Significant role of PPP3CB in malignant gliomas development, prognosis and potential therapeutic application-a study based on comprehensive bioinformatics, cell experiments and immunohistochemistry analyses.

Introduction: Malignant gliomas are the most prevalent and fatal types of primary malignant brain tumors with poor prognosis. Protein phosphatase 3 catalytic subunit beta (PPP3CB) is a pivotal constituent of the Ca2+/calmodulin-dependent serine/threonine protein phosphatases and widely expressed in brain. We aimed at identifying whether PPP3CB has potential in being a novel biomarker of malignant gliomas, bringing new insights to clinical management and therapy. Methods: Transcriptomes and clinical data of Glioblastoma (GBM) and low-grade glioma (LGG) samples were downloaded from TCGA and CGGA. We first explored the expressional and survival features of tumor tissues. Then, PPP3CB-associated genes were identified and their functional pathways were explored through GSEA analyses. Western blotting was conducted to modify PPP3CB expression. Samples of glioma patients and healthy controls were collected and immunohistochemistry (IHC) staining was performed to detect protein level. Further, we carried out an immune infiltration analysis, explored the correlation between PPP3CB and immune checkpoint genes, as well as to assessed the tumor mutation burden (TMB) and tumor microenvironment score (TMEscore) of PPP3CB. Results: PPP3CB expression in malignant glioma tissues was significantly downregulated and was considered an independent prognostic factor. Several functional pathways were observed through functional pathway analyses. PPP3CB's expression was strongly related to the infiltration of various immune cells and expression of key immune checkpoint genes. PPP3CB expression in high-grade gliomas was significantly lower, affecting glioma cells' proliferation and apoptosis in vitro. Conclusion: PPP3CB was a potential biomarker for the diagnosis and prognosis of malignant gliomas.

Emerging Role of Circular RNAs in the Pathogenesis of Retinoblastoma.

Retinoblastoma (Rb) accounts for 3% of all childhood cancers. It is the most common intraocular malignant tumor with a highly aggressive and metastatic phenotype. Gaining a more comprehensive understanding of the molecular mechanisms underlying the proliferation, metastasis, migration, invasive apoptosis, and autophagy processes associated with this cancer would facilitate the design of therapeutic modalities and the identification of novel tumor markers. Recent investigations have shown the contribution of circular RNAs (circRNAs) in the evolution of Rb. Several circRNAs, including circ_0000034, circ_0000527, circ_0075804, circ_0099198, circFAM158A, and circVAPA, promote the progression and metastasis of Rb. However, some circRNAs, such as circ_0001649, circMKLN1, and circTET1, play a tumor suppressive role. In this regard, circRNAs can regulate cancer-developing processes including cell proliferation, apoptosis, migration, invasion, and tumor growth. This review summarizes the functional roles of circRNAs in Rb and their potential clinical applications for diagnosis and prognosis, and provides a comprehensive understanding of the role of circRNAs in the pathophysiology of Rb.

Effect of Air Pollution on Heart Failure: Systematic Review and Meta-Analysis.

