Growing evidence has shown that a large number of miRNAs are abnormally expressed in cervical cancer (CC) tissues and play irreplaceable roles in tumorigenesis, progression, and metastasis. This study aimed to identify new biomarkers and pivotal genes associated with CC prognosis through comprehensive bioinformatics analysis. At first, the data of gene expression microarray (GSE30656) was downloaded from GEO database and differential miRNAs were obtained. Additionally, 4 miRNAs associated with the survival time of patients with CC were screened through TCGA differential data analysis, Kaplan-Meier, and Landmark analysis. Among them, the low expression of miR-188 and high expression of miR-223 correlated with the short survival of CC patients, while the down-regulation of miR-99a and miR-125b was closely related to the 5-year survival rate of patients. Then, based on the correspondence between the differentially expressed genes (DEGs) in CC from the TCGA data and the 4 miRNAs target genes, 58 target genes were screened to perform the analysis of function enrichment and the visualization of protein-protein interaction (PPI) networks. The seven pivotal genes of the PPI network as the target genes of four miRNAs related to prognosis, they were directly or indirectly involved in the development of CC. In this study, based on high-throughput data mining, differentially expressed miRNAs and related target genes were analyzed to provide an effective bioinformatics basis for further understanding of the pathogenesis and prognosis of CC. And the results may be a promising biomarker for the early screening of high-risk populations and early diagnosis of cervical cancer.
Background . Lung squamous cell carcinoma (LUSC) is a subtype of highly malignant lung cancer with poor prognosis, for which smoking is the main risk factor. However, the underlying genetic and molecular mechanisms of smoking-related LUSC remain largely unknown. Methods . We mined existing LUSC-related mRNA, miRNA, and lncRNA transcriptome data and corresponding clinical data from The Cancer Genome Atlas (TCGA) database and divided them into smoking and nonsmoking groups, followed by differential expression analysis. Functional enrichment analysis of the unique differentially expressed mRNAs of the two groups was performed using the DAVID database. Subsequently, the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network of LUSC in smoking and nonsmoking groups was constructed. Finally, survival analyses were performed to determine the effects of differentially expressed lncRNAs/mRNAs/miRNAs that were involved in the ceRNA network on overall survival and to discover the hub genes. Results . A total of 1696 lncRNAs, 125 miRNAs, and 3246 mRNAs and 1784 lncRNAs, 96 miRNAs, and 3229 mRNAs with differentially expressed profiles were identified in the smoking and nonsmoking groups, respectively. The ceRNA network and survival analysis revealed four lncRNAs (LINC00466, DLX6-AS1, LINC00261, and AGBL1), one miRNA (hsa-mir-210), and two mRNAs (CITED2 and ENPP4), with the potential as biomarkers for smoking-related LUSC diagnosis and prognosis. Conclusion . Taken together, our research has identified the differences in the ceRNA regulatory networks between smoking and nonsmoking LUSC, which could lay the foundation for future clinical research.
Abstract Background/purpose Cancer immunotherapy has revolutionized the clinical treatment of several tumors. Immune infiltration has been found to be closely related to clinical prognosis, but it shows limited activity in breast cancer (BC). Therefore, this study aimed to explore the infiltration pattern of immune cells in BC, and to find potential prognostic markers and new therapeutic targets.Patients and methods We downloaded the immune genome data of BC from the Cancer Genome Atlas (TCGA), and analyzed the tumor- infiltrating immune cells (TIICs) in BC for the first time using the CIBERSORT algorithm. The aim of this study was to assess the proportions of 22 immune cell subsets in BC and examine the correlation between each TIIC and overall survival (OS) as well as clinical characteristics.Results The results indicated that: (1) there was a significant difference between the immune infiltration spectrum of cancerous and adjacent tissues, with M2 macrophages, M0 macrophages, and CD4 + T cells being highly expressed in BC; (2) CD8 + T cells were positively correlated with activated CD4 + memory T cells and negatively correlated with M0 macrophages, and M2 macrophages was inversely correlated with M1 macrophages, T cells regulatory, T cells CD8; (3) T cells, macrophages and BC TNM stage, age, clinical stage were correlated (P < 0.05); and (4) high expression of M2 macrophage markers could be an independent biomarker of poor prognosis and a potential therapeutic target for BC.Conclusion This study provides a new research method for the systematic study of immune cells in the BC tumor microenvironment, and provides theoretical guidance for further experiments to verify M2 macrophages and T cell subsets as a potential target for immunotherapy and prognosis.
Abstract Purpose Breast cancer (BC) remains a serious health threat for women due to its high incidence and the trend of rejuvenation. Accumulating evidence has highlighted that microRNAs (miRNAs) and messenger RNAs (mRNAs) could play important roles in various biological processes involved in the pathogenesis of BC. The present study aimed to identify potential prognostic biomarkers associated with BC. Methods Here, original gene expression profiles of patients with BC was downloaded from The Cancer Genome Atlas (TCGA) database. TargetScan, miRDB, and miRTarBase databases were used to predict the target genes of prognostic‐related differentially expressed miRNAs (DEMs). Subsequently, functional enrichment analysis and topological analysis were performed on the overlaps of target genes and differentially expressed mRNAs (DEGs), and Kaplan‐Meier analysis was used to predict prognosis‐related target genes to identify prognostic biomarkers. Results A total of 218 DEMs and 2222 DEGs were extracted in which eight miRNAs were associated with prognosis, and 278 target DEGs were screened out incorporated into functional enrichment analysis and protein‐protein interaction network visualization studies. Additionally, five hub genes (CXCL12, IGF1, LEF1, MMP1, and RACGAP1) were observed as potential biomarkers for BC prognosis through survival analysis. Conclusion We performed a distinctive correlation analysis of miRNA‐mRNA in BC patients, and identified eight miRNAs and five hub genes may be effective biomarkers for the prognosis of BC patients.
