The global incidence of thyroid cancer is rising, yet its underlying molecular etiology remains elusive. This study aimed to investigate the roles of transcription factor ATF3 and miR-27b-3p in thyroid cancer. Bioinformatics analysis identified miR-27b-3p as the upstream regulatory miRNA of ATF3. In thyroid cancer, ATF3 was found to be downregulated, whereas miR-27b-3p was upregulated, and both were associated with aggressive tumor features. Their expression in clinical thyroid cancer samples was measured via qRT-PCR and immunohistochemistry (IHC), which confirmed decreased ATF3 expression and increased miR-27b-3p levels. Higher miR-27b-3p expression was associated with C-TIRADS classification, TNM stage, and serum TSH levels. A dual-luciferase reporter assay confirmed that miR-27b-3p directly targets ATF3, and inhibiting miR-27b-3p markedly increased ATF3 expression. Additionally, functional experiments demonstrated that overexpressing miR-27b-3p or knocking down ATF3 enhanced thyroid cancer cell proliferation, migration, and invasion. Conversely, inhibiting miR-27b-3p or overexpressing ATF3 suppressed these malignant phenotypes, while simultaneous silencing of miR-27b-3p and ATF3 partially rescued the inhibitory effects. These findings suggest that miR-27b-3p enhances thyroid cancer cell aggressiveness in part by inhibiting ATF3, providing insights that warrant further investigation.

BACKGROUND:MRI is the preferred imaging modality for staging of confirmed nasopharyngeal carcinoma (NPC) per the 8th UICC/AJCC system, but its diagnostic performance in patients with suspected NPC remains unclear. OBJECTIVES:To evaluate the clinical value of MRI combined with peripheral blood EBV detection in the diagnosis of NPC. METHODS:This retrospective analysis enrolled patients with suspected NPC from a tertiary hospital between September 2022 and June 2023. Using histopathology as the reference standard, we evaluated the diagnostic performance (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC)) of nasopharyngeal MRI and EBV serology. Receiver operating characteristic (ROC) curve analysis was performed to calculate AUCs and optimal thresholds. Cases involving discordance between pathological and MRI diagnoses were further evaluated. RESULTS:The combined application of MRI and peripheral blood EBV testing demonstrated excellent diagnostic performance for the diagnosis of NPC (AUC: 0.979). The novel integrated MRI-EBV testing strategy mitigates the inflammation-related diagnostic limitations of unimodal testing for NPC, preventing misdiagnosis, improving lymphoma differentiation and reducing pathological missed diagnoses. CONCLUSIONS:MRI and EBV testing are highly valuable for NPC screening, and their combined application shows superior diagnostic efficacy and clinical utility, pending prospective multi-center validation.

Background:Bladder cancer (BCa) is characterized by substantial molecular and clinical heterogeneity, hindering accurate prognostic assessment and treatment stratification. This study aimed to develop a machine learning-based prognostic model based on DNA repair-related genes and to investigate the functional relevance of representative genes in BCa. Methods:To address this, we constructed a DNA repair-related risk score (DRRS) using 101 machine learning algorithms based on transcriptomic profiles from BCa cohorts. The prognostic value, immune relevance, and therapeutic implications of DRRS were systematically evaluated. ZW10 interacting kinetochore protein (ZWINT), selected as a representative gene within the DRRS, was subjected to functional characterization through in vitro experiments. Results:DRRS effectively stratified BCa patients into high- and low-risk groups with distinct survival outcomes, immune microenvironment features, and associations with responses to chemotherapy and immunotherapy. Functional assays revealed that ZWINT knockdown suppressed cell proliferation, migration, and invasion, induced apoptosis, and caused G1 phase cell cycle arrest. Transcriptomic analysis and Western blot validation demonstrated increased phosphorylation of p65 following ZWINT knockdown, indicating activation of the NF-κB signaling pathway, potentially as part of a feedback mechanism associated with apoptosis. Conclusions:This study establishes a machine learning-based DNA repair signature for BCa and functionally validates ZWINT as a potential oncogenic driver. The findings provide new insight into BCa progression and highlight DRRS and ZWINT as promising biomarkers and therapeutic targets for treatment stratification.

