High Expression Group Research Articles

Oncogene OSTM1 Promotes Gastric-Cancer Metastasis by Modulating the Metastatic Microenvironment Through Altered Tumor-Cell Autocrine Signaling

Gastric cancer remains a malignancy with high incidence, mortality rates, and poor prognosis globally. Osteoclastogenesis-associated transmembrane protein 1 (OSTM1), a transmembrane protein overexpressed in various tumors, has unclear functions in gastric-cancer progression. This study explores OSTM1’s role in gastric-cancer proliferation and metastasis. OSTM1 expression was analyzed in gastric-cancer and adjacent tissues using immunohistochemistry and RT-qPCR. OSTM1 overexpression and knockdown cell lines were established to assess its effects on cancer-cell behavior through in vitro and in vivo experiments. Western blot and RT-qPCR were used to examine OSTM1’s regulation of S100A4 expression. OSTM1 was significantly overexpressed in gastric-cancer tissues, negatively correlating with TNM staging and overall survival. OSTM1 overexpression enhanced cancer-cell proliferation, colony formation, migration, and invasion, while its knockdown showed opposite effects. In vivo studies confirmed increased lung metastatic capability in high OSTM1-expressing cells. Mechanistically, OSTM1 positively regulated S100A4 expression, with S100A4 knockdown reducing OSTM1-enhanced metastasis. Gastric-cancer lung metastases showed higher microvascular density and α-SMA-positive fibroblast infiltration in the OSTM1 high-expression group. OSTM1 promotes gastric-cancer progression by upregulating S100A4 and modifying the tumor microenvironment through enhanced angiogenesis and fibroblast activation. OSTM1 represents a potential diagnostic and prognostic biomarker, with the OSTM1–S100A4 axis offering new therapeutic possibilities for gastric-cancer treatment.

Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer.

Primary chemoresistance to platinum-based treatment is observed in approximately 33% of individuals diagnosed with ovarian cancer; however, conventional clinical markers exhibit limited predictive value for chemoresistance. This study aimed to discover new genetic markers that can predict primary resistance to platinum-based chemotherapy. Through the analysis of three GEO datasets (GSE114206, GSE51373, and GSE63885) utilizing bioinformatics methodologies, we identified two specific genes, MFAP4 and EFEMP1. The findings revealed that the areas under the receiver operating characteristic curves for MFAP4 and EFEMP1 were 0.716 and 0.657 in the training cohort, and 0.629 and 0.746 in the testing cohort, respectively. In all cases or in cases treated with platin, high expression of MFAP4 and EFEMP1 was linked to shortened overall survival and progression-free survival. MFAP4 and EFEMP1 were positively correlated with epithelial-mesenchymal transition, TGF-β signaling, KRAS signaling, and so on. The high expression groups of MFAP4 and EFEMP1 exhibited elevated stromal, immune, and ESTIMATE scores. Finally, we constructed a regulatory network involving lncRNA-miRNA-mRNA interactions. In summary, MFAP4 and EFEMP1 have the potential to serve as predictive indicators for both response to platinum-based chemotherapy and survival rates, and might be regarded as innovative biomarkers and therapeutic targets for OC patients.

Exploring potential therapeutic targets for small cell lung cancer based on transcriptomics combined with Mendelian randomization analysis

ObjectiveThe main objective of this study was to explore and identify new genetic targets in small-cell lung cancer (SCLC) through transcriptomics analysis and Mendelian randomization (MR) analysis, which will help in the subsequent development of new therapeutic interventions.MethodsIn this study, we extracted the SCLC dataset from the Gene Expression Omnibus (GEO) database, processed the data, and screened out differentially expressed genes (DEGs) using R software. Based on expression quantitative trait loci data and the genome-wide association study data of SCLC, MR analysis was used to screen the genes closely related to SCLC disease, which intersect with DEGs to obtain co-expressed genes (CEGs), and the biological functions and pathways of CEGs were further explored by enrichment analysis. In addition, the CIBERSORT algorithm was applied to assess the level of immune cell infiltration in SCLC and to analyze the correlation between CEGs and immune cells. Meanwhile, we performed a survival analysis on these five CEGs using an independent cohort of SCLC patients. Finally, the results for the target genes were validated.ResultsIn this study, 857 DEGs were identified, including 443 up-regulated and 414 down-regulated genes, and 5 CEGs (PSAT1, PSRC1, COLEC12, PLLP, HP) that were significantly associated with SCLC were identified through further intersecting. The results of enrichment analyses indicated that CEGs play important roles in several key functions and pathways. Immune-cell-related analysis revealed the unique distribution of immune cell infiltration in SCLC and the mechanism of immune cell regulation by CEGs. Survival analysis results indicated that PSRC1 was significantly correlated with the overall survival of SCLC, and the survival rate of the high-expression group was markedly lower than that of the low-expression group. Finally, the consistency of the results between the validation group analyses and MR analysis confirmed that the results of this study is reliable.ConclusionThe CEGs and their associated functions and pathways screened in this study may be potential targets of therapeutic intervention in SCLC by targeting specific molecular pathways.

