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The aim of this study was to reveal genes associated with breast cancer metastasis, to investigate their intrinsic relationship with immune cell infiltration in the tumor microenvironment, and to screen for prognostic biomarkers. Gene expression data of breast cancer patients and their metastases were downloaded from the GEO, TCGA database. R language package was used to screen for differentially expressed genes, enrichment analysis of genes, PPI network construction, and also to elucidate key genes for diagnostic and prognostic survival. Spearman’s r correlation was used to analyze the correlation between key genes and infiltrating immune cells. We screened 25 hub genes, FN1, CLEC5A, ATP8B4, TLR7, LY86, PTGER3 and other genes were differentially expressed in cancer and paraneoplastic tissues. However, patients with higher expression of CD1C, IL-18 breast cancer had a better prognosis in the 10 years survival period, while patients with high expression of FN1, EIF4EBP1 tumors had a worse prognosis. In addition, TP53 and HIF1 genes are closely related to the signaling pathway of breast cancer metastasis. In this study, gene expression of ATP8B4 and CD1C were correlated with cancer tissue infiltration of CD8+ T lymphocytes, while GSE43816, GSE62327 and TCGA databases showed that CD8+ T lymphocytes were closely associated with breast cancer progression. Functional enrichment analysis of genes based on expression differences yielded key genes of prognostic value in the breast cancer microenvironment.  相似文献   

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Gastric cancer (GC) is one of the most common cancer worldwide. Although emerging evidence indicates thatautophagy-related long non-coding RNA (lncRNA) plays an important role in the progression of GC, the prognosis ofGC based on autophagy is still deficient. The Cancer Genome of Atlas stomach adenocarcinoma (TCGA-STAD) datasetwas downloaded and separated into a training set and a testing set randomly. Then, 24 autophagy-related lncRNAs werefound strongly associated with the survival of the TCGA-STAD dataset. 11 lncRNAs were selected to build the risk scoremodel through the least absolute shrinkage and selection operator (LASSO) regression. Every patient got a risk score (RS),and patients were separated into a high-risk group and a low-risk group due to the median RS. The multivariate Coxanalysis showed that the RS could be an independent prognosis predictor. The Kaplan-Meier survival analysis and theReceiver Operating Characteristic (ROC) curve indicated the model had an excellent prediction effect. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the mRNAs in the prognosticnetwork were mainly involved in the autophagy and ubiquitin-like protein ligase binding. Gene Set EnrichmentAnalysis (GSEA) analysis uncovered that the differentially expressed genes (DEGs) in the high-risk group partiallyparticipated in the ECM receptor interaction and other signaling pathways. Our results indicated that the risk scoremodel based on the autophagy-related lncRNAs performed well in the prediction of prognosis for patients with GC.  相似文献   

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Pentraxin-3 (PTX3), the prototype of long pentraxins, seems to influence complement system (CS) modulation.PTX3 and CS sustain carcinogenesis, enriching tumor microenvironment (TME) with pro-inflammatory moleculespromoting angiogenesis in prostate cancer (PC) and renal cell carcinoma (RCC). Furthermore, cancer cellsoverexpress complement regulatory proteins, such as CD46, CD55 and CD59, which negatively affect complementpathways for support cancer cells survival. This viewpoint aims to elucidate the ambivalent role of PTX3 and the CSin the context of tumor microenvironment (TME).  相似文献   

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Esophageal cancer (EC) was an aggressive malignant neoplasm characterized by high morbidity and poor prognosis. Identifying the changes in DNA damage repair genes helps to better understand the mechanisms of carcinoma progression. In this study, by comparing EC samples and normal samples, we found a total of 132 DDR expression with a significant difference. Moreover, we revealed higher expression of POLN, PALB2, ATM, PER1, TOP3B and lower expression of HMGB1, UBE2B were correlated to longer OS in EC. In addition, a prognostic risk score based on 7 DDR gene expression (POLN, HMGB1, TOP3B, PER1, UBE2B, ATM, PALB2) was constructed for the prognosis of EC. Meanwhile, EC cancer samples were divided into 3 subtypes based on 132 DDR genes expressions. Clinical profile analysis showed cluster C1 and C2 showed a similar frequency of T2, which was remarked higher than that in cluster 3. Moreover, we found the immune cell inflation levels were significantly changed in different subtypes of EC. The infiltration levels of T cell CD8+, B cell and NK cells were greatly higher in cluster 2 than that in cluster 1 and cluster 3. The results showed T cell CD4+ infiltration levels were dramatically higher in cluster 1 than that in cluster 2 and cluster 3. Finally, we perform bioinformatics analysis of DEGs among 3 subtypes of EC and found DDR genes may be related to multiple signaling, such as Base excision repair, Cell cycle, Hedgehog signaling pathway, and Glycolysis/Gluconeogenesis. These results showed DDR genes may serve as new target for the prognosis of EC and prediction of the potential response of immune therapy in EC.  相似文献   