Background:Bladder urothelial carcinoma (BLCA) is a prevalent malignancy with high recurrence rates and limited therapeutic options, necessitating the identification of novel biomarkers for precision medicine. This study investigates the expression and clinical significance of multivesicular body subunit 12B (MVB12B) in BLCA, aiming to evaluate its potential as a prognostic biomarker and therapeutic target. Methods:We systematically evaluated MVB12B expression across 33 cancer types from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets, and the expression of MVB12B in BLCA was verified using the GSE3167 dataset. Next, the expression of MVB12B in BLCA patients with different clinicopathologic features was analyzed. Then, survival analysis was conducted through the Encyclopedia of RNA Interactomes (ENCORI) database. The receiver operating characteristic (ROC) curves were conducted to assess the diagnostic values of MVB12B. Furthermore, the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was used to construct a protein-protein interaction (PPI) network, and gene set enrichment analysis (GSEA) was performed to explore potential pathways through which MVB12B might influence BLCA. Finally, immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR) and cellular experiments were used to investigate the role of MVB12B in BLCA. Results:Our study reported that MVB12B was significantly downregulated in 14 cancer types, particularly in BLCA, in which low expression correlated with advanced tumor stage (III & IV), histological grade (high), and worse overall survival in BLCA patients. PPI networks identified MVB12B's interactions with endosomal sorting complex required for transport (ESCRT) components, and GSEA revealed that MVB12B was significantly involved in keratinization and intermediate filament organization. Experimental validation in clinical samples and BLCA cell lines (T24, UM-UC-3) revealed that MVB12B expression was reduced in tumor tissues and BLCA cell lines. Functional assays demonstrated that MVB12B overexpression suppressed BLCA cell proliferation and migration in vitro, indicating its tumor-suppressive role. Conclusions:MVB12B functions as a tumor-suppressive role in BLCA and is associated with good prognosis in BLCA patients. MVB12B can be used as a potential biomarker for prognosis and therapeutic of BLCA.

Hemoglobin H Disease-Constant Spring (HbH-CS) represents a severe variant of α-thalassemia characterized by a fundamental pathological mechanism involving inadequate synthesis of α-globin chains. This deficiency results in the formation of unstable Hemoglobin H (HbH) due to the aggregation of free β-globin chains, which subsequently induces an imbalance in oxidative stress within erythrocytes. This imbalance leads to an abnormal accumulation of reactive oxygen species (ROS), which in turn promotes lipid peroxidation, culminating in the production of malondialdehyde (MDA) and a significant depletion of glutathione (GSH). Concurrently, Nrf2 is translocated to the nucleus, where it activates the antioxidant response element (ARE) to mitigate cellular stress. Here, we report that NSUN3 (which, together with ALKBH1, maintains mitochondrial function through m5C→f5C modification) is abnormally overexpressed in reticulocytes from patients with HbH-CS, and an in vitro cellular model of NSUN3 overexpression/silencing was constructed using K562 cells, which have the potential for erythroid lineage differentiation and retain an intact cluster of bead protein genes. Functional assays indicated that the overexpression of NSUN3 significantly intensified the accumulation of intracellular ROS and MDA, led to a reduction in GSH levels, and diminished the overall cellular antioxidant capacity (T-AOC). This may be due to ROS accumulation resulting from inhibition of mitochondrial respiratory chain complex I, II, and IV synthesis through aberrant m5C→f5C modification. In addition, NSUN3 overexpression further exacerbates oxidative stress by inhibiting the phosphorylation of Nrf2 hindering its translocation into the nucleus and weakening the cellular antioxidant system. Moreover, we also observed that NSUN3 overexpression exacerbated intracellular DNA damage and inhibited cellular value-added activity, and silencing NSUN3 showed the opposite result. Our research offers initial insights into the molecular mechanisms through which NSUN3 modulates oxidative stress in erythrocytes via its role in epigenetic modifications. These findings contribute to a deeper understanding of the clinical management of patients with Hb H-CS.

