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1.
Hepatocellular carcinoma (HCC) is a common immunogenic malignant tumor. Although the new strategies of immunotherapy and targeted therapy have made considerable progress in the treatment of HCC, the 5-year survival rate of patients is still very low. The identification of new prognostic signatures and the exploration of the immune microenvironment are crucial to the optimization and improvement of molecular therapy strategies. We studied the potential clinical benefits of the inflammation regulator miR-93-3p and mined its target genes. Weighted gene co-expression network analysis (WGCNA), univariate and multivariate COX regression and the LASSO COX algorithm are employed to identify prognostic-related genes and construct multi-gene signature-based risk model and nomogram for survival prediction. Support vector machine (SVM) based Cibersort’s deconvolution algorithm and gene set enrichment analysis (GSEA) is used to evaluate the changes in tumor immune microenvironment and pathway differences. The study found the favorable prognostic performance of miR-93-3p and identified 389 prognostic-related target genes. The risk model based on a novel 5-gene signature (cct5, cdk4, cenpa, dtnbp1 and flvcr1) was developed and has prominent prognostic significance in the training cohort (P < 0.0001) and validation cohort (P = 0.0016). The nomogram constructed by combining the gene signature and the AJCC stage further improves the survival prediction ability of the gene signature. The infiltration level of multiple immune cells (especially T cells, B cells and macrophages) were positively correlated with the expression of prognostic signature. In addition, we found that gene markers of T cells and B cells is monitored and regulated by prognostic signature. Meanwhile, several GSEA pathways related to the immune system are enriched in the high-risk group. In general, we integrated the WGCNA, LASSO COX and SVM algorithms to develop and verify 5-gene signatures and nomograms related to immune infiltration to improve the survival prediction of patients. 相似文献
2.
ZECHAO LU FUCAI TANG HAOBIN ZHOU ZEGUANG LU WANYAN CAI JIAHAO ZHANG ZHICHENG TANG YONGCHANG LAI ZHAOHUI HE 《Biocell》2023,47(2):339-350
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
3.
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
4.
LU YANG YUN LIU BOKE ZHANG MENGSI YU FEN HUANG YANG WEN JIANGZHENG ZENG YANDA LU CHANGCHENG YANG 《Biocell》2022,46(5):1215-1243
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
5.
Cancer remains to be one of the most severe sicknesses globally. Cases have kept rising over the years. Breast cancer (BC), which is among the leading types of cancers and predominantly affects women, is the second leading cause of cancer mortality. Researchers have developed interventions over the years; however, the BC survival rate has not improved since the 1980s. This has created the need for novel drug interventions that would manage and treat BC more effectively. This study focused on using a combination of natural product extracts such as phytoestrogen (Ziziphus jujube) and Tannin nanoparticles (NP99) together, which we have referred to as (Z.NP99) and tamoxifen (Tam) as one of the leading BC drugs since the 70s, in treating BC. The effectiveness of Tam if used alone in the treatment and if combined with Z.NP99 was evaluated using MCF-7 cells in vitro. The findings showed that the combination treatment of Z.NP99 affected the proliferation and viability of MCF-7 cells more than Tam at a 10 μg/mL dose. Moreover, Z.NP99 with Tam stimulated the maximum reduction of MCF-7 proliferation and viability in a time-dependent manner. Furthermore, Tam and Z.NP99 augmented the DNA fragmentation percentage combined with the upregulation of the apoptotic genes. Additionally, the results showed that the apoptotic impact of Z.NP99 and Tam on MCF-7 cells may be intermediated by down-regulating some genes such as Claudin-1 followed by down-regulating mRNA expression of MMP-9, VEGF, and BCL-2 genes of treated cells. Combining Tam with Z.NP99 considerably enhanced the effectiveness of conventional therapy. As a result, this study suggested that the Z.NP99 was ideal for developing effective natural treatments that would improve BC outcomes. 相似文献
6.