BACKGROUND: Heart failure (HF) poses a significant global disease burden. The current evidence on the impact of air pollution on HF remains inconsistent. OBJECTIVES: We aimed to conduct a systematic review of the literature and meta-analysis to provide a more comprehensive and multiperspective assessment of the associations between short- and long-term air pollution exposure and HF from epidemiological evidences. METHODS: Three databases were searched up to 31 August 2022 for studies investigating the association between air pollutants (PM2.5, PM10, NO2, SO2, CO, O3) and HF hospitalization, incidence, or mortality. A random effects model was used to derive the risk estimations. Subgroup analysis was conducted by geographical location, age of participants, outcome, study design, covered area, the methods of exposure assessment, and the length of exposure window. Sensitivity analysis and adjustment for publication bias were performed to test the robustness of the results. RESULTS: Of 100 studies covering 20 countries worldwide, 81 were for short-term and 19 were for long-term exposure. Almost all air pollutants were adversely associated with the risk of HF in both short- and long-term exposure studies. For short-term exposures, we found the risk of HF increased by 1.8% [relative risk (RR)=1.018, 95% confidence interval (CI): 1.011, 1.025] and 1.6% (RR=1.016, 95% CI: 1.011, 1.020) per 10-µg/m3 increment of PM2.5 and PM10, respectively. HF was also significantly associated with NO2, SO2, and CO, but not O3. Positive associations were stronger when exposure was considered over the previous 2 d (lag 0-1) rather than on the day of exposure only (lag 0). For long-term exposures, there were significant associations between several air pollutants and HF with RR (95% CI) of 1.748 (1.112, 2.747) per 10-µg/m3 increment in PM2.5, 1.212 (1.010, 1.454) per 10-µg/m3 increment in PM10, and 1.204 (1.069, 1.356) per 10-ppb increment in NO2, respectively. The adverse associations of most pollutants with HF were greater in low- and middle-income countries than in high-income countries. Sensitivity analysis demonstrated the robustness of our results. DISCUSSION: Available evidence highlighted adverse associations between air pollution and HF regardless of short- and long-term exposure. Air pollution is still a prevalent public health issue globally and sustained policies and actions are called for to reduce the burden of HF. https://doi.org/10.1289/EHP11506.

[Salidroside alleviates retinopathy in diabetes rats by inhibiting oxidative stress and immune inflammation through activating PI3K/AKT pathway].

Objective To investigate the ameliorative effect of salidroside on diabetes retinopathy (DR) rats and its mechanism. Methods Male SD rats were randomly divided into blank group, model group, low-dose and high-dose salidroside treatment groups. Except for the blank group, other groups were modeled by intraperitoneal injection of streptozotocin. After successful modeling, treatment groups were injected intraperitoneally with [50 mg/(kg.d)] and [100 mg/(kg.d)] salidroside respectively, for 4 weeks; the blank group and model group were injected with corresponding doses of saline. ELISA was used to measure the expression levels of antioxidant-related enzyme activity and inflammatory factors in blood glucose and serum of rats in each group. Retinal tissue lesions were detected by HE staining, and the expression of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM-1) in retinal tissues were detected by immunohistochemical staining. Western blot analysis was used to detect the expression of phosphatidylinositol 3 kinase (PI3K) , nuclear factor κB p65 (NF-κB p65), phosphorylated p38 MAPK (p-p38 MAPK), and phosphorylated protein kinase B (p-AKT) proteins. Results Compared with model group, salidroside could significantly reduce blood glucose level and increase body mass in DR rats. The serum levels of superoxide dismutase (SOD) and catalase (CAT) were significantly increased, while the levels of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and IL-1ß were reduced. The protein expression of VEGF, ICAM-1, NF-κB p65 and p-p38 MAPK was significantly decreased, while the protein expression of PI3K and p-AKT was increased. Conclusion Salidroside can reduce DR in rats by inhibiting oxidative stress and immune inflammatory response, which may be related to the reduction of abnormal expression of VEGF and ICAM-1 and the activation of PI3K/AKT signaling pathway.

Ocular Phenotypes in Patients With Hemophagocytic Lymphohistiocytosis: A Retrospective Analysis in a Single Center Over 7 Years.