ETHNOPHARMACOLOGICAL RELEVANCE:Rosa roxburghii is an ethnic medicinal herb. Folk medicine collections have documented its nourishing and strengthen effects. It has been used to improve reproductive health, but scientific evidence supporting its efficacy and mechanisms remains limited. AIM OF THIS STUDY:Endocrine-disrupting chemicals, such as di-(2-ethylhexyl) phthalate (DEHP), are known to impair male reproductive health. This study aims to investigate the protective effects of raw Rosa roxburghii juice (RRJ) on DEHP-induced reproductive toxicity in mice and elucidates its underlying mechanisms. MATERIALS AND METHODS:Using a DEHP-induced murine model of reproductive damage, we evaluated the effects of RRJ on sperm quality, testicular histopathology, reproductive endocrine function, oxidative stress, inflammation, apoptosis, and DNA damage. Network pharmacology analysis was performed to identify the active components, targets, and mechanisms underlying the therapeutic effects of Rosa Roxburghii. RESULTS:Our data demonstrated that RRJ significantly improved sperm quality, alleviated testicular atrophy, restored endocrine disorders, and mitigated oxidative stress, inflammation, and apoptosis in testicular tissues. Additionally, RRJ reduced testicular and sperm DNA damage, as evidenced by decreased γ-H2AX expression and DNA fragmentation index. Network pharmacology analysis identified quercetin, apigenin, luteolin, kaempferol, eriodictyol, and ellagic acid as the key bioactive compounds in RRJ, with the PI3K/AKT signaling pathway playing a crucial role in its therapeutic effects. Western blotting confirmed that RRJ reversed DEHP-induced suppression of the PI3K/AKT pathway. CONCLUSIONS:This study demonstrates that RRJ protects against DEHP-induced reproductive toxicity through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms, mediated in part by the PI3K/AKT signaling pathway. This work provides the first comprehensive evidence of the protective effects of Rosa roxburghii against male reproductive system damage and its underlying mechanisms.

NSUN3 (NOP2/Sun RNA methyltransferase family member 3) is a gene encoding an RNA methyltransferase primarily responsible for specific methylation modifications on mitochondrial tRNA. Recent studies have indicated that aberrant expression of NSUN3 may be associated with the development of a range of tumors. UALCAN and GEPIA2 were utilized for bioinformatics analyses, while lentiviral vectors and small interfering RNA techniques were employed to create cell lines with either overexpression or silencing of NSUN3. To assess the impact of NSUN3 on hepatocellular carcinoma cells in vitro, CCK-8 assays, apoptosis assays, and cell cycle analyses were conducted. The accumulation of ROS mediated by NSUN3 was evaluated using fluorescent probes specific for ROS. Additionally, Western blotting was performed to verify transfection efficiency and to analyze the expression levels of the PI3K/AKT signaling pathway and BCL-2 protein. The findings of the current investigation indicate that NSUN3 is markedly overexpressed in HCC and is associated with a negative prognosis. The role of NSUN3 in modulating mitochondrial energy metabolism implies that its overexpression may facilitate the proliferation of HCC cells through the promotion of ROS accumulation. In contrast, the silencing of NSUN3 has been demonstrated to hinder the proliferation of HCC cells. Furthermore, the results also indicate that NSUN3 has the capacity to activate the PI3K/AKT signaling pathway, this resulted in the preliminary clarification of the molecular mechanisms at play. In summary, our research addresses the functional role of NSUN3 in HCC. The initial identification of NSUN3 suggests that it may serve as a promising target for the development of novel therapeutic strategies in the treatment of HCC.

