Heparanase is a novel biomarker for immune infiltration and prognosis in breast cancer.
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ABSTRACT:
SUBMITTER: Yang WJ
PROVIDER: S-EPMC8436937 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveHNRNPA2B1, one of the regulator of m6A methylation, is involved in a wide range of physiological processes. However, the aberrant expression of HNRNPA2B1 in Breast Cancer (BC) and its clinical significance still need to be further studied.MethodsWe used related databases to analyze the relationship between HNRNPA2B1 and BC by bioinformatics. Then, we further detected the expression of HNRNPA2B1 by immunohistochemical method, and analyzed the relationship between it and the prognosis of breast cancer by COX regression method.ResultsIn the study, we found that the expression level of HNRNPA2B1 in breast cancer (BC) was significantly higher than that in normal breast tissues. In addition, the expression level of HNRNPA2B1 in BC samples was significantly correlated with clinical indexes such as TNM stage. The Cox analysis revealed that the expression of HNRNPA2B1 in BC had significant clinical prognostic value. The results of immune infiltration of HNRNPA2B1 showed that there was a significant correlation between HNRNPA2B1 and immune cell subsets.ConclusionOur results show that the expression of HNRNPA2B1 in BC has important clinical diagnostic significance and high expression may be related with poor clinical outcome of BC. This helps to provide us with a new direction of BC targeted therapy.
| S-EPMC10522385 | biostudies-literature
Project description:BackgroundBreast invasive cancer (BRCA) is the most common malignancy and the second leading cause of malignancy death among women. Signal transducers and activators of transcription (STAT) family played a vital role in regulating certain biological processes and could serve as biomarkers for many diseases or cancers.MethodsThe expression, prognostic value, and clinical functions of STAT family in BRCA were evaluated with several bioinformatics web portals.ResultsThe expression of STAT5A/5B were downregulated in BRCA in subgroup analyses based on race, age, gender, race, subclasses, tumor histology, menopause status, nodal metastasis status, and TP53 mutation. BRCA patients with high STAT5B expression had a better overall survival, relapse free survival, MDFS and post progression survival. STAT5B expression level can impact the prognosis in BRCA patients with positive PR status, negative Her2 status and wild type TP53. Moreover, STAT5B was positively correlated with immune cell infiltration and the level of immune biomarkers. Drug sensitivity revealed that low STAT5B expression was resistant to the many small molecules or drugs. Functional enrichment analysis revealed that STAT5B was involved in adaptive immune response, translational initiation, JAK-STAT signaling pathway, Ribosome, NF-kappa B signaling pathway and Cell adhesion molecules.ConclusionsSTAT5B was a biomarker associated with prognosis and immune infiltration in breast cancer.
| S-EPMC9981440 | biostudies-literature
Project description:Breast cancer is the malignant tumor with the highest incidence rate at present, and its incidence rate ranks first in the female population. COL11A1 is an important component of collagen XI and is considered to play an important role in a variety of connective tissue diseases. Recent studies have shown that COL11A1 is associated with the occurrence and development of many kinds of malignant tumors. However, its prognostic value in breast cancer and its correlation with immune cell infiltration in tumor tissue are not clear. In this paper, we reveal the prognostic value of COL11A1 in breast cancer and its tumor immune-related function through in-depth bioinformatics analysis. The expression of COL11A1 is abnormally upregulated in breast cancer and is significantly related to the poor prognosis of breast cancer. In the analysis of the clinical characteristics of the patients, we found that the expression level of COLL11A1 was closely related to lymph node metastasis, PAM50 (Prediction Analysis of Microarray 50) expression, clinical stage and so on. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) all suggest that COL11A1 is related to tumor immunity. Further study found that the COL11A1 expression was significantly correlated with the degree of immune infiltration and the expression of a variety of immune cell markers in tumor tissue. More importantly, COL11A1 can affect the prognosis of breast cancer patients by participating in the regulation of tumor immune infiltration. Therefore, we believe that COL11A1 is a very potential target for diagnosis and treatment of breast cancer.