PURPOSE: To investigate the presence and type of ocular abnormalities in patients with hemophagocytic lymphohistiocytosis (HLH). DESIGN: A retrospective cross-sectional study. METHODS: Observational report of ocular findings and their associations with age, sex, underlying disease, and hematologic parameters. HLH was defined according to the 2004 criteria, and the patients were enrolled from March 2013 to December 2021. Analysis began in July 2022 and ended in January 2023. The main outcome measures were ocular abnormalities associated with HLH and their potential risk factors. RESULTS: Of 1525 HLH patients, 341 had ocular examinations, and 133 (133 of 341, 39.00%) had ocular abnormalities. Mean age at presentation was 30.21 ± 14.42 years. The multivariate analysis indicated that old age, autoimmune disorders, decreasing red blood cell count, decreasing platelet count, and increasing fibrinogen level were independent risk factors of ocular involvement in HLH patients. The most common presenting ocular findings were posterior segment abnormalities (66 patients, 49.62%), including retinal and vitreous hemorrhage, serous retinal detachment, cytomegalovirus retinitis, and optic disc swelling. Other HLH-associated ocular abnormalities included ocular surface infection (conjunctivitis, 34 patients, 25.56%; keratitis, 16 patients, 12.03%), subconjunctival hemorrhage (11 patients, 8.27%), chemosis (5 patients, 3.76%), anterior uveitis (11 patients, 8.27%), glucocorticoid-induced glaucoma (5 patients, 3.76%), radiation cataract (1 patient, 0.75%), dacryoadenitis (2 patients, 1.50%), dacryocystitis (1 patients, 0.75%), orbital cellulitis (2 patients, 1.50%), orbital pseudotumor (2 patients, 1.50%), and strabismus (2 patients, 1.50%). CONCLUSIONS: Eye involvement is not uncommon in HLH. Better awareness among both ophthalmologists and hematologists is necessary for prompt diagnosis and institution of appropriate management strategies with potential to save sight and life.

Median nerve stimulation elevates ventricular fibrillation threshold via the cholinergic anti-inflammatory pathway in myocardial infarction canine model.

Background: Median nerve stimulation (MNS) diminishes regional myocardial ischemia and ventricular arrhythmia; however, the underlying mechanism has not been elucidated. Methods: In this study, we randomly categorized 22 adult mongrel dogs into a control group, MNS group 1, and MNS group 2. After a 4-week experimental myocardial infarction (MI), ventricular electrophysiology was measured in the MNS group 1 before and after 30 min of MNS. The same measurements were performed in the MNS group 2 dogs via bilateral vagotomy. Venous blood and ventricular tissue were collected to detect molecular indicators related to inflammation and cholinergic pathways by enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), and Western blot (WB). Results: No significant changes were reported in the ventricular effective refractory period (ERP) in the MNS group 1 and MNS group 2 dogs before and after MNS. The ventricular fibrillation threshold (VFT) in the MNS group 1 was significantly higher than that in the MNS group 2 (20.3 ± 3.7 V vs. 8.7 ± 2.9 V, P < 0.01). The levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and nuclear transcription factor-κB (NF-κB) were lower (P < 0.01), whereas the levels of Ach were higher in the peri-infarct zone tissues in the MNS group 1 dogs than those in the MNS group 2 dogs (P < 0.01). Conclusion: This study demonstrated that MNS increases VFT in a canine model with MI. The effects of MNS on VFT are potentially associated with the cholinergic anti-inflammatory pathway.

The Transient Receptor Potential Vanilloid 2 (TRPV2) Channel Facilitates Virus Infection Through the Ca2+ -LRMDA Axis in Myeloid Cells.

The transient receptor potential vanilloid 2 (TRPV2) channel is a nonselective cation channel that has been implicated in multiple sensory processes in the nervous system. Here, it is shown that TRPV2 in myeloid cells facilitates virus penetration by promoting the tension and mobility of cell membrane through the Ca2+ -LRMDA axis. Knockout of TRPV2 in myeloid cells or inhibition of TRPV2 channel activity suppresses viral infection and protects mice from herpes simplex virus 1 (HSV-1) and vesicular stomatitis virus (VSV) infection. Reconstitution of TRPV2 but not the Ca2+ -impermeable mutant TRPV2E572Q into LyZ2-Cre;Trpv2fl/fl bone marrow-derived dendritic cells (BMDCs) restores viral infection. Mechanistically, knockout of TRPV2 in myeloid cells inhibits the tension and mobility of cell membrane and the penetration of viruses, which is restored by reconstitution of TRPV2 but not TRPV2E572Q . In addition, knockout of TRPV2 leads to downregulation of Lrmda in BMDCs and BMDMs, and knockdown of Lrmda significantly downregulates the mobility and tension of cell membrane and inhibits viral infections in Trpv2fl/fl but not LyZ2-Cre;Trpv2fl/fl BMDCs. Consistently, complement of LRMDA into LyZ2-Cre;Trpv2fl/fl BMDCs partially restores the tension and mobility of cell membrane and promotes viral penetration and infection. These findings characterize a previously unknown function of myeloid TRPV2 in facilitating viral infection though the Ca2+ -LRMDA axis.

