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1.
This study investigated the expression of zinc finger E-box binding homeobox 2 (ZEB2), its prognostic significance in various cancers, and the correlation between ZEB2 and infiltrating immune cells and ZEB2-related proteins in ovarian cancer (OV). The Gene Expression Profiling Interactive Analysis tool was used to analyze RNA sequencing data and cancer survival rates, based on normal and tumor tissue data available in The Cancer Genome Atlas (TCGA) database. The Kaplan–Meier plotter and PrognoScan databases were used to analyze the prognostic value of ZEB2 in OV (n = 1144). The Tumor Immune Estimation Resource was used to investigate the correlation between ZEB2 and infiltrating immune cells in various cancers, including OV. High ZEB2 expression was associated with a poorer prognosis in OV. In OV, ZEB2 is positively correlated with CD8+T cells, neutrophils, macrophages, and dendritic cell invasion; and ZEB2 is negatively correlated with tumor-infiltrating B cells. The STRING database was used to investigate the correlations with ZEB2-related proteins. The results reveal that ZEB2 was positively correlated with SMAD1 and SMAD2 in OV. Our findings may serve as a potential prognostic biomarker, and provide novel insights into the tumor immunology in OV. Thus, ZEB2 may be a potential diagnostic and therapeutic target in OV.  相似文献   

2.
CUGBP Elav-like family member 2(CELF2) plays crucial roles in the development and activation of T cell. However, the impacts of CELF2 on tumour-infiltrating immune cells (TIICs) and clinical outcomes of tumours remain unclear. In this study, we found that elevated CELF2 expression was markedly correlated with prolonged survival in multiple tumours, particularly in breast and lung cancers. Notably, CELF2 only impacted the prognosis of triple-negative breast cancer (TNBC) with lymph node metastasis. Further investigation showed CELF2 expression was positively correlated with the infiltration abundance of dendritic cells (DCs), CD8+ T cells and neutrophils in breast invasive carcinoma (BRCA) and DCs in lung squamous cell carcinoma (LUSC). CELF2 also had strong correlations with markers of diverse TIICs such as T cells, tumour-associated macrophages and DCs in BRCA and LUSC. Importantly, CELF2 was significantly associated with plenty of immune checkpoint molecules (ICMs) and outperformed five prevalent biomarkers including PD-1, PD-L1, CTLA-4, CD8 and tumour mutation burden in predicting immunotherapeutic responses. Immunohistochemistry also revealed lower protein levels of CELF2 in TNBC and LUSC compared to normal tissues, and patients with high expression showed significantly prolonged prognosis. In conclusion, we demonstrated that increased CELF2 expression was closely related to better prognosis and superior TIIC infiltration and ICM expression, particularly in BRCA and LUSC. CELF2 also performed well in evaluating the immunotherapeutic efficacy, suggesting CELF2 might be a promising biomarker.  相似文献   

3.
Gynaecologic and breast cancers share some similarities at the molecular level. The aims of our study are to highlight the similarities and differences about IDO1, an important immune‐related gene in female cancers. The NGS data from TCGA of cervical squamous cell carcinoma (CESC), ovarian serous cystadenocarcinoma (OV), uterine corpus endometrial carcinoma (UCEC), uterine carcinosarcoma (UCS) and breast invasive carcinoma (BRCA) were analysed to identify molecular features, and clinically significant and potential therapeutic targets of IDO1. We found IDO1 was significantly up‐regulated in four gynaecologic cancers and breast cancer. According to breast cancer PAM50 classification scheme, IDO1 expression was higher in tumours of basal than other subtypes and showed better survival prognosis in BRCA and OV. Through immune infiltration analysis, we found a strong correlation between IDO1 and immune cell populations especially for dendritic cells and T cells. In addition, we investigated the association between IDO1 and tumour mutation burden (TMB) and found that IDO1 was significantly correlated with TMB in BRCA and CESC. GSVA revealed that hallmarks significantly correlated with IDO1 were involved in interferon gamma response, allograft rejection and inflammatory response. We also found PD‐L1 and LAG3 were highly positive related to IDO1 in gynaecologic cancers when comparing with their corresponding normal tissues. Our results indicated that IDO1 participated in anti‐tumour immune process and is correlated with mutation burden. These findings may expand our outlook of potential anti‐IDO1 treatments.  相似文献   