LETIAN JIN HETING CHEN QI RUAN RUI LIU YIFENG FAN XIUFANG XU DAJIANG WANG JIAHUI LU 《Biocell》2023,47(7):1483-1498
During the chemotherapy of tumors, the cytotoxic effect of drugs is vital to kill tumor cells, and the delivery of a chemotherapeutic agent is of great importance for optimal therapeutic effects. The high in vivo clearance rate and low delivery efficiency of conventional chemotherapeutic agents affect the therapeutic effect. In recent years, the responsive drug delivery nanosystem has received increasing concern owing to its excellent biocompatibility, stable delivery performance, and controlled drug release strategies. To lucidly explain the cytocidal and immunotherapeutic effects of such responsive nanosystems in breast cancer, this review discusses the various stimuli and responses of drug-loaded liposomal nanosystems. The light/magnetic response of drug-loaded bionic membranes nanosystems and the heat/magnetic response of drug-loaded iron oxide nanosystems are also elaborated. Their cancer cell-killing efficacy and antitumor immunotherapeutic effects are also scrutinized. 相似文献
7.
流式细胞技术(FCM)在人乳腺癌耐药细胞系耐药逆转研究中的应用 总被引：2，自引：1，他引：2
目的:人乳腺癌耐药细胞系(MCF-7/ADR)经不同逆转方法作用后,对耐药逆转结果进行检测,寻找最佳逆转方法。方法:用流式细胞仪,分别对MCF-7及经不同逆转剂作用后MCF-7/ADR进行检测。结果:经流式细胞仪检测,P-170表达:MCF-7为11.4％,MCF-7/ADR为99.2％,不同逆转剂作用细胞后各实验组P-170表达均大幅度下降。经PI染色后,不同逆转剂逆转MCD-7/ADR的细胞周期无明显变化。结论:异博定结合干扰素及加温的方法,逆转效果最佳。 相似文献
8.
C2- and C4-position 17β-estradiol metabolites play an important role in breast carcinogenesis. 2-Hydroxyestradiol and 4-hydroxyestradiol are implicated in tumorigenesis via two pathways. These pathways entail increased cell proliferation and the formation of reactive oxygen species that trigger an increase in the likelihood of deoxyribonucleic acid mutations.
2-Methoxyestradiol, a 17β-estradiol metabolite, however, causes induction of apoptosis in transformed and tumor cells; thus exhibiting an antiproliferative effect on tumor growth. The 4-hydroxyestradiol:2- methoxyestradiol and 2-hydroxyestradiol:2-methoxyestradiolratios therefore ought to be taken into account as possible indicators of carcinogenesis. 相似文献
2-Methoxyestradiol, a 17β-estradiol metabolite, however, causes induction of apoptosis in transformed and tumor cells; thus exhibiting an antiproliferative effect on tumor growth. The 4-hydroxyestradiol:2- methoxyestradiol and 2-hydroxyestradiol:2-methoxyestradiolratios therefore ought to be taken into account as possible indicators of carcinogenesis. 相似文献
9.
肿瘤一直以来就是人类难以攻克的顽疾,近年来肿瘤疾病的爆发数量呈现上升趋势,如今我国肿瘤病例数约占全世界病例数的55%。实时荧光定量PCR技术(Real-Time PCR)是一种通过检测PCR产物中荧光讯号的强度从而进行定量的技术,这实现了对核酸信息量的分析比较。相对于常规的定性PCR技术,其具有检测范围宽、检测灵敏度高、精密度高、特性强、定量准确、重现性好等优点,现今已被广泛应用于生物学领域及医学领域尤其是肿瘤的早期诊断、分型、分期、预后诊断等。本文概述了实时荧光定量PCR技术的基本原理及其在肿瘤检测中的应用,并探讨了该技术的发展现状和应用前景。 相似文献
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目的分析靶控输注舒芬太尼和丙泊酚对乳腺癌根治术患者的麻醉效果。方法选取择期行乳腺癌根治术患者60例,随机分为观察组和对照组（n=30）,观察组靶控输注3ug/mL丙泊酚和0.3ng/mL舒芬太尼,对照组微量泵持续泵注入3ug/mL丙泊酚和4ng/mL瑞芬太尼。结果观察组在插管2min时的HR及MAP与靶控平衡时无显著差异（P〉0.05）;对照组在插管5min时的HR及MAP显著高于靶控平衡时（P〈0.05）;插管后,观察组的BIS值显著低于对照组（P〈0.05）;观察组的苏醒质量明显优于对照组,且不良反应率较低（P〈0.05）。结论靶控输注舒芬太尼和丙泊酚能更好地维持乳腺癌患者手术麻醉诱导时的血流动力学平衡,不良反应少,且可增强丙泊酚所具有的镇静作用。 相似文献
11.