Identification of a Cancer Stem Cells Signature of Head and Neck Squamous Cell Carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) ranks as the sixth most widespread and deadly cancer. In recent times, it has been determined that undifferentiated cell populations with stem cell-like properties in HNSCC are major factors influencing recurrence and progression. Method: In this study, we determine key genes related to stemness by merging WGCNA with HNSCC mRNAsi based on the online database. Results: We first download the mRNA expression-based stemness index (mRNAsi) data and contrast the expression levels of mRNAsi in cancers and control samples; we found significantly elevated mRNAsi expressions in HNSCC tissues (p = 0.002). Moreover, the brown module showed a relatively high negative correlation with mRNAsi (cor = -0.8). Thus, we selected the brown module as the interesting module and used it for following analysis. We screened 20 key genes (PDGFRB, PLPP4, CALU, ADAMTS14, COL5A3, KCNE4, LOXL1, CLEC11A, PODN,BGN, AEBP1, COL1A2, LAMA4, LOXL2, LRRC15, THY1, SPON2, COL1A1, NID2, and AC134312.5) including and as to decide the neighbor genes biological interaction network of these 20 stemness-related genes in HNSCC. The top 10 frequent alterations were PIK3CA, FGF3, FGF19, FGF4, DVL3, P3H2, GNB4, COL22A1, COL14A1, and PLOD2. Conclusion: This study showed the critical role of stemness-related genes in HNSCC. However, more related studies are needed to confirm these results.

Pyroptosis-Related Signature and Tumor Microenvironment Infiltration Characterization in Head and Neck Squamous Cell Carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most widespread and deadly cancer. Until now, very few studies have systematically evaluated the role of pyroptosis-related genes (PRGs) and lncRNAs in HNSCC patients. Methods: We integrated the genomic data to comprehensively assess the role of pyroptosis with the tumor microenvironment cell-infiltrating characteristics in HNSCC. In addition, we also constructed a set of the scoring system to calculate the pyroptosis dysfunction in each patient. Results: The analysis of the CNV alteration frequency displayed that CNV changes were common in 33 PRGs, and the frequency of copy number gain and loss was similar. CASP8 demonstrated the highest mutation frequency. Considering the individual heterogeneity, a scoring system to quantify the pyroptosis pattern in each patient was constructed based on these phenotypic-related genes, which we named as the PyroptosisScore. The results indicated that the low PyroptosisScore group experienced increased extensive TMB than the high group, with the most significant mutated genes being TP53 and TTN. Finally, we tried to find some useful pyroptosis-related lncRNAs, and 14 differentially expressed lncRNAs were selected as independent prognosis factors of HNSCC patients based on the multivariate Cox analysis. Conclusion: This work suggests the pyroptosis features and the potential mechanisms of the tumor microenvironment. The exploration may assist in identifying novel biomarkers and help patients predict prognosis, clinical diagnosis, and management.

Bioinformatics Study Revealed Significance of Exosome Transcriptome in Hepatocellular Carcinoma Diagnosis.