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Ovarian cancer (OC) is the most lethal gynaecological cancer with genomic complexity and extensive heterogeneity. This study aimed to characterize the molecular features of OC based on the gene expression profile of 2752 previously characterized metabolism-relevant genes and provide new strategies to improve the clinical status of patients with OC. Finally, three molecular subtypes (C1, C2 and C3) were identified. The C2 subtype displayed the worst prognosis, upregulated immune-cell infiltration status and expression level of immune checkpoint genes, lower burden of copy number gains and losses and suboptimal response to targeted drug bevacizumab. The C1 subtype showed downregulated immune-cell infiltration status and expression level of immune checkpoint genes, the lowest incidence of BRCA mutation and optimal response to targeted drug bevacizumab. The C3 subtype had an intermediate immune status, the highest incidence of BRCA mutation and a secondary optimal response to bevacizumab. Gene signatures of C1 and C2 subtypes with an opposite expression level were mainly enriched in proteolysis and immune-related biological process. The C3 subtype was mainly enriched in the T cell-related biological process. The prognostic and immune status of subtypes were validated in the Gene Expression Omnibus (GEO) dataset, which was predicted with a 45-gene classifier. These findings might improve the understanding of the diversity and therapeutic strategies for OC.  相似文献   

6.
PurposeHead and neck squamous cell carcinoma (HNSCC) is a highly invasive malignancy with poor survival. Perforin (PRF1) plays essential roles in host immunity. Our research intended to identify the correlations of PRF1 with clinical prognosis and tumor immune infiltration in HNSCC.MethodsWe explored PRF1 expression and its associations with the clinical features of HNSCC via the Tumor Immune Estimation Resource (TIMER), Oncomine and The Cancer Genome Atlas (TCGA) databases. The prognostic value of PRF1 for HNSCC was further explored by Kaplan–Meier plotter and TIMER. Finally, the relation between PRF1 and immune infiltration in HNSCC was estimated via CIBERSORT and TIMER.ResultsPRF1 expression was remarkably elevated in HNSCC and associated with clinical stage and HPV infection. High PRF1 expression predicted favorable outcomes in HNSCC, especially in HPV+ HNSCC. Moreover, higher infiltration of CD8+ T cells and CD4+ T cells were found in the PRF1high group of HNSCC. PRF1 expression in HNSCC was strongly correlated with infiltrating CD8+ T cells and dendritic cells (DCs), with higher relevance in HPV+ HNSCC.ConclusionOur findings suggested that PRF1 could be a novel prognostic biomarker in HNSCC and that its expression was related to immune cell infiltration, which was impacted by HPV status.Key words: PRF1, prognosis, head and neck squamous cell carcinoma, tumor immune infiltration, HPV  相似文献   

7.
TGFβ2 is an essential regulator of immune cell functionality, but the mechanisms whereby it drives immune infiltration in gastric cancer remain uncertain. The Oncomine and Tumor Immunoassay Resource (TIMER) databases were used for assessing the expression of TGFβ2, after which TIMER was used to explore the relationship between TGFβ2 and tumour immune infiltration. Finally, we assessed how TGFβ2 expression correlated with the expression of a set of marker genes associated with immune infiltration using TIMER and GEPIA. We determined TGFβ2 expression to be significantly correlated with outcome in multiple types of cancer in the Cancer Genome Atlas (TCGA), with the effect being particularly pronounced in gastric cancer. Furthermore, elevated TGFβ2 expression was found to be significantly correlated with gastric cancer N staging, and with the expression of a variety of immune markers associated with particular immune cell subsets. These results indicate that TGFΒ2 is associated with patient outcome and tumour immune cell infiltration in multiple cancer types. This suggests that TGFβ2 is a key factor which governs immune cell recruitment to gastric cancer tumours, potentially playing a vital role in governing immune cell infiltration and thus representing a valuable prognostic biomarker in gastric cancer patients.  相似文献   

8.
通过生物信息学研究细胞色素b561(Cytochromes b561,CYB561)与浸润性乳腺癌(Breast invasive carcinoma,BRCA)不良预后的相关性.CYB561氨基酸序列高度保守,在人体组织中广泛表达,可能预示着广泛的细胞功能.CYB561在多种癌症中的失调,提示其可能参与人类癌症发生发...  相似文献   