目的:探讨乳腺癌组织中Her-2及ALDH1的表达相关性及其临床意义。方法:选取105例原发性乳腺癌标本。采用免疫组化法检测Her-2、ALDH1蛋白的表达,并结合临床病理特征进行相关性分析和无病生存期分析。结果:(1)Her-2与ALDH1在乳腺癌中的表达率分别为29.52%、66.67%。(2)乳腺癌原发灶中Her-2蛋白的表达与肿瘤大小、ER呈正相关(P≤0.05),与年龄、民族、组织学分期及病理类型、PR均无相关性(P>0.05)。ALDH1蛋白表达与年龄、民族、组织学分期及病理类型、肿瘤大小、淋巴结转移、ER、PR均未发现有相关性(P>0.05)。(3)Her-2与ALDH1在乳腺癌表达中呈正相关(r=0.192,P≤0.05)。(4)Her-2高表达患者2年无病生存率显著低于Her-2阴性患者(P<0.05),ALDH1阳性患者与阴性患者2年无病生存期无明显差异(P>0.05)。(5)COX回归模型分析结果显示Her-2是影响患者预后的独立因素(P=0.008)。Her-2的相对危险度=6.284>1。结论:ALDH1与Her-2在乳腺癌组织中的表达呈正相关。Her-2表达与乳腺癌术后患者预后呈负相关,而ALDH1表达与乳腺癌术后患者的预后无明显相关性。 相似文献
12.
Index for spatial heterogeneity in breast cancer 总被引：1，自引：0，他引：1
V. SHARIFI-SALAMATIAN B. PESQUET-POPESCU† J. SIMONY-LAFONTAINE‡ & J. P. RIGAUT 《Journal of microscopy》2004,216(2):110-122
Histopathological heterogeneity in cancer is a general concern. Breast carcinoma heterogeneity is now widely admitted as a source of histological grading imprecision and reproducibility problems. Classically, homogeneity is defined as equivalent to stationarity. A measure of heterogeneity based on asymptotic properties of spatial statistics is developed. Long‐range dependences in heterogeneous spatial processes make estimation of the proposed heterogeneity measure unreliable. A robust estimator based on the wavelet transform is presented; this bypasses long‐range dependences. The estimator extends previous works on one‐dimensional stochastic processes to two dimensions as appropriate for histopathological analysis. As a side result, the estimator gives confidence intervals for the heterogeneity measure that enables the formulation and validation of testable hypothesis on the observed histopathological samples. This approach is applied to the characterization of breast cancer tumours. We show that the heterogeneity measure for various blocks of a single tumour is invariable, even when various blocks differ in size and in number of marked nuclei. 相似文献
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ALAN CN DE MORAES CHERLEY BV ANDRADE CAMILA SALATA ANA LR NASCIMENTO ISALIRA P RAMOS REGINA CS GOLDENBERG JORGE J CARVALHO ANA CS MACHADO 《Journal of microscopy》2016,261(3):267-276
Some chemotherapeutic agents used for breast cancer (BC) treatment can induce severe side effects in the ovarian tissue. The combination of cyclophosphamide and docetaxel (TC) is widely used for BC treatment; however, its late effects in the ovary are not completely understood. The main purpose of this study was to evaluate the structural and ultrastructural alterations in the ovarian stroma induced by TC treatment. Wistar rats were divided into two groups: a control group and a TC group. They were euthanized 5 months after the end of treatment, and their plasma and ovaries were collected. Important alterations were noted. The serum estradiol level was significantly reduced in the TC group compared with the control group. Additionally, the number of apoptotic nuclei was higher in the TC group. The role of the inflammatory response in the development of ovarian damage was investigated, and we found an increased number of mast cells and increased expression of TNF‐α in the TC group. The involvement of fibrosis was also investigated. The results showed that the TC group had increased expression levels of TGF‐β1, collagen type I (col‐I) and collagen type III (col‐III) compared with the control group. Ultrastructural analysis revealed the presence of collagen fibrils in the treated group and illustrated that the ovarian tissue architecture was more disorganized in this group than in the control group. The results from this study are important in the study of chemotherapy‐induced ovarian failure and provide further insight into the mechanisms involved in the development of this disease. 相似文献
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C. J. Cornelisse A. M. J. van Driel-Kulker F. Meyer J. S. Ploem 《Journal of microscopy》1985,137(1):101-110