Background: Hepatocellular carcinoma (HCC) is one of the fifty most common cancers globally, having a high mortality rate being the second most common cause of cancer-related deaths. However, little attention has been paid to the involvement of exosomes and ceRNA in HCC. Method: The study aimed to explore exosome data from exoRBase database and a free online database to estimate possible binding miRNA from mRNA, lncRNA, and circRNA and discover useful exosome biomarkers for HCC therapy. Results: The results indicated that a total of 159 mRNAs, 60 lncRNAs, and 13 circRNAs were differentially expressed, with HIST2H3C exhibiting the highest log2FC change, CTD-2031P19 exhibiting the most relevant lncRNA, and CTD-2031P19 exhibiting the most relevant lncRNA. MARCH8, SH3PXD2A, has-circ-0014088, hsa-miR-186-5p, and hsa-miR-613 were identified as hub biomarkers used by Cytoscape. According to the KEGG pathway analysis results, the differentially expressed proteins were primarily enriched in the MAPK signaling network, central carbon metabolism in cancer, the glucagon signaling pathway, glutamatergic synapse, and spliceosome. Furthermore, immunohistochemical images from the Human Protein Atlas (HPA) online tool were used to directly evaluate the protein expression of SMARCA5, CDC42, and UBC between normal and cancer tissues, and the results showed that these three gene expressions were significantly higher in tumor tissues. Conclusion: This study discovered atypical signature exosomes for HCC prognostic prediction based on an online database. The signals could mimic exosome microenvironmental disorders providing potential biomarkers for exosome treatment.

Identification of an arthropod molecular target for plant-derived natural repellents.

Arthropods maintain ecosystem balance while also contributing to the spread of disease. Plant-derived natural repellents represent an ecological method of pest control, but their direct molecular targets in arthropods remain to be further elucidated. Occupying a critical phylogenetic niche in arthropod evolution, scorpions retain an ancestral genetic profile. Here, using a behavior-guided screening of the Mesobuthus martensii genome, we identified a scorpion transient receptor potential (sTRP1) channel that senses Cymbopogon-derived natural repellents, while remaining insensitive to the synthetic chemical pesticide DEET. Scrutinizing orthologs of sTRP1 in Drosophila melanogaster, we further demonstrated dTRPγ ion channel as a chemosensory receptor of natural repellents to mediate avoidance behavior. This study sheds light on arthropod molecular targets of natural repellents, exemplifying the arthropod­plant adaptation. It should also help the rational design of insect control strategy and in conserving biodiversity.

DNA methylation molecular subtypes for prognosis prediction in lung adenocarcinoma.

AIMS: Lung cancer is one of the main results in tumor-related mortality. Methylation differences reflect critical biological features of the etiology of LUAD and affect prognosis. METHODS: In the present study, we constructed a prediction prognostic model integrating various DNA methylation used high-throughput omics data for improved prognostic evaluation. RESULTS: Overall 21,120 methylation sites were identified in the training dataset. Overall, 237 promoter genes were identified by genomic annotation of 205 CpG loci. We used Akakike Information Criteria (AIC) to obtain the validity of data fitting, but to prevent overfitting. After AIC clustering, specific methylation sites of cg19224164 and cg22085335 were left. Prognostic analysis showed a significant difference among the two groups (P = 0.017). In particular, the hypermethylated group had a poor prognosis, suggesting that these methylation sites may be a marker of prognosis. CONCLUSION: The model might help in the identification of unknown biomarkers in predicting patient prognosis in LUAD.

The industrial solvent 1,4-dioxane causes hyperalgesia by targeting capsaicin receptor TRPV1.