| S-EPMC9500398 | biostudies-literature
Project description:ObjectiveTriple negative breast cancer (TNBC) is a kind of cancer that endangers the lives of women all over the world in the 21st century. Heat shock protein member 8 (HSPA8) is the chaperone gene of the heat shock protein family. It is involved in many cellular functions. For example, it promotes the circulation between ATP and ADP, participates in protein folding, and can change the vitality of the cell and inhibit its growth. However, the abnormal expression of HSPA8 gene in TNBC and its diagnostic and prognostic significance still need to be further studied.MethodsFirst, we used related databases (such as TCGA, GEO, GTEx, ONCOMINE, TIMER2.0, UALCAN, HPA, STRING, CCLE, and Kaplan-Meier plotter databases) to analyze the relationship between HSPA8 and TNBC by bioinformatics. Then, the analysis using only a small part of the experimental work is used to explain our findings. For example, HSPA8 protein expression was evaluated by immunohistochemical method in TNBC tissues. Western blotting experiments were carried out to verify the results. Then, the clinicopathological characteristics of patients with TNBC were analyzed by R software and Cox regression analysis. On the basis, a nomogram is constructed to estimate the 1-, 3-, and 5-year overall survival (OS). The prognostic nomogram performance was calibrated and evaluated by the calibration curve and receiver operating characteristic (ROC) curve.ResultsIn the study, we analyzed the three GEO databases (including GSE86945, GSE106977, and GSE102088) and found that HSPA8 is one of the central genes of TNBC. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) researches indicated that HSPA8 was mainly involved in partner-mediated autophagy, mRNA catabolism, neutrophil activation, immune response, protein targeting, RNA splicing, RNA catabolism, and other biological processes. Next, we used bioinformatics technology to find that the expression level of HSPA8 in breast cancer (BC) and TNBC samples was significantly higher than that in normal breast tissues, which was determined by analyzing hospital patient samples and related experiments. In addition, the expression level of HSPA8 in BC and TNBC samples was significantly correlated with clinical indexes such as TNM stage. The Cox analysis revealed that the expression of HSPA8 in TNBC had significant clinical prognostic value. The results of nomogram and ROC test show that HSPA8 has significant predictive ability in TNBC. The results of immune infiltration of HSPA8 through the TIMER2.0 database showed that there was a significant correlation between HSPA8 and immune cell subsets.ConclusionsOur results show that the expression of HSPA8 in TNBC has important clinical diagnostic significance and clarify the potential molecular mechanism that promotes the evolution of TNBC. The high expression of HSPA8 may be related with the poor clinical outcome of TNBC. This helps to provide us with a new direction of TNBC targeted therapy.
| S-EPMC9705114 | biostudies-literature
Project description:Breast cancer is the most common malignancy in women, and there is evidence for the dual role of cell pyroptosis in tumor development. However, little is known about the relationship between cell pyroptosis and breast cancer and its prognostic value. We aimed to construct a prognostic model using cell-pyroptosis-related genes to provide innovative insights into the prognosis and treatment of breast cancer. We screened candidate genes for pyroptosis using public databases and identified 10 cell pyroptosis signature genes with the random forest method. Finally, a nomogram for predicting 1-, 3-, and 5-year survival probabilities was constructed. The differences in immune cell distributions between survival periods were similar across the breast cancer datasets. The 10 identified key pyroptosis factors showed a significant correlation with Her2, tumor-node-metastasis (TNM) stage, and survival of breast cancer. The risk scores correlated positively with the infiltration features of naive B cells, CD8+ T cells, atpdelnd mast cells, while they correlated negatively with those of M0 macrophages and dendritic cells. In conclusion, our findings confirm that cell pyroptosis is closely associated with breast cancer. Importantly, the prognostic complex values generated from the 10 cell-pyroptosis-related genes based on various clinical features may provide an important basis for future studies on the prognosis of breast cancer.
| S-EPMC9491236 | biostudies-literature
Project description:The chemokine CXCL9 (C-X-C motif chemokine ligand 9) has been reported to be required for antitumour immune responses following immune checkpoint blockade. In this study, we sought to investigate the potential value of CXCL9 according to immune responses in patients with breast cancer (BC). A variety of open-source databases and online tools were used to explore the expression features and prognostic significance of CXCL9 in BC and its correlation with immune-related biomarkers followed by subsequent verification with immunohistochemistry experiments. The CXCL9 mRNA level was found to be significantly higher in BC than in normal tissue and was associated with better survival outcomes in patients with ER-negative tumours. Moreover, CXCL9 is significantly correlated with immune cell infiltration and immune-related biomarkers, including CTLA4, GZMB, LAG3, PDCD1 and HAVCR2. Finally, we performed immunohistochemistry with breast cancer tissue samples and observed that CXCL9 is highly expressed in the ER-negative subgroup and positively correlated with the immune-related factors LAG3, PD1, PDL1 and CTLA4 to varying degrees. These findings suggest that CXCL9 is an underlying biomarker for predicting the status of immune infiltration in ER-negative breast cancer.
| S-EPMC8435794 | biostudies-literature
Project description:BackgroundNew immunotherapeutic strategies based on predictors are urgently needed. Toll-like receptor adaptor interacting with SLC15A4 on the lysosome (TASL) was recently confirmed to fulfill an important role in the innate immune response. However, whether TASL is involved in tumor development and immunotherapy response prediction has not been reported.MethodsTCGA and GTEx were used to yield transcriptional, genetic, and epigenetic levels of TASL in 33 cancer types. CIBERSORT was used to explore the correlation between TASL expression and multiple immune-related signatures and tumor-infiltrating immune cell content in different cancer types. The ability of TASL to predict tumor immunotherapy response was analyzed in seven datasets. Finally, we tested TASL expression in human glioma cell lines and tissue samples and analyzed its correlation with clinicopathological parameters.ResultsTASL is widely heterogeneous at the transcriptional, genetic, and epigenetic levels. High TASL expression is an independent poor prognostic factor for immune "cold" tumor Low-Grade Glioma (LGG) but an opposite factor for "hot" tumors Lung Adenocarcinoma (LUAD) and Skin Cutaneous Melanoma (SKCM). TASL may affect tumor immune infiltration by mediating tumor-infiltrating lymphocytes and tumor-associated macrophages. It may differentially affect the prognosis of the three cancers by regulating the immunosuppressive microenvironment in LGG and the immunostimulatory microenvironment in LUAD and SKCM. High TASL expression is a potential biomarker for the positive response to immunotherapy in cancers such as SKCM and was also experimentally confirmed to be positively associated with adverse clinicopathological features of gliomas.ConclusionTASL expression is an independent prognostic factor for LGG, LUAD, and SKCM. High TASL expression is a potential biomarker for the positive response to immunotherapy in certain cancer types such as SKCM. Further basic studies focusing on TASL expression and tumor immunotherapy are urgently needed.