In order to develop an objective grading system for nuclear atypia in breast cancer, an image analysis technique has been applied for the automated recognition of enlarged and hyperchromatic nuclei in cytology specimens. The image segmentation algorithm, based on the ‘top hat’ image transformation developed in mathematical morphology, is implemented on the LEYTAS automated microscope system. The performance of the segmentation algorithm has been evaluated for fifty malignant and eighty-five benign breast lesions by visual inspection of the displayed ‘flagged’ objects. The mean number of flagged objects per 1600 image fields for breast cancers was 887 (range 0–7920) of which 87% consisted of single, atypical nuclei. For benign lesions the mean number was 30 (range 0–307) of which 20% were single nuclei. By adaptation of the ‘top hat’ parameter values, a more extreme subpopulation of atypical nuclei could be discriminated. The large interspecimen variation in the breast cancer results was related to differences in DNA content distribution and mean nuclear area, determined independently with scanning cytophotometry, and to some extent with the histological type. 相似文献
17.
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
18.
Hepatocellular carcinoma (HCC) is a worldwide malignant tumor that caused irreversible consequences. Tanshinone IIA has been shown to play a notable role in HCC treatment. However, the potential targets and associating mechanism of Tanshinone IIA against HCC remain unknown. We first screened out 105 overlapping genes by integrating the predicted targets of Tanshinone IIA from multiple databases and the differentially expressed genes of HCC from the Cancer Genome Atlas (TCGA) database. Then, we performed weighted gene co-expression network analysis (WGCNA) using the RNA-seq profiles of overlapping genes and HCC-related clinical information. 23 genes related to clinical tumor grade in the important module were imported for Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) analysis. Comparing the key genes in the important module from WGCNA with the high connectivity nodes from the PPI network, we identified three hub genes, AURKB, KIF11, and PLK1. For further verification, we tested the binding of Tanshinone IIA to three hub genes. The survival curve, receiver operating characteristic (ROC) curve, mRNA expression, and protein expression were also used to validate the hub genes. In the study, WGCNA revealed grade-specific gene modules, and the following KEGG pathway analysis indicated that Tanshinone IIA probably plays therapeutical effect in the development of HCC, especially in the cell cycle. Our result partially explained the pharmacological mechanism of Tanshinone IIA against HCC. 相似文献
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《Measurement》2016
A lot of studies confirmed the seriousness of breast cancer as the most tumors lethal to women worldwide. Early detection and diagnosis of breast cancer are of great importance to increase treatment options and patients’ survival rate. Ultrasound is one of the most frequently used methods to detect and diagnosis breast tumor due to its harmlessness and inexpensiveness. However, problems were found in the tumor diagnosis and classification as benign and malign on ultrasound image for its vagueness, such as speckle noise and low contrast. In this paper, we propose a novel breast tumor classification algorithm that combines texture and morphologic features based on neutrosophic similarity score. Then, a supervised feature selection technique is employed to reduce feature space. Finally, a support vector machine (SVM) classifier is employed to prove the discrimination power of the proposed features set. The proposed system is validated by 112 cases (58 malign, 54 benign). The experimental results show that such features set is promising and 99.1% classification accuracy is achieved. 相似文献