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Background: Ovarian cancer (OC) is a leading cause of gynecological cancer-linked deaths worldwide. Exosomal miR-1825 and its target gene C-type lectin domain family 5 member A (CLEC5A) are associated with tumorigenesis in cancers that was further probed. Methods: Exosomal miR-1825 expression in exosomes and its impact on overall survival (OS) prediction were determined using Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data. Target genes of miR-1825 were searched in five prediction databases and prognostically significant differentially expressed genes were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were carried out. The ability of CLEC5A to predict OS was evaluated using univariate and multivariate Cox regression analyses and Kaplan-Meier curves. The CLEC5A expression pattern in OC was validated using immunohistochemistry. The CIBERSORT algorithm was used to compare the immune cell landscape, and the results were validated in a GEO cohort. Finally, the predicted half maximal inhibitory concentration (IC50) values for five commonly used chemotherapy agents were also compared. Results: MiR-1825 level was higher in exosomes derived from OC cells and served as a tumor suppressor. The CLEC5A gene was found to be a target of miR-1825, the upregulation of which was correlated with a poor prognosis. M2 macrophage infiltration was significantly enhanced in the CLEC5A high expression group, while T follicular helper cell infiltration was reduced in it. While the predicted IC50 for cisplatin and doxorubicin was higher in the CLEC5A high expression group, that of docetaxel, gemcitabine, and paclitaxel was lower. Conclusion: MiR-1825, a promising OC biomarker, may promote OC progression by increasing CLEC5A expression via exosome-mediated efflux from tumor cells.  相似文献   

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Background: Establishing an appropriate prognostic model for PCa is essential for its effective treatment. Glycolysis is a vital energy-harvesting mechanism for tumors. Developing a prognostic model for PCa based on glycolysis-related genes is novel and has great potential. Methods: First, gene expression and clinical data of PCa patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and glycolysis-related genes were obtained from the Molecular Signatures Database (MSigDB). Gene enrichment analysis was performed to verify that glycolysis functions were enriched in the genes we obtained, which were used in non-negative matrix factorization (NMF) to identify clusters. The correlation between clusters and clinical features was discussed, and the differentially expressed genes (DEGs) between the two clusters were investigated. Based on the DEGs, we investigated the biological differences between clusters, including immune cell infiltration, mutation, tumor immune dysfunction and exclusion, immune function, and checkpoint genes. To establish the prognostic model, the genes were filtered based on univariable Cox regression, LASSO, and multivariable Cox regression. Kaplan–Meier analysis and receiver operating characteristic analysis validated the prognostic value of the model. A nomogram of the risk score calculated by the prognostic model and clinical characteristics was constructed to quantitatively estimate the survival probability for PCa patients in the clinical setting. Result: The genes obtained from MSigDB were enriched in glycolysis functions. Two clusters were identified by NMF analysis based on 272 glycolysis-related genes, and a prognostic model based on DEGs between the two clusters was finally established. The prognostic model consisted of LAMPS, SPRN, ATOH1, TANC1, ETV1, TDRD1, KLK14, MESP2, POSTN, CRIP2, NAT1, AKR7A3, PODXL, CARTPT, and PCDHGB2. All sample, training, and test cohorts from The Cancer Genome Atlas (TCGA) and the external validation cohort from GEO showed significant differences between the high-risk and low-risk groups. The area under the ROC curve showed great performance of this prognostic model. Conclusion: A prognostic model based on glycolysis-related genes was established, with great performance and potential significance to the clinical application.  相似文献   

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Cytoskeletal remodeling affects the shape, adhesion, and motility of cells. Cytoskeletal dynamics are modulated by matrix proteins, integrins, and several cytokines in the tumor microenvironment. In this scenario, signaling is activated by integrins and interferons, which can induce ISG15 gene expression. This gene encodes a ubiquitin-like protein that functions as a protein modifier via the ISGylation system. Furthermore, non-conjugated ISG15 acts as a cytokine-like protein. In this viewpoint, the interplay between free ISG15, protein ISGylation, and cytoskeletal dynamics in the tumor microenvironment is discussed.  相似文献   