9.
Background: The family with sequence similarity 20-member C (Fam20C) kinase plays important roles in physiopathological process and is responsible for majority of the secreted phosphoproteome, including substrates associated with tumor cell migration. However, it remains unclear whether Fam20C plays a role in cancers. Here, we aimed to analyze the expression and prognostic value of Fam20C in pan-cancer and to gain insights into the association between Fam20C and immune infiltration.Methods: We analyzed Fam20C expression patterns and the associations between Fam20C expression levels and prognosis in pan-cancer via the ONCOMINE, TIMER (Tumor Immune Estimation Resource), PrognoScan, GEPIA (Gene Expression Profiling Interactive Analysis), and Kaplan–Meier Plotter databases. After that, GEPIA and TIMER databases were applied to investigate the relations between Fam20C expression and immune infiltration across different cancer types, especially BLCA (bladder urothelial carcinoma), LGG (brain lower grade glioma), and STAD (stomach adenocarcinoma).Results: Compared with adjacent normal tissues, Fam20C was widely expressed across many cancers. In general, Fam20C showed a detrimental role in pan-cancer, it was positively associated with poor survival of BLCA, LGG, and STAD patients. Specifically, based on TCGA (The Cancer Genome Atlas) database, a high expression level of Fam20C was associated with worse prognostic value in stages T2–T4 and stages N0–N2 in the cohort of STAD patients. Moreover, Fam20C expression had positive associations with immune infiltration, including CD4+ T cells, macrophages, neutrophils, and dendritic cells, and other diverse immune cells in BLCA, LGG, and STAD.Conclusion: Fam20C may serve as a promising prognostic biomarker in pan-cancer and has positive associations with immune infiltrates.  相似文献   

10.
The discovery of early diagnosis and prognostic markers for breast cancer can significantly improve survival and reduce mortality. LSM1 is known to be involved in the general process of mRNA degradation in complexes containing LSm subunits, but the molecular and biological functions in breast cancer remain unclear. Here, the expression of LSM1 mRNA in breast cancer was estimated using The Cancer Genome Atlas (TCGA), Oncomine, TIMER and bc‐GenExMiner databases. We found that functional LSM1 inactivation caused by mutations and profound deletions predicted poor prognosis in breast cancer (BRCA) patients. LSM1 was highly expressed in both BRCA tissues and cells compared to normal breast tissues/cells. High LSM1 expression is associated with poorer overall survival and disease‐free survival. The association between LSM1 and immune infiltration of breast cancer was assessed by TIMER and CIBERSORT algorithms. LSM1 showed a strong correlation with various immune marker sets. Most importantly, pharmacogenetic analysis of BRCA cell lines revealed that LSM1 inactivation was associated with increased sensitivity to refametinib and trametinib. However, both drugs could mimic the effects of LSM1 inhibition and their drug sensitivity was associated with MEK molecules. Therefore, we investigated the clinical application of LSM1 to provide a basis for sensitive diagnosis, prognosis and targeted treatment of breast cancer.  相似文献   

11.
Autophagy maintains cellular homeostasis by degrading and recycling cytoplasmic components under stress conditions, which is identified to be involved in tumorigenesis and now has been recognized as novel target in cancer treatment. In present study, we gathered total autophagy-related genes and established an autophagy-related genes signature (ATGRS) through LASSO cox regression analysis in BLCA. Kaplan-Meier survival and multivariate cox regression analyses both showed the ATGRS was a robust independent prognostic factor with high accuracy. Subsequently, integrated analyses indicated that ATGRS had a strong correlation with molecular subtypes, clinicopathological characteristics and somatic mutation alteration. Moreover, ATGRS was found to be positively correlated with the infiltration of immune cells in tumour microenvironment (TME) and immune checkpoint expression, indicating the potent role of autophagy by regulating the TME. In addition, ATGRS was proved to be efficient in predicting the clinical benefit of immune checkpoint inhibitors (ICIs) based immunotherapy and chemotherapy in BLCA. Furthermore, we observed abnormal expression levels of autophagy-related genes and found the different behaviour of ATGRS in pancancer by LASSO cox regression analysis. Therefore, construction of ATGRS in BLCA could help us to interpret the underlying mechanism of autophagy and sheds a light on the clinical application for a combination of autophagy modification with targeted immunotherapy and chemotherapy in BLCA.  相似文献   

12.
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.  相似文献   

13.
Tumour microenvironment (TME) is crucial to tumorigenesis. This study aimed to uncover the differences in immune phenotypes of TME in endometrial cancer (EC) using Uterine Corpus Endometrial Carcinoma (UCEC) cohort and explore the prognostic significance. We employed GVSA enrichment analysis to cluster The Cancer Genome Atlas (TCGA) EC samples into immune signature cluster modelling, evaluated immune cell profiling in UCEC cohort (n = 538) and defined four immune subtypes of EC. Next, we analysed the correlation between immune subtypes and clinical data including patient prognosis. Furthermore, we analysed the expression of immunomodulators and DNA methylation modification. The profiles of immune infiltration in TCGA UCEC cohort showed significant difference among four immune subtypes of EC. Among each immune subtype, natural killer T cells (NKT), dendritic cells (DCs) and CD8+T cells were significantly associated with EC patients survival. Each immune subtype exhibited specific molecular classification, immune cell characterization and immunomodulators expression. Moreover, the expression immunomodulators were significantly related to DNA methylation level. In conclusion, the identification of immune subtypes in EC tissues could reveal unique immune microenvironments in EC and predict the prognosis of EC patients.  相似文献   

