cancer ◽  
Progression Free Survival ◽  
Cancer Prognosis ◽  
Migration And Invasion ◽  
P Value ◽  
Free Survival ◽  
Kaplan Meier ◽  
The Relationship ◽  
Kaplan Meier Plotter ◽  
Paclitaxel Treatment

Objective: Breast cancer remains the most threatening triggers of cancer death in women. Drug resistance inevitably leads to the weakness of treatment for breast cancer. Macrophages, as one of the most abundant immune cells in tumor immune-infiltrating microenvironment, involves in cell survival, migration, and invasion of breast cancer. Methods: In this study, we compared the proportions of macrophages in patients with breast cancer with and without paclitaxel treatment, and investigated the targeted genes associated with macrophages for paclitaxel response. To explore the relationship between drug-related genes and breast cancer prognosis, survival analysis based on the drug-related genes were performed by website of Kaplan-Meier plotter with the threshold of significant P value < .05. Results: Compared to the normal samples, we revealed that paclitaxel significantly enhanced the ratio of macrophages in the tumor microenvironment. Furthermore, the expression of 3 drug-related genes (IFT46, PEX11A, and TMEM223) were significantly negatively associated with the proportions of macrophages. And it is worth to notice that PEX11A and TMEM223 were associated with better progression-free survival outcomes of patients with breast cancer. Moreover, PEX11A was associated with longer overall survival time of breast cancer. Conclusion: Taken all together, all the findings support to gain a better understanding to the development of more effective therapies targeted with paclitaxel.

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