ERBB3-related gene PBX1 is associated with prognosis in patients with HER2-positive breast cancer

BackgroundHER2-positive breast cancer (BC) is a subtype of breast cancer. Increased ERBB3 expression has been implicated as a potential cause of resistance to other HER-targeted therapies. Our study aimed to screen and validate prognostic markers associated with ERBB3 expression by bioinformatics and affecting the prognosis of HER2 staging.MethodsAnalyzing differences in ERBB3-related groups. ERBB3 expression-related differentially expressed genes (DEGs) were identified and intersected with survival status-related DEGs to obtain intersected genes. Three algorithms, LASSO, RandomForest and XGBoost were combined to identify the signature genes. we construct risk models and generate ROC curves for prediction. Furthermore, we delve into the immunological traits, correlations, and expression patterns of signature genes by conducting a comprehensive analysis that encompasses immune infiltration analysis, correlation analysis, and differential expression analysis.ResultsSignificant variability in ERBB3 expression and prognosis in high and low ERBB3 expression groups. Twenty-five candidate DEGs were identified by intersecting ERBB3-related DEGs with survival-related DEGs. Utilizing three distinct machine learning algorithms, we identified three signature genes-PBX1, IGHM, and CXCL13-that exhibited significant diagnostic value within the diagnostic model. In addition, the risk model had better prognostic and predictive effects, and the immune infiltration analysis showed that IGHM, CXCL13 might affect the proliferation of BC cells through immune cells. Functional studies demonstrated that interference with PBX1 inhibited the proliferation, migration, and epithelial-mesenchymal transition process of HER2-positive BC cells.ConclusionPBX1, IGHM and CXCL13 are associated with the expression level of the ERBB3 and are prognostic markers for HER2-positive in BC, which may play an important role in the development and progression of BC.

Exploring the role of ELOVLs family in lung adenocarcinoma based on bioinformatic analysis and experimental validation

BackgroundThe role of lipid metabolic reprogramming in the development of various types of cancer has already been established. However, the exact biological function and significance of the elongation of very-long-chain fatty acids (ELOVLs) gene family, which can affect fatty acid metabolism, is still not well understood in lung adenocarcinoma (LUAD). The aim of our study is to explore whether there are genes related to the pathogenesis of LUAD in the ELOVLs family, and even to guide clinical medication and potential prognostic indicators.MethodsGene expression profiling interactive analysis (GEPIA), human protein atlas (HPA), cBioPortal, Kaplan–Meier (KM) plotter, single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm and SubMap algorithms were utilized to analyze the role of ELOVLs in the LUAD. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, cell counting kit-8 (CCK8), colony formation, wound healing, transwell migration assays and fatty acid metabolism detection were employed to confirm the significant role of ELOVL6 in vitro experiment.ResultsOur results revealed that mRNA expression levels of ELOVL2, ELOVL4 and ELOVL6 and protein expression levels of ELOVL5 and ELOVL6 were elevated in LUAD tissues compared to normal subjects. The low-expressing ELOVL6 group showed superior overall survival (OS) and disease-specific survival (DSS) versus the high-expressing group. Meanwhile, patients with low-ELOVL6 expression were more sensitive to the 4 representative chemotherapeutic agents. In vitro, we revealed that interfering with ELOVL6 could influence the viability, proliferation, migration capacity and fatty acid metabolism of LUAD cells (A549 and H1299).ConclusionsOur study indicated that ELOVL6 could be used as an indicator to evaluate the prognosis and therapeutic effect, and even potential therapeutic target for patients with LUAD.

A Comprehensive Analysis of the Clinical Significance and Underlying Oncogenic Roles of Specific MMPs in Gastric Carcinoma Reveals their Potential Roles in Prognosis and Therapy.