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Metabolic reprogramming and immunologic suppression are two critical characteristics promoting the progression of head and neck squamous cell carcinoma (HNSCC). The integrative analysis of all the metabolism-related genes (MRGs) in HNSCC is lacking and the interaction between the metabolism and the immune characteristics also requires more exploration to uncover the potential mechanisms. Therefore, this study was designed to establish a prognostic signature based on all the MRGs in HNSCC. Genes of HNSCC samples were available from the TCGA and GEO databases while the MRGs were retrieved from a previous study. Ultimately 4 prognostic MRGs were selected to construct a model possessing robust prognostic value and accuracy in TCGA cohorts. The favorable reproducibility of this model was confirmed in validation cohorts from GEO databases. The risk score calculated by this model was an independent prognostic factor that further classified these HNSCC patients into high-/low-risk groups. GSEA analyses and somatic mutations indicated the low-risk group could activate several anti-tumor pathways and possessed lower TP53 mutation. The results of ESTIMATE, single-sample GSEA, CIBERSORT, and some immune-related molecules analyses suggested the low-risk group exhibited lower metabolic activities and higher immune characteristics. The Spearman correlation test implied most metabolic pathways with tumor-promoting function were negatively correlated with the immune activity, indicating a plausible approach of combining the anti-metabolism and the immunotherapy drugs in the high-risk group to enhance therapeutic effects than applied separately. In conclusion, this prognostic signature linking MRGs with the immune landscape could promote the individualized treatment for HNSCC patients.  相似文献   

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FRANCESCO MAININI 《Biocell》2021,45(5):1171-1173
Adoptive cell therapy and Immune Checkpoint Blockade Inhibitors have recently revolutionized the field of oncology. However, these types of immunotherapeutic approaches have limited success in treating solid tumors. In particular, chimeric antigen receptor (CAR)-T cells efficacy is hampered by immunosuppressive signals in the tumor microenvironment (TME) and by a limited infiltration of re-infused T cells to the tumor site. The field of nanobiotechnology applied to oncology is also rapidly expanding. Nanoparticles-based delivery systems can be employed to modulate the activity of immune cells present in the TME enhancing the efficacy of CAR-T cells. Interestingly, nano-backpacks can be attached to CAR-T cells prior to re-infusion to support their homing to the tumor site and to slowly release immunopotentiators directly in the TME. Furthermore, nanovaccines can also be employed to support the in vivo expansion of CAR-T cells with consequent enhancement of their therapeutic potential. In this viewpoint, recent advancement in the field of nanobiotechnology to support CAR-T cell therapy will be discussed. The development of novel therapeutic CAR-T cells protocols together with nanotherapies is warranted in order to take full advantage of the high therapeutic potential of CAR-T cell therapy.  相似文献   

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Oral Cancer (OC) is one of the most recurrent cancers in the head and neck squamous cancer (SCCHN)category. Recently, the genome-wide association studies (GWAS) have gained growing interest in the scientificcommunity. GWAS have identified several pathways involved in the interactions among general risk factors andgenomic variants affecting SCCHN. This systematic overview aims to critically evaluate the latest data reported withinthe scientific literature. The aim was to investigate the impact of genetic aspects on SCCHN onset and prognosis,involving other clinical and systemic co-factors. PubMed, Google Scholar, and Cancer Genetics Web databases havebeen systematically investigated for original articles published in the last two years, reporting studies on the mainqueries addressed in this work. This review also comparatively describes the impact of environmental andpathological co-factors in different types of cancers, clarifying and updating the role of genetic factors in SCCHNonset and development. The main outcomes reported may be helpful to drive clinicians towards their clinicalevaluations for the most appropriate therapeutic approach in SCCHN.  相似文献   

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KEWEI GAO  JIANGFENG HU  YI ZHOU  LIANG ZHU 《Biocell》2021,45(6):1521-1526
Increasing evidence proves that circular RNAs (circRNAs) play an important role in regulating the biological behaviors of tumors. The central purpose of this research was to investigate the functions of circRNA in gastric cancer. The utilization of real-time PCR was to test circPTN expression in gastric cancer cells. Cell counting colony formation assays, CCK-8 assay, and EdU assay were used to investigate proliferation. Transwell assay was applied to investigate migration. We discovered that circPTN was highly expressed in gastric cancer cells. Low expression of circPTN inhibits gastric cancer cell proliferation and migration. Elevated expression of circPTN promotes gastric cancer cell proliferation and migration. Moreover, we discovered that circPTN could accelerate self-renewal and increase the expression of stemness markers. The results of our study suggested that a high level of circPTN expression promotes the proliferation and stemness of gastric cancer cells.  相似文献   

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The peritoneum is the most common site of recurrence of gastric cancer (GC). Early occult peritonealmetastasis is difficult to detect by imaging examination. Stratifying the risk of peritoneal metastasis in patients withdifferent Lauren subtypes is of great clinical value. We performed a univariate Cox regression to identify those geneswith prognostic value of overall survival (OS) and peritoneal-specified disease-free survival (psDFS) from the GeneExpression Omnibus database. The candidate genes were screened by the Subpopulation Treatment Effect PatternPlot (STEPP) method. Propensity score matching (PSM) analysis was used to reduce the interference of confounderson the results. Based on the optimal cut-off values determined by the STEPP method, we found overexpression ofthree genes (HAND2-AS1, PRKAA2, and VLDLR) was correlated with shorter 1-year psDFS among patients withdiffuse-type than that of patients with intestinal-type GC, and it is highly significant. Gene Set Enrichment Analysis(GSEA) potentially suggested that the three genes promote the early occurrence of peritoneal metastasis in patientswith diffuse-type GC through glucose metabolism-related pathways. These three genes may be potential biomarkers.They can be used to assess the risk of peritoneal metastases to guide treatment decisions and follow-up strategies.  相似文献   