Liver hepatocellular carcinoma (LIHC) represents a category of malignant neoplasms that present a considerable risk to public health. Recent studies have increasingly focused on the biological roles of messenger RNAs (mRNAs) linked to deubiquitinating enzymes in the context of LIHC. These deubiquitinating enzyme-associated mRNAs have been utilized to construct a prognostic model for this type of cancer. Prognostic mRNAs associated with LIHC were identified through univariate Cox regression and co-expression analysis. A clinical risk prediction model was established utilizing multivariate Cox regression and least absolute shrinkage and selection operator analysis, resulting in the stratification of patients into high-risk and low-risk categories. The model's accuracy and clinical significance were assessed through various methodologies, including receiver operating characteristic curves, area under the curve calculations, univariate and multivariate Cox regression analyses, principal component analysis, t-distributed stochastic neighbor embedding, Kaplan-Meier Plotter, gene set enrichment analysis, tumor mutation burden analysis, immune infiltration analysis, and drug sensitivity prediction. The UALCAN database was employed to validate the aberrant expression of the identified characteristic genes, and consistency clustering analysis was conducted to delineate and compare the molecular subtypes of LIHC. The risk model we developed exhibited robust predictive capabilities, with the high-risk cohort demonstrating reduced survival rates across various clinical contexts. This group also presented a more pronounced tumor mutation burden, exhibited stronger correlations with immune cell populations, and displayed heightened activation of numerous immune checkpoints. Notably, the characteristic genes (CBX2, ERGIC3, GNL2) were found to be aberrantly overexpressed in the cancer genome atlas cohort, correlating with unfavorable prognostic outcomes, and may play a role in tumor invasion and metastasis. Consistency clustering analysis revealed 3 distinct subtypes (C1, C2, C3), with subtype C3 showing elevated activation levels at the majority of immune checkpoints in comparison to subtypes C2 and C1, as well as increased sensitivity to pharmacological agents such as 5-fluorouracil and afatinib. The prognostic assessment model developed in this research offers an innovative approach for the identification of novel prognostic markers in patients diagnosed with (LIHC).

Background: ATAD2, a member of the AAA + ATPase family and a known cancer/testicular antigen, has demonstrated oncogenic properties in various cancers. Despite its established role in cancer progression, a comprehensive pan-cancer analysis of its prognostic significance, therapeutic predictive potential, and immunological associations has not been conducted. Methods: We performed a pan-cancer analysis of ATAD2 using data from The Cancer Genome Atlas (TCGA), assessing its expression profiles across different tumor types. We examined its correlations with survival prognosis, clinical outcomes, and cancer-associated signaling pathways. Additionally, we explored the relationship between ATAD2 expression and the tumor immune microenvironment, as well as its predictive value for responses to immunotherapy, targeted therapy, and chemotherapy. Results: ATAD2 was significantly upregulated in multiple tumor types, and its increased expression was associated with poor prognosis and adverse clinical outcomes. Further analysis revealed that ATAD2 expression was closely linked to cancer-related signaling pathways, tumor mutational burden, and microsatellite instability. Moreover, ATAD2 expression showed strong correlations with immune cell infiltration, immune-related gene expression, and responses to various treatment regimens, including immunotherapy, targeted therapy, and chemotherapy. Conclusion: ATAD2 is a critical biomarker for poor prognosis and treatment response across a wide range of cancers. Its ability to predict therapeutic responses, particularly for immunotherapy, targeted therapy, and chemotherapy, underscores its clinical significance. Further experimental studies and clinical trials are needed to explore ATAD2’s role in cancer progression and its involvement in therapeutic resistance mechanisms.

Background: Hemoglobin (Hb) Hekinan II (A27; Glu-Asp) is an alpha-chain variant, and its interaction with the common Southeast Asian (--(SEA)/) alpha-thalassemia (alpha-thal) deletion is rarely reported. This study provides a clinical update of Hb Hekinan II associated with (--(SEA)/) alpha-thal. Methods: A total of 11 simple heterozygotes and 20 composite heterozygotes for Hb Hekinan II and (--(SEA)/) alpha-thal were included based on molecular diagnosis. Results: Hb Hekinan II exhibited a significant increase in hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin content, but a decrease in red blood cell level compared with alpha(+) thalassemia deletion. Compared with (--(SEA)/) alpha-thal, composite heterozygotes for Hb Hekinan II and (--(SEA)/) alpha-thal showed similar erythrocyte parameters. Both heterozygotes with and without (--(SEA)/) alpha-thal showed low Hb A(2) level. Hb Hekinan II showed abnormal performance in high-performance liquid chromatography but not in capillary electrophoresis. Conclusion: Hb Hekinan II is a benign Hb variant. The heterozygotes exhibit clinically asymptomatic coinheritance with (--(SEA)/) alpha-thal having comparable hematological phenotype to simple (--(SEA)/) alpha-thal. The combination of hematological and molecular analysis helped to improve the detection rate of this rare variant.