Gastric cancer is a major global cause of cancer-related deaths, necessitating investigation into Matrix Metalloproteinases' (MMPs) diagnostic and prognostic value. Our study aimed to analyze their significance in gastric cancer. We evaluated MMP family genes' mRNA and protein expression using the University of Alabama at Birmingham (UALCAN) and Human Protein Atlas (HPA) databases. Then, we analyzed the relationship between their mRNA expression and gastric cancer staging and survival using Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan-Meier plotter. Furthermore, we assessed this family's gene mutation rates in gastric cancer patients using Search Tool for the Retrieval of Interaction Genes/Proteins (STRING) and explored potential pathways and mechanisms via Database for Annotation, Visualization, and Integrated Discovery (DAVID), cBioPortal, and R. Finally, we established a predictive model for gastric cancer based on these analyses to understand these genes' roles in cancer. Our findings revealed significantly upregulated mRNA expression of MMP1/2/3/7/9/10/11/12/13/14 in gastric cancer tissues (p<0.05). Higher levels of MMP2/7/10-encoded proteins (middle or high) were observed in tumor tissues, with MMP2/11/14 closely associated with different cancer stages (p<0.05). Additionally, MMP2/7/11/14/20 mRNA levels correlated with short-term overall survival (about 20 months), while MMP1/3/9/12/13 expression was associated with favorable overall survival (about 30 months). Gastric cancer patients exhibited a 21% mutation rate of MMP family genes, which correlated with favorable overall survival. Enrichment analysis and protein-protein interaction results underscored the close association of MMPs with gastric cancer development. The MMP2 model demonstrated a significant decline in survival rates for the high expression group, with a Hazard Ratio (HR) of 1.78 (95% CI 1.47-2.16) and a log-rank P value of 2.9e-09. Statistical significance was set at p < 0.05. Univariate Cox regression identified MMP2 as a risk factor for gastric cancer patients. Our findings highlighted MMPs' essential role in gastric cancer progression, impacting patient survival. MMP2 emerged as a promising target for gastric carcinoma detection and treatment.

Development and Validation of a Prognostic Molecular Phenotype and Clinical Characterization in Grade III Diffuse Gliomas Treatment with Radio-Chemotherapy.

The relationship between molecular phenotype and prognosis in high-grade gliomas (WHO III and IV, HGG) treated with radiotherapy and chemotherapy is not fully understood and needs further exploration. The HGG patients following surgery and treatment with radiotherapy and chemotherapy. Univariate and multivariate Cox analyses were used to assess the independent prognostic factors. The nomogram model was established, and its accuracy was determined via the calibration plots. A total of 215 and 88 patients had grade III glioma and grade IV glioma, respectively. Grade III oligodendroglioma (OG-G3) patients had the longest mPFS and mOS than other grade III pathology, while grade III astrocytoma (AA-G3) patients were close to IDH-1 wildtype glioblastoma (GBM) and had a poor prognosis. The IDH-1 mutant group had a better mPFS and mOS than the IDH-1 wildtype group in all grade III patients, OG-G3 and AA-G3 patients. Furthermore, 1p/19q co-deletion group had a longer mPFS and mOS than 1p/19q non-deletion group in all grade III patients. IDH-1 mutation and 1p/19q co-deletion patients had the best prognosis than other molecular types. Also, the MGMT methylation and IDH-1 mutation or 1p/19q co-deletion group had a longer mPFS and mOS than the MGMT unmethylation and IDH-1 wildtype or 1p/19q non-codeletion of grade III patients. In addition, the low Ki-67 expression group had a better prognosis than high Ki-67 expression group in grade III patients. Univariate and multivariate COX showed that 1p/19q co-deletion and MGMT methylation were the independent prognostic factors for mPFS and mOS. The calibration curve showed that the established nomogram could well predict the survival based on these covariates. The AA-G3 with IDH-1 wildtype, MGMT unmethylation or 1p/19q non-codeletion patients was resistant to radiotherapy and chemotherapy, has a poor prognosis and needs a more active treatment.