BACKGROUND: The synthetic chemical 1,4-dioxane is used as industrial solvent, food, and care product additive. 1,4-Dioxane has been noted to influence the nervous system in long-term animal experiments and in humans, but the molecular mechanisms underlying its effects on animals were not previously known. RESULTS: Here, we report that 1,4-dioxane potentiates the capsaicin-sensitive transient receptor potential (TRP) channel TRPV1, thereby causing hyperalgesia in mouse model. This effect was abolished by CRISPR/Cas9-mediated genetic deletion of TRPV1 in sensory neurons, but enhanced under inflammatory conditions. 1,4-Dioxane lowered the temperature threshold for TRPV1 thermal activation and potentiated the channel sensitivity to agonistic stimuli. 1,3-dioxane and tetrahydrofuran which are structurally related to 1,4-dioxane also potentiated TRPV1 activation. The residue M572 in the S4-S5 linker region of TRPV1 was found to be crucial for direct activation of the channel by 1,4-dioxane and its analogs. A single residue mutation M572V abrogated the 1,4-dioxane-evoked currents while largely preserving the capsaicin responses. Our results further demonstrate that this residue exerts a gating effect through hydrophobic interactions and support the existence of discrete domains for multimodal gating of TRPV1 channel. CONCLUSIONS: Our results suggest TRPV1 is a co-receptor for 1,4-dioxane and that this accounts for its ability to dysregulate body nociceptive sensation.

The Role of α7nAChR-Mediated Cholinergic Anti-Inflammatory Pathway in Vagal Nerve Regulated Atrial Fibrillation.

The aim was to investigate the role of the α7nAChR-mediated cholinergic anti-inflammatory pathway in vagal nerve regulated atrial fibrillation (AF).18 beagles (standard dogs for testing) were used in this study, and the effective refractory period (ERP) of atrium and pulmonary veins and AF inducibility were measured hourly during rapid atrial pacing at 800 beats/minute for 6 hours in all beagles. After cessation of 3 hours of RAP, the low-level vagal nerve stimulation (LL-VNS) group (n = 6) was given LL-VNS and injection of salinne (0.5 mL/GP) into four GPs, the methyllycaconitine (MLA, the antagonist of α7nAChR) group (n = 6) was given LL-VNS and injection of MLA into four GPs, and the Control group (n = 6) was given saline into four GPs and the right cervical vagal nerve was exposed without stimulation. Then, the levels of the tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), acetylcholine (ACh), STAT3, and NF-κB proteins were measured. During the first 3 hours of RAP, the ERPs gradually decreased while the dispersion of ERPs (dERPs) and AF inducibility gradually increased in all three groups. During the last 3 hours of 6 hours' RAP in this study, the ERPs in the LL-VNS group were higher, while the dERPs and AF inducibility were significantly lower when compared with the Control and MLA groups at the same time points. The levels of ACh in the serum and atrium in the LL-VNS and MLA groups were higher than in the Control group, and the levels of TNF-α and IL-6 were higher in the Control and MLA groups than in the LL-VNS group. The concentrations of STAT3 in RA and LA tissues were higher in the LL-VNS group while those of NF-κB were lower.In conclusion, the cholinergic anti-inflammatory pathway mediated by α7nACh plays an important role in low-level vagal nerve-regulated AF.

Ferroptosis-Related Long Non-Coding RNA signature predicts the prognosis of Head and neck squamous cell carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) are head and neck cancers. On the other hand, ferroptosis is a novel iron-dependent and ROS reliant type of cell death observed various disease conditions. Method: We constructed a prognostic multilncRNA signature based on ferroptosis-related differentially expressed lncRNAs in HNSCC. Results: We identified 25 differently expressed lncRNAs associated with prognosis of HNSCC. Kaplan-Meier analyses revealed the high-risk lncRNAs signature associated with poor prognosis of HNSCC. Moreover, the AUC of the lncRNAs signature was 0.782, underscoring their utility in prediction HNSCC prognosis. Indeed, our risk assessment model was superior to traditional clinicopathological features in predicting HNSCC prognosis. GSEA revealed the immune and tumor-related pathways in the low risk group individuals. Moreover, TCGA revealed T cell functions including cytolytic activity, HLA, regulation of inflammationp, co-stimulation, co-inhibition and coordination of type II INF response were significantly different between the low-risk and high-risk groups. Immune checkpoints such as PDCD-1 (PD-1), CTLA4 and LAG3, were also expressed differently between the two risk groups. Conclusion: A novel ferroptosis-related lncRNAs signature impacts on the prognosis of HNSCC.