Bladder carcinoma (BLCA) represents a common urinary tract malignancy, characterized by aggressive behavior and high recurrence rates. The biological response regulation during tumor proliferation and metastasis is intimately associated with liquid-liquid phase separation (LLPS). For the purpose of enhancing early detection and treatment, this study employed transcriptomic data to examine the prognostic implications of LLPS-associated genes and formulate a predictive model. Clinical and transcriptomic data of bladder cancer patients were sourced from the GEO and TCGA databases. This study applied a clustering algorithm using non-negative matrix factorization (NMF) to classify samples, which were systematically compared based on their liquid-liquid phase separation characteristics. Prognostic models were developed using multivariate Cox regression and the Least Absolute Shrinkage Selection Operator (LASSO) algorithm to establish risk formulas for nine genes. The gene signature’s validity was tested across the entire TCGA cohort (406 cases), the TCGA testing cohort (120 cases), and the external validation dataset GSE13507. The predictive accuracy of the signature system was assessed using receiver operating characteristic (ROC) and Kaplan-Meier curves. Additionally, decision curve analysis incorporating clinicopathological parameters and the genetic signature was employed to predict individual survival. This study identified two distinct molecular subtypes, C1 and C2. Patients with the C1 subtype exhibited significantly better prognoses than those with the C2 subtype. Low-risk group patients consistently showed superior prognoses compared to high-risk groups across the entire TCGA, GEO, and TCGA training cohorts. Furthermore, the LLPS-related gene model demonstrated prognostic value independent of other clinical traits. This study identifies LLPS-associated gene clusters and establishes an independent, accurate prognostic model for BLCA. The model holds potential for clinical application in BLCA prognosis assessment.

Chronic lymphocytic leukemia (CLL) is a highly heterogeneous disease. Despite recent tremen-dous progress in managing CLL, the disease remains incurable with clinical therapies, and relapse is inevitable. To overcome this, new diagnostic and prognostic markers need to be investigated. We thus screened through the public database for genes with diagnostic, prognostic, and therapeutic implications in CLL. We further performed RT-qPCR and Western blot analysis to measure the candidate gene and protein expression levels, respectively, in peripheral blood mononuclear cells. Our results indicated that Glyoxalase 1 (GLO1) expression was significantly higher in patients with CLL than in healthy controls. Furthermore, cell proliferation, apoptosis, and cell cycle assay results together indicated that S-p-bromobenzylglutathione cyclopentyl diester (BBGC), an effective inhibitor of GLO1, suppresses the progression of CLL. Bioinformatics analysis revealed that GLO1 expression is closely associated with CDK4 expression in a wide variety of cancer types, and inhibition of CDK4 through silencing of genes or inhibitors can downregulate GLO1 expression. Subsequent validation experiments demonstrated that GLO1 protein levels were downregulated in MEC-1 and Jurkat cell lines after palbociclib exposure, and combination treatment of palbociclib with GLO1 inhibitor BBGC effectively delayed the growth of tumor cell lines.

Rationale: Congenital factor VII deficiency is the most common among rare bleeding disorders, characterized by spontaneous or traumatic bleeding. The clinical manifestation is heterogeneous, ranging from asymptomatic phenotype to life-threatening hemorrhages. Intracranial hemorrhage is a common complication of brain tumor neurosurgery, which significantly challenges the perioperative management of patients with hemostatic defects.Patient concerns: This report presented a 55-year-old man with congenital factor VII deficiency, who had no history of hemorrhage or family history. He underwent a craniotomy for the treatment of papillary craniopharyngioma.Diagnoses: The patient was diagnosed as papillary craniopharyngioma, factor VII deficiency, and atrial fibrillation.Interventions: To prevent bleeding, a total of 8 doses of recombinant activated factor VII and 1 dose of fresh frozen plasma were administered as the perioperative replacement therapy. This scheme was guided by a pharmacodynamic evaluation, laboratory tests, and imaging examinations.Outcomes: No excessive surgical bleeding was observed during the 22-day treatment. The patient was found to have compound heterozygous mutations, Ala304Thr (c.910G > A) and IVS5-2A > G (c.572-2A > G), in the F7 gene.Lessons: This is the first reported case in which surgical hemorrhage secondary to brain tumor resection was successfully controlled in the presence of congenital factor VII deficiency. Perioperative coagulation state, hemostasis, and thrombosis events should be closely observed, and the interval and dosage of recombinant factor VIIa should be adjusted accordingly.