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Circulating tumor cells (CTCs) are crucial to tumor metastasis, and they usually undergo epithelial–mesenchymal transition (EMT) in order to disseminate from the primary tumor. However, very little is currentlyknown about the relationship between EMT and malignant phenotypes of CTCs in the context of gastric cancer.Therefore, this study aimed to investigate the contribution of EMT to malignant phenotypes of CTCs derived fromgastric cancer cells. We xenografted MKN28 gastric cancer cells pretreated with transforming growth factor-beta 1(TGFβ-1) into nude mice by intravenous injection. Next, we isolated CTCs from the blood of nude mice by gradientcentrifugation and found that CTCs derived from MKN28 cells pretreated with TGFβ-1 had a significantly increasedviability and invasion ability compared to MKN28 cells without TGFβ-1 treatment. Immunocytochemical stainingshowed lower expression of E-cadherin and higher expression of N-cadherin, vimentin, and β-catenin in CTCs derivedfrom MKN28 cells pretreated with TGFβ-1. Furthermore, the expression of Wnt3a, β-catenin, cyclin D1, and c-Mycwas significantly higher in CTCs derived from MKN28 cells pretreated with TGFβ-1. Taken together, these findingssuggest that TGFβ promotes EMT and malignant phenotypes of gastric cancer cells. Furthermore, the malignantphenotypes of gastric cancer cells induced by TGFβ are maintained in CTCs derived from these cells. Targeting EMT inCTCs is a new approach to the treatment of gastric cancer relapse and metastasis.  相似文献   

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模糊免疫PID调速系统及其在缝纫机上的仿真   总被引:1,自引:0,他引:1  
针对工业缝纫机采用传统PID调速方法无法满足其高动态性、高适应性的要求,借鉴生物免疫反馈机理,提出了模糊免疫PID控制方法,对永磁同步电动机(PMSM)进行了调速控制。通过研究遗传免疫算法和模糊控制算法,对传统的PID调速方法进行了改进,提出了模糊免疫PID调速控制模型,并且进行了仿真实验。仿真结果表明,与传统PID调速方法相比,该新型PID调速方法具有响应快速、超调量小、鲁棒性好、抗干扰能力强等优点。  相似文献   

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从核磁共振成像(MRI)对前列腺肿瘤的诊断入手,提出了一种基于两阶段集成支持向量机(SVM)的前列腺肿瘤辅助诊断方法。首先,提取MRI图像中的前列腺感兴趣区域(ROI)的统计特征、纹理特征和不变矩特征;然后,在不同的特征空间里,使用不同的核函数来扰动SVM参数并在不同的特征空间生成个体SVM,通过相对多数投票进行第一次集成;接着把第一次集成结果用相对多数投票进行第二次集成;最后,以前列腺患者的MRI图像为原始数据,采用两阶段融合集成SVM对前列腺肿瘤进行辅助诊断。实验显示,第一次集成分类准确率最高比单SVM提高了26.67%,第二次集成分类准确率比第一次集成SVM提高了3.33%,结果表明本文算法能够有效提高前列腺肿瘤的识别精度。  相似文献   

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Cervical cancer (CESC) is one of the most common cancers and affects the female genital tract. Consistent HPVinfection status has been determined to be a vital cause of tumorigenesis. HPV infection may induce changes to theimmune system and limit the host’s immune response. Immunotherapy is therefore essential to improving the overallsurvival of both locally advanced and recurrent CESC patients. Using 304 relevant samples from TCGA, we assessedimmune cell function in CESC patients to better understand the status of both tumor micro-environment cells andimmune cells in CESC. Functional enrichment analysis, pathway enrichment analysis, and PPI network constructionwere performed to explore the differentially expressed genes (DEGs). The analysis identified 425 DEGs, whichincluded 295 up-regulated genes and 130 down-regulated genes. We established that upregulation of CCL5 wascorrelated with significantly better survival, meaning that CCL5 expression could serve as a novel prognosticbiomarker for CESC patients. We further focused on CCL5 as a hub gene in CESC, as it had significant correlationswith increased numbers of several types of immune cells. Cell-type fractions of M1 macrophages were significantlyhigher in the high-immune-scores group, which was associated with better overall survival. Finally, we concluded thatCCL5 is a promising prognostic biomarker for CESC, as well as a novel chemotherapeutic target.  相似文献   

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