Flotillin-1 Interacts With and Sustains the Surface Levels of TRPV2 Channel.

Transient receptor potential vanilloid subtype 2 (TRPV2) channel is a polymodal receptor regulating neuronal development, cardiac function, immunity and oncogenesis. The activity of TRPV2 is regulated by the molecular interactions in the subplasmalemmel signaling complex. Here by yeast two-hybrid screening of a cDNA library of mouse dorsal root ganglia (DRG) and patch clamp electrophysiology, we identified that flotillin-1, the lipid raft-associated protein, interacts with TRPV2 channel and regulates its function. The interaction between TRPV2 and flotillin-1 was validated through co-immuoprecipitation in situ using endogenous DRG neurons and the recombinant expression model in HEK 293T cells. Fluorescent imaging and bimolecular fluorescence complementation (BiFC) further revealed that flotillin-1 and TRPV2 formed a functional complex on the cell membrane. The presence of flotillin-1 enhanced the whole-cell current density of TRPV2 via increasing its surface expression levels. Using site-specific mapping, we also uncovered that the SPFH (stomatin, prohibitin, flotillin, and HflK/C) domain of flotillin-1 interacted with TRPV2 N-termini and transmembrane domains 1-4, respectively. Our findings therefore demonstrate that flotillin-1 is a key element in TRPV2 signaling complex and modulates its cellular response.

Cancer Stem Cell Characteristics by Network Analysis of Transcriptome Data Stemness Indices in Breast Carcinoma.

OBJECTIVE: Breast cancer (BC) affects women all over the world. This study aimed at screening out potential biomarkers through performing an in-depth analysis of data from the previous research and database. DESIGN: This study made full use of RNA sequencing (RNA-seq) data from cancer genomic maps (TCGA) and screened key genes related to stemness by merging WGCNA with BC mRNAsi. RESULTS: The related mRNAsi data were downloaded, and the transcriptional levels of mRNAsi in cancers contrasted with normal samples. The results showed that there was a significantly higher mRNAsi expression in BC tissues (P=1.791e - 43). Seven modules were obtained following the investigation through cluster analysis. The turquoise module showed a relatively high positive correlation with mRNAsi at 0.79; this module was chosen as the most interesting and was used for subsequent analysis. By setting related cutoffs, 38 key genes were screened, and the coexpression of these genes was explored next. The results showed that the lowest correlation was between CDC20 and KIF11 (0.54), and the highest connection was between BUB1 and CKAP2L (0.86). Furthermore, ten hub genes with the most nodes were sorted using a histogram. Using other databases to explore the prognosis value of key genes, the results showed that lower expression of key genes was significantly connected with longer overall survival (OS), distant metastasis-free survival (DMFS), and relapse-free survival (RFS). The immune infiltration relationship between hub genes and six kinds of basic immune cells was investigated; it was revealed that partial ones were positively or negatively related. CONCLUSION: This study is the first to show the important role of stemness-related genes in the prognosis of BC. However, future clinical trials are needed to confirm these results and promote the application of these key genes in prognosis evaluation.

Comprehensive Analysis of the Expression and Prognosis for SFRPs in Breast Carcinoma.

Secreted frizzled-related proteins (SFRPs) are a group of five secreted glycoproteins-SFRP1, SFRP2, SFRP3 (frizzled related protein, FRZB), SFRP4, and SFRP5-which contain a frizzled-related cysteine-rich domain and a netrin module. We analyzed SFRPs' expression levels, mutations, regulation, functional networks, and correlation with immune infiltration in breast cancer (BC) patients using data from multiple open databases. SFRP1/3/4/5 were downregulated and SFRP2 was upregulated in BC patients compared to healthy controls. Furthermore, higher levels of SFRP1/3/4 were significantly associated with favorable prognosis. In addition, the prognostic significance of the infiltrating B cells was correlated to the SFRPs. Based on these findings, we hypothesize that SFRPs play a synergistic role in BC progression, and are, therefore, promising prognostic biomarkers as well as therapeutic targets.