14.
The immune system and the tumor interact closely during tumor development. Aberrantly expressed long non-coding RNAs (lncRNAs) may be potentially applied as diagnostic and prognostic markers for gastric cancer (GC). At present, the diagnosis and treatment of GC patients remain a formidable clinical challenge. The present study aimed to build a risk scoring system to improve the prognosis of GC patients. In the present study, ssGSEA was used to evaluate the infiltration of immune cells in GC tumor tissue samples, and the samples were split into a high immune cell infiltration group and a low immune cell infiltration group. About 1262 differentially expressed lncRNAs between the high immune cell infiltration group and the low immune cell infiltration group. About 3204 differentially expressed lncRNAs between GC tumor tissues and paracancerous tissues were identified. Then, 621 immune-related lncRNAs were screened using a Venn analysis based on the above results, and 85 prognostic lncRNAs were identified using a univariate Cox analysis. We constructed a prognostic signature using LASSO analysis and evaluated the predictive performance of the signature using ROC analysis. GO and KEGG enrichment analyses were performed on the lncRNAs using the R package, ‘clusterProfiler’. The TIMER online database was used to analyze correlations between the risk score and the abundances of the six types of immune cells. In conclusion, our study found that specific immune-related lncRNAs were clinically significant. These lncRNAs were used to construct a reliable prognostic signature and analyzed immune infiltrates, which may assist clinicians in developing individualized treatment strategies for GC patients.  相似文献   

15.
The tumor microenvironment is highly correlated with tumor occurrence, progress, and prognosis. We aimed to investigate the immune-related gene (IRG) expression and immune infiltration pattern in the tumor microenvironment of lower-grade glioma (LGG). We employed the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm to calculate immune and stromal scores and identify prognostic IRG based on The Cancer Genome Atlas data set. The potential molecular functions of these genes were explored with the help of functional enrichment analysis and the protein–protein interaction network. Remarkably, three cohorts that were downloaded from the Chinese Glioma Genome Atlas database were analyzed to further verify the prognostic values of these genes. Moreover, the Tumor IMmune Estimation Resource (TIMER) algorithm was used to estimate the abundance of infiltrating immune cells and explore the immune infiltration pattern in LGG. And unsupervised cluster analysis determined three clusters of the immune infiltration pattern and indicated that CD8+ T cells and macrophages were significantly associated with LGG outcomes. Altogether, our study identified a list of prognostic IRGs and provided a perspective to explore the immune infiltration pattern in LGG.  相似文献   

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17.
Breast carcinoma (BRCA) is the most common carcinoma among women worldwide. Despite the great progress achieved in early detection and treatment, morbidity and mortality rates remain high. In the present study, we make a systematic analysis of BRCA using TCGA database by applying CIBERSORT and ESTIMATE computational methods, uncovered CD3D as a prognostic biomarker by intersection analysis of univariate COX and protein–protein interaction (PPI). It revealed that high CD3D expression was strongly associated with poor survival of BRCA, based on The Cancer Genome Atlas (TCGA) database and online websites. Gene Set Enrichment Analysis (GSEA) revealed that the high CD3D expression group was mainly enriched for the immune-related pathways and the low CD3D expression group was mainly enriched for metabolic-related activities. Based on CIBERSORT analysis, the difference test and correlation test suggested that CD3D had a strong correlation with T cells, particularly CD8 + T cells, which indicated that CD3D up-regulation may increase T cell immune infiltration in the TME and induce antitumor immunity by activating T lymphocytes. Furthermore, the correlation analysis showed that CD3D expression had a strongly positive correlation with immune checkpoints, which indicating that the underlying mechanism involves CD3D mediated regulation of T cell functions in BRCA, and single cell RNA-seq analysis revealed that CD3D correlate with CD8 + T cells and it is itself highly expressed in CD8 + T cells. In summary, we identified a prognostic biomarker CD3D in BRCA, which was associated with lymphocyte infiltration, immune checkpoints and could be developed for innovative therapeutics of BRCA.  相似文献   