Abstract The confined groundwater of arid sedimentary plains has been disturbed by long‐term anthropogenic extraction, and its hydrochemical quality is required for sustainable development. The present research investigates the hydrochemical characteristics, formation, potential health threats, and quality suitability of the confined groundwater in the central North China Plain. Results show that the confined groundwater has a slightly alkaline nature in the study area, predominantly dominated by fresh‐soft Cl‐Na and HCO 3 ‐Na types. Water chemistry is governed by water–rock interactions, including dissolution of evaporites and cation exchange. Approximately 97% of the sampled confined groundwaters exceed the prescribed standard for F − . It is mainly due to geological factors such as mineral dissolution, cation exchange, and competitive adsorption of HCO 3 − and may also be released from compacted soils because of groundwater extraction. Enriched F − in the confined groundwater can pose an intermediate and higher non‐carcinogenic risk to more than 90% of the population. It poses the greatest health threat to the population in the north‐eastern part of the study area, especially to infants and children. For sustainable development, the long‐term use of confined groundwater for irrigation in the area should be avoided, and attention should also be paid to the potential soil salinization and infiltration risks. In the study area, 97% of the confined groundwaters are found to be excellent or good quality for domestic purposes based on Entropy‐weighted Water Quality Index. However, the non‐carcinogenic health risk caused by high contents of F − cannot be ignored. Therefore, it is recommended that differential water supplies should be implemented according to the spatial heterogeneity of confined groundwater quality to ensure the scientific and rational use of groundwater resources. Practitioner Points The hydrochemistry quality of confined groundwater in an arid sedimentary plain disturbed by long‐term anthropogenic extraction was investigated. The suitability of confined groundwater for multiple purposes such as irrigation and drinking were evaluated. The hydrochemical characteristics and formation mechanism of confined groundwater under the influence of multiple factors were revealed.
Tumor microenvironment (TME) cells constitute a vital element of tumor tissues. Increasing evidence has shown that immune response in the microenvironment plays an active role in tumor invasion, metastasis, and recurrence, and is an important factor affecting tumor prognosis. Our study aimed to identify the gene signatures in lung adenocarcinoma (LUAD) microenvironment for prognosis and immunotherapy.In this study, we evaluated, for the first time, the stromal and immune scores of 594 patients from The Cancer Genome Atlas (TCGA) database with LUAD using the ESTIMATE algorithm. Three hundred and sixty-seven dysregulated immune-related genes were identified. Then, we performed functional enrichment analysis of these genes, and found the best gene model and construct the signature through univariate, Lasso and multivariate COX regression analysis. To assess the independently prognostic ability of the signature, the Kaplan-Meier survival analysis and Cox's proportional hazards model were performed.Functional enrichment analysis and protein-protein interaction networks showed that the immune-related genes mainly played a role in immune response, activation/proliferation of immune-related cells, and chemokine activity. A prognostic model involving 6 genes was constructed and the signature was identified as an independent prognostic factor and significantly associated with the overall survival (OS) of LUAD. The area under curve (AUC) of the receiver operating characteristic curve (ROC curve) for the 6 genes signature in predicting the 3-year survival rate was 0.708. Finally, four genes (FOXN4, KLHL4, FAM83F and CCR2) can be used as candidate prognostic biomarkers for LUAD.Our findings will help evaluate the prognosis of LUAD and provide new ideas for exploring the potential relationship between TME and LUAD treatment and prognosis.
Qingdai, a traditional Chinese medicine (TCM) used for the treatment of chronic myeloid leukemia (CML) with good efficacy, has been used in China for decades. However, due to the complexity of traditional Chinese medicinal compounds, the pharmacological mechanism of Qingdai needs further research. In this study, we investigated the pharmacological mechanisms of Qingdai in the treatment of CML using network pharmacology approaches. First, components in Qingdai that were selected by pharmacokinetic profiles and biological activity predicted putative targets based on a combination of 2D and 3D similarity measures with known ligands. Then, an interaction network of Qingdai putative targets and known therapeutic targets for the treatment of chronic myeloid leukemia was constructed. By calculating the 4 topological features (degree, betweenness, closeness, and coreness) of each node in the network, we identified the candidate Qingdai targets according to their network topological importance. The composite compounds of Qingdai and the corresponding candidate major targets were further validated by a molecular docking simulation. Seven components in Qingdai were selected and 32 candidate Qingdai targets were identified; these were more frequently involved in cytokine-cytokine receptor interaction, cell cycle, p53 signaling pathway, MAPK signaling pathway, and immune system-related pathways, which all play important roles in the progression of CML. Finally, the molecular docking simulation showed that 23 pairs of chemical components and candidate Qingdai targets had effective binding. This network-based pharmacology study suggests that Qingdai acts through the regulation of candidate targets to interfere with CML and thus regulates the occurrence and development of CML.
Abstract Acute myeloid leukemia (AML) is a heterogeneous clonal neoplasm characterized by complex genomic alterations. The incidence of AML increases with age, and most cases experience serious illness and poor prognosis. To explore the relationship between abnormal DNA methylation and the occurrence and development of AML based on the Gene Expression Database (GEO), this study extracted data related to methylation in AML and identified a methylated CpG site that was significantly different in terms of expression and distribution between the primary cells of AML patients, and hematopoietic stem/progenitor cells from normal bone marrow. To further investigate the differences caused by the dysfunction of methylation sites, bioinformatics analysis was used to screen methylation‐related biomarkers, and the potential prognostic genes were selected by univariate and multivariate Cox proportional hazards regressions. Finally, five independent prognostic indicators were identified. In addition, these results provide new insight into the molecular mechanisms of methylation.
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