Prediction of Synchronous Serum CEA Expression Status Based on Baseline MRI Features of Primary Rectal Cancer Lesions Pre-treatment: A Retrospective Study

This study aimed to investigate the correlation between baseline MRI features and baseline carcinoembryonic antigen (CEA) expression status in rectal cancer patients. A training cohort of 168 rectal cancer patients from Center 1 and an external validation cohort of 75 rectal cancer patients from Center 2 were collected. A nomogram was constructed based on the training cohort and validated using the external validation cohort to predict high baseline CEA expression in rectal cancer patients. The nomogram’s discriminative ability and clinical utility were tested using the receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). The baseline CEA high-expression group had significantly higher MRI-detected metastatic lymph node (mLN), MRI-detected extramural vascular invasion (mEMVI), infiltrating tumor border configuration (iTBC), peritoneal invasion, annular infiltration, maximum extramural depth (MED), and tumor length than the normal CEA group (P < 0.05). Among them, MED [odds ratio (OR):1.19 (1.03–1.38), P = 0.016] and annular infiltration [OR:2.36 (1.06–5.25), P = 0.036] were independently predicting factors for high baseline CEA expression. The trained and validated model for predicting high baseline CEA expression in the training and external validation cohorts had the area under the curves (AUC) of 0.787 (95% CI 0.716–0.859) and 0.799 (95% CI 0.698–0.899), respectively. The calibration curves of both cohorts demonstrated good agreement between predicted and observed outcomes. Decision curve analysis indicated the clinical value of the nomogram. We developed a visual nomogram to predict high baseline CEA expression for patients with rectal cancer, enabling clinicians to conduct a personalized risk assessment and therapy.

STEAP3 is a potential preliminary prognostic biomarker of glioblastoma

Six-transmembrane epithelial antigen of prostate 3 (STEAP3), a member of the iron regulation protein family, is characterized by a high recurrence rate and a short survival time. Nevertheless, studies investigating the role of STEAP3 in glioblastoma (GB) are scarce. In this study, the prognostic value of STEAP3 was evaluated utilizing mRNA expression profiles from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases as the validation and training cohorts, respectively. Moreover, differentially expressed genes were subjected to a functional enrichment analysis. The relationship between STEAP3 and the tumor microenvironment (TME) was examined. The immunophenoscore (IPS) and tumor immune dysfunction and exclusion (TIDE) score were used to investigate response to immunotherapy. In all cohorts, GB patients with higher STEAP3 expression levels exhibited shorter overall survival (OS). Additionally, STEAP3-associated genes were primarily implicated in leukocyte migration, the JAK-STAT signaling pathway, and the cytokine-mediated signaling pathway. In the STEAP3 high-expression group, the ESTIMATEScore, ImmuneScore, StromalScore, and IPS were significantly higher. Overall, our results highlighted that STEAP3 might serve as a candidate prognostic biomarker for GB. Additionally, it might regulate the TME and influence GB metastasis.

Crosstalk between CD180-overexpression macrophages and glioma cells worsens patient survival through malignant phenotype promotion and immunosuppressive regulation

BackgroundUnderstanding the molecular mechanisms in immunosuppressive regulation is crucial for improving immunotherapeutic strategies. Macrophages, the major immune cells in tumor microenvironment (TME), play a dual role in tumor progression. CD180, primarily expressed in macrophages, remains unclear and requires further investigation.MethodsRNA-seq data were obtained to analyze CD180 expression in gliomas and assess its prognostic value. The comprehensive immune infiltration analysis was performed. Single-cell RNA-seq (scRNA-seq) data were used to examine CD180 expression distribution at the cellular level. CD180-overexpression macrophages were co-cultured with three glioma cell lines. The effects on glioma cell behavior were evaluated through qRT-PCR, Western blot, CCK-8 assay, EdU assay, Transwell assay, TUNEL assay, and flow cytometry. Differentially expressed genes (DEGs) and their potential biological functions were analyzed between different CD180 expression groups. Consensus clustering was used to identify CD180-related glioma subtypes.ResultsCD180 was significantly upregulated in glioma samples and associated with poor prognosis. High CD180 expression was correlated with increased immune cell infiltration, particularly macrophages, and elevated levels of immune checkpoints. Analysis of scRNA-seq data revealed the predominant expression of CD180 in macrophages within the glioma TME. In vitro experiments demonstrated that CD180-overexpression macrophages promoted glioma cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while decreasing apoptosis. Mutations in TP53 and PTEN were significantly more prevalent in the high CD180 expression group. We identified nine chemotherapeutic agents that were more effective in glioma patients with high CD180 expression. Additionally, two CD180-related glioma subtypes with distinct prognosis were identified.ConclusionsThis study confirmed the prognostic role of CD180 in glioma and its involvement in