18.
Ovarian cancer (OC) is associated with high mortality rate. However, the correlation between immune microenvironment and prognosis of OC remains unclear. This study aimed to explore prognostic significance of OC tumour microenvironment. The OC data set was selected from the cancer genome atlas (TCGA), and 307 samples were collected. Hierarchical clustering was performed according to the expression of 756 genes. The immune and matrix scores of all immune subtypes were determined, and Kruskal-Wallis test was used to analyse the differences in the immune and matrix scores between OC samples with different immune subtypes. The model for predicting prognosis was constructed based on the expression of immune-related genes. TIDE platform was applied to predict the effect of immunotherapy on patients with OC of different immune subtypes. The 307 OC samples were classified into three immune subtypes A-C. Patients in subtype B had poorer prognosis and lower survival rate. The infiltration of helper T cells and macrophages in microenvironment indicated significant differences between immune subtypes. Enrichment analyses of immune cell molecular pathways showed that JAK–STAT3 pathway changed significantly in subtype B. Furthermore, predictive response to immunotherapy in subtype B was significantly higher than that in subtype A and C. Immune subtyping can be used as an independent predictor of the prognosis of OC patients, which may be related to the infiltration patterns of immune cells in tumour microenvironment. In addition, patients in immune subtype B have superior response to immunotherapy, suggesting that patients in subtype B are suitable for immunotherapy.  相似文献   

19.
大量证据表明microRNA(miRNA)通过靶向调控靶基因的表达从而在肿瘤侵袭与转移中发挥重要作用。然而关于microRNA-216b-5p (miR-216b-5p )通过靶向嗜乳脂蛋白第3亚家族膜蛋白A2(butyrophilin subfamily 3 member A2,BTN3A2)促进胶质瘤侵袭与转移的机制尚不明确。本研究通过GSE15824与GSE4290差异表达分析筛选出同时在2个芯片中表达上调的BTN3A2(P<0.05)。生存曲线结果显示,高表达BTN3A2病人总生存期明显下降(P<0.001)。表达量分析结果显示,BTN3A2表达随WHO分级升高而升高(P<0.05),同时1p/19q未联合缺失与IDH突变型病人BTN3A2表达升高(P<0.001)。基因集富集分析(gene set enrichment analysis,GSEA)结果显示,BTN3A2与众多癌症相关通路有关(P<0.05);Western印迹结果显示,BTN3A2在7例胶质瘤组织和胶质瘤细胞系U87、U251和LN-229中表达上调,过表达miR-216b-5p (miR-216b-5p mimics)后BTN3A2蛋白表达水平降低;Transwell结果显示,转染BTN3A2干扰质粒(si-BTN3A2)和miR-216b-5p mimics后可以抑制LN 229细胞体外迁移与侵袭能力(P<0.05);在线预测网站证实,miR-216b-5p 为BTN3A2潜在靶基因;生存曲线结果显示,与低表达miR-216b-5p 病人相比,高表达病人生存率明显上调(P=0.025);荧光定量RT PCR结果显示,miR-216b-5p 在胶质瘤U87、U251和LN-229细胞中表达下降(P<0.05);双荧光素酶结果显示,BTN3A2存在与miR-216b-5p 的结合靶点(P<005);综上所述,BTN3A2可能通过结合miR-216b-5p 促进胶质瘤细胞LN 229的迁移以及侵袭。  相似文献   

20.
Background: Recurrent locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC) is associated with dismal prognosis because of its highly invasive behavior and resistance to conventional intensive chemotherapy. The identification of effective markers for early diagnosis and prognosis is important for reducing mortality and ensuring that therapy for HNSCC is effective. Proteasome 26S subunit, non-ATPase 7 (PSMD7) is an ATP-independent component of the 19S regulatory subunit. The prognostic value of PSMD7 and the association with immune infiltration in HNSCC remains unclear.Methods: The Sangerbox, Oncomine, UALCAN and Human Protein Atlas (HPA) databases were used to examine PSMD7 expression profiles in HNSCC. The CVCDAP was used to analysis the association of PSMD7 with the prognosis of patients with HNSCC. The mechanism was investigated with gene set enrichment analysis (GSEA). The association between expression of PSMD7 and immune infiltration in HNSCC was investigated using the Tumor Immune Estimation Resource (TIMER), TISIDB database and CIBERSORT algorithm.Results: PSMD7 expression was significantly up-regulated in HNSCC compared with relative normal tissues. In addition, up-regulated PSMD7 expression was associated with various clinicopathological parameters. High expression of PSMD7 suggested inferior survival of HNSCC patients. GSEA and CERES score indicated that PSMD7 was closely correlated with tumor-related signaling pathways and cell survival. Functional analyses revealed that PSMD7 was positively correlated with various infiltration levels. Moreover, PSMD7 influenced the prognosis of HNSCC patients partially via immune infiltration.Conclusion: Our findings suggest that PSMD7 is associated poor prognosis in patients with HNSCC and plays an important role in tumor-related immune infiltration.  相似文献   

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