In area where alpha-thalassemia and beta-thalassemia are prevalent, the coinheritance of hemoglobin H disease (Hb H disease) and beta-thalassemia are not uncommon and could result in complex thalassemia intermedia syndromes. In this study, we investigate the hematological and molecular characteristics of two previously undescribed cases that co-inherited Hb H disease and rare beta-globin gene (HBB) mutations found in Chinese populations. Proband I was a boy with Hb H disease in association with IVS-II-5(G > C) (HBB:c0.315 + 5G > C) mutation. Proband II was a boy with a combination of Hb H and Hb Zengcheng [alpha 114(G16) Leu > Met; HBB:c.343C > A]. Both of them had mild hypochromic microcytic anemia, and neither had ever received a blood transfusion. In both cases, the level of Hb A(2) was within normal range, and no Hb H was detected, but a small amount of Hb Bart's was observed in proband I. Routine DNA analysis detected the deletional Hb H disease in both cases. IVS-II-5(G > C) (HBB:c0.315 + 5G > C) and Hb Zengcheng (HBB:c.343C > A) mutations were found by DNA sequencing of beta-globin gene. The co-inheritance of Hb H disease with rare beta-thalassemia may result in an atypical pattern of Hb H disease, and further investigation of rare genotypes should be conducted to avoid missed diagnosis.

We aimed to investigate the mechanism of action of Zhimu in the treatment of ovarian cancer (OC) using network pharmacology. OC targets were screened using the DisGeNET and Online Mendelian Inheritance in Man databases. Common OC and Zhimu targets were identified using the Traditional Chinese Medicine System Pharmacology, UniProt databases, and Venny 2.1.0. The protein-protein interaction (PPI) network in the Search Tool for the Retrieval of Interacting Genes/Proteins database was created using Zhimu/OC targets and a Zhimu active ingredient-target-pathway network in the Cytoscape 3.9.1 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted using the Metascape database. And overall, 15 active ingredients in addition to 93 related targets were identified. The PPI network had 52 targets that overlapped with it, with the 10 most relevant targets being the tumour protein p53, tumour necrosis factor, serine/threonine kinase 1, vascular endothelial growth factor A, caspase-3, prostaglandin G/H synthase-2, hypoxia-inducible factor-1 alpha, interleukin-1 beta, heat-shock protein 90-alpha, and progesterone receptor. According to GO and KEGG analyses, Zhimu and OC had the nuclear factor NF-kappaB signalling pathway, oxidative stress, and the advanced glycation end product (AGE)/the receptor for the advanced glycation end product (RAGE) signalling pathway as common targets. This study highlighted the active ingredients in Zhimu and identified potential molecular therapeutic mechanisms for the treatment of OC. It also provided suggestions and directions for future research into molecular mechanisms.