High GJB2 mRNA expression and its prognostic significance in lung adenocarcinoma: a study based on the TCGA database.

Lung adenocarcinoma (LUAD), a form of lung cancer, is reported to cause first and second-order cancer morbidity to men and women in China, respectively. We assessed the mRNA expression of GJB2 in LUAD patients in our study, based on data acquired from the cancer genome atlas (TCGA) and so as to increase further knowledge into the biological pathways involved in LUAD pathogenesis related to GJB2.Information on gene expression and comparing clinical data were recognized and downloaded from TCGA. Gene set enrichment analysis (GSEA) created an arranged list of all genes is indicated by their connection with GJB2 expression.Our study cohort included 265 (54.5%) female and 221 (36.0%) male patients. The scatter plot and paired plot showed the difference of GJB2 expression between normal and tumor samples (P < .01). Overall survival (OS) analysis demonstrated that LUAD with GJB2 -high had a more terrible prognosis than that with GJB2 -low (P < .01). Multivariate analysis with the cox proportional hazards model indicated that the expression of Cx26 (HR: 1.00; 95%CI: 1.00-1.01; P = .041) and stage (HR: 1.95; 95%CI: 1.23-3.09; P = .003) were independent prognostic factors for patients with LUAD. The GSEA results showed that cytosolic DNA sensing pathway, apoptosis, cytokine-cytokine receptor interaction, natural killer cell mediated cytotoxicity, regulation of actin cytoskeleton, toll-like receptor signaling pathway, small cell lung cancer and pathways in cancer are differentially enriched in GJB2 high expression phenotype.Our study confirmed the significantly high levels of Cx26 expression in LUAD patients with several observed clinical features. GJB2 may be a potentially useful prognostic molecular biomarker of bad survival in LUAD, while further experimental ought to be performed to demonstrate the biologic effect of GJB2.

High ubiquitin conjugating enzyme E2 T mRNA expression and its prognostic significance in lung adenocarcinoma: A study based on the TCGA database.

Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer with a high mortality disease which has been positioned the first and second cancer morbidity of men and women in China, separately. Our study was to assess the prognostic meaningful of ubiquitin conjugating enzyme E2 T (UBE2T) expression in LUAD dependent on data acquired from The Cancer Genome Atlas (TCGA) and so as to increase further knowledge into the biological pathways involved in LUAD pathogenesis related to UBE2T.Information on gene expression and comparing clinical data were recognized and downloaded from TCGA. Gene set enrichment analysis (GSEA) created an arranged list of all genes s indicated by their connection with UBE2T expression.Our study cohort included 265 (54.5%) female and 221 (36.0%) male patients. The scatter plot and paired plot showed the difference of UBE2T expression between normal and tumor samples (P < .01). Overall survival (OS) analysis demonstrated that LUAD with UBE2T-high had a more terrible prognosis than that with UBE2T-low (P < .01). Multivariate analysis with the cox proportional hazards model indicated that the expression of UBE2T (hazard ratio [HR]: 1.28; 95% Confidence Interval (CI): 1.06-1.56; P = .011) and stage (HR: 2.02; 95% CI: 1.27-3.21; P = .003) were independent prognostic factors for patients with LUAD. The GSEA results showed that cell cycle, DNA replication, RNA degradation, oxidative phosphorylation, pathogenic Escherichia coli infection, citrate cycle tricarboxylic acid cycle, Alzheimer's disease, P53 signaling pathway, and purine metabolism are differentially enriched in UBE2T high expression phenotype.Our study found that the expression of UBE2T was significantly increased in LUAD patients and associated with several clinical features. UBE2T may be a potentially useful prognostic molecular biomarker of bad survival in LUAD, while further experimental ought to be performed to demonstrate the biologic effect of UBE2T.