| S-EPMC10251564 | biostudies-literature
Project description:BackgroundCurrent studies on the role of ARHGAP39 mainly focused on its effect on neurodevelopment. However, there are few studies on the comprehensive analysis of ARHGAP39 in breast cancer.MethodsARHGAP39 expression level was analyzed based on the Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression Project (GTEx), and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database and validated by qPCR in various cell lines and tumor tissues. The prognostic value was analyzed using Kaplan-Meier curve analysis. CCK-8 and transwell assays were conducted to identify the biological function of ARHGAP39 in tumorigenesis. Signaling pathways related to ARHGAP39 expression were identified by the GO and KEGG enrichment analysis and gene set enrichment analysis (GSEA). The correlations between ARHGAP39 and cancer immune infiltrates were investigated via TIMER, CIBERSORT, ESTIMATE and tumor-immune system interactions database (TISIDB).ResultsARHGAP39 was overexpressed in breast cancer and associated with poor survival outcomes. In vitro experiments revealed that ARHGAP39 could facilitate the proliferation, migration, and invasion capability of breast cancer cells. GSEA analysis showed that the main enrichment pathways of ARHGAP39 was immunity-related pathways. Considering the immune infiltration level, ARHGAP39 was negatively associated with infiltrating levels of CD8 + T cell and macrophage, and positively associated with CD4 + T cell. Furthermore, ARHGAP39 was significantly negatively correlated with immune score, stromal score, and ESTIMATE score.ConclusionsOur findings suggested that ARHGAP39 can be used as a potential therapeutic target and prognostic biomarker in breast cancer. ARHGAP39 was indeed a determinant factor of immune infiltration.
| S-EPMC10184379 | biostudies-literature
Project description:Breast cancer (BRCA) is a common malignancy worldwide that is associated with a high mortality rate. Despite recent improvements in diagnosis and treatment, there is an urgent need to investigate the processes underlying cancer progression and identify novel prognostic indicators. Anoikis, which plays a role in the development of human malignant tumors, has been gaining increasing interest from researchers. However, the potential role of anoikis-related genes (ANRGs) in the advancement of BRCA remains unknown. In this study, we aimed to assess the predictive value of ANRGs in BRCA, construct a prognostic model based on ANRGs, and explore the tumor microenvironment in different prognostic score groups. This study utilized data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to collect clinical information and RNA sequencing data from patients with BRCA. Information on ANRGs was gathered from GeneCards and Harmonizome portals. A risk score model based on ANRGs was created using least absolute shrinkage and selection operator Cox (LASSO) regression analysis. Additionally, the study explored the tumor microenvironment and enriched pathways in different risk groups. Finally, a novel ANRG-based nomogram is developed. A total of 142 differentially expressed genes associated with survival were identified, of which 5 genes were selected to create the ANRG signature. The risk score based on this signature proved to be an independent prognostic factor. Further analysis revealed that different risk subgroups exhibited variations in the tumor microenvironment and drug sensitivities. Subsequently, a nomogram was developed using risk scores and clinicopathological factors. The decision curve analysis results suggest that patients with BRCA might derive clinical treatment benefits from utilizing this prognostic model. Based on the results of this study, the ANRG signature and nomograph established can be used for clinical decision-making in patients with BRCA.
| S-EPMC10615559 | biostudies-literature
Project description:Ferroptosis, a newly discovered way of cell death, has been proved to be involved in the oncogenesis and development of cancers, including colorectal cancer (CRC). Here, by identifying the differentially expressed genes (DEGs) from three CRC transcriptome microarray datasets (GSE20842, GSE23878, and GSE25070), we found that the expression of MT1G was significantly decreased in CRC tissues, and the patients with a high level of MT1G displayed a poor prognosis. Quantitative PCR (qPCR) further confirmed the downregulated MT1G in two CRC cells, HCT8 and HCT116. The colony-forming assay indicated that the MT1G overexpression exhibited a remarkable inhibition of cell proliferation in HCT8 and HCT116 cells. In addition, we explored the co-expressed genes of MT1G to gain a better understanding of its potential signaling pathways. Aberrantly expressed MT1G also affected the immune response of CRC patients. Collectively, these findings might deepen our comprehension on the potential biological implications of MT1G in CRC.
| S-EPMC9065264 | biostudies-literature