Background: A typical cancerous growth in the urinary tract, bladder cancer (BLCA) has a dismal survival rate and a poor chance of being cured. The cytoskeleton has been shown to be tightly related to tumor invasion and metastasis. Nevertheless, the expression of genes associated with the cytoskeleton and their prognostic significance in BLCA remain unknown. Methods: In our study, we performed differential expression analysis of cytoskeleton-related genes between BLCA versus normal bladder tissues. According to the outcomes of this analysis of differentially expressed genes, all BLCA cases doing nonnegative matrix decomposition clustering analysis be classified into different molecular subtypes and were subjected to Immune cell infiltration analysis. We then constructed a cytoskeleton-associated gene prediction model for BLCA, and performed risk score independent prognostic analysis and receiver operating characteristic curve analyses to evaluate and validate the prognostic value of the model. Furthermore, enrichment analysis, clinical correlation analysis of prognostic models, and immune cell correlation analysis were carried out. Results: We identified 546 differentially expressed genes that are linked to the cytoskeleton, including 314 up-regulated genes and 232 down-regulated genes. All BLCA cases doing nonnegative matrix decomposition clustering analysis could be classified into 2 molecular subtypes, and we observed differences (P < .05) in C1 and C2 immune scores about 9 cell types. Next, we obtained 129 significantly expressed cytoskeleton-related genes. A final optimized model was constructed consisting of 11 cytoskeleton-related genes. Survival curves and risk assessment predicted the prognostic risk in both groups of patients with BLCA. Survival curves and receiver operating characteristic curves were used to evaluate and validate the prognostic value of the model. Significant enrichment pathways for cytoskeleton-associated genes in bladder cancer samples were explored by Gene set enrichment analysis enrichment analysis. After we obtained the risk scores, a clinical correlation analysis was performed to examine which clinical traits were related to the risk scores. Finally, we demonstrated a correlation between different immune cells. Conclusion: Cytoskeleton-related genes have an important predictive value for BLCA, and the prognostic model we constructed may enable personalized treatment of BLCA.

Abstract Background Bladder carcinoma (BLCA) is a prevalent malignancy in the urinary tract and is known for its aggressive nature and high probability of recurrence. The regulation of the biological response during tumor proliferation and metastasis is inextricably linked to liquid-liquid phase separation (LLPS). To facilitate early detection and treatment, this study utilized transcriptomic data to explore the prognostic roles of LLPS-linked genes and develop a predictive model.Methods The dataset of bladder cancer patients consisted of clinical and transcriptomic data retrieved from the GEO and TCGA databases. The study utilized a clustering algorithm that employed non-negative matrix factorization (NMF) to classify the samples, which were further compared systematically for their liquid-liquid phase separation characteristics. A multivariate Cox regression model and the Least Absolute Shrinkage Selection Operator (LASSO) algorithm were utilized to construct prognostic models to establish risk formulas for nine genes. Validation of the gene signature was conducted in the entire TCGA cohort (406 cases), TCGA testing cohort (120 cases), and the external validation dataset GSE13507. The signature system was evaluated using both receiver operating characteristic (ROC) and Kaplan-Meier curves. Furthermore, decision curve analysis including the clinicopathological parameters and genetic signature was utilized to predict individual survival.Results In the study, two distinct molecular subtypes were identified, namely C1 and C2. It was revealed that individuals with the C1 subtype had a significantly more favorable prognosis as compared to those with the C2 subtype. Patients belonging to the low-risk group had remarkably better prognoses compared to those in the high-risk groups across the entire TCGA, GEO, and TCGA training cohorts. In addition, the LLPS-related gene model constructed in the study was validated as a prognostic factor independent of other clinical traits.Conclusions This study identifies gene clusters associated with LLPS and establishes a model that can predict, accurately and independently, the prognosis of BLCA. This model can be utilized in clinical practice to assess the prognosis of BLCA.

目的 探讨血清抗米勒管激素(AMH)联合黄体生成素(LH)与卵泡刺激素(FSH)比值(LH/FSH)对多囊卵巢综合征(PCOS)的诊断价值.方法 选取2020年1月至2021年5月在广西壮族自治区生殖医院确诊的112例PCOS患者作为PCOS组,并选取同期入院体检的非PCOS健康女性87例作为对照组.用罗氏Cobas e601全自动电化学发光分析仪检测两组的血清AMH、LH、FSH水平,计算LH/FSH比值,比较两组检测指标水平差异,采用受试者工作特征(ROC)曲线探究血清AMH水平联合LH/FSH比值对PCOS的诊断价值.结果 PCOS组的AMH、LH水平及LH/FSH比值高于对照组,FSH水平低于对照组,差异均有统计学意义(P<0.05).ROC曲线分析显示,血清AMH水平联合LH/FSH比值诊断PCOS的曲线下面积(AUC=0.901,95％CI:0.858～0.943)最大,敏感度和特异性分别为83.0％和81.6％.结论 PCOS患者血清AMH水平和LH/FSH比值高于非PCOS健康女性,两者联合检测对PCOS有较高的诊断价值,可作为有效的参考指标,值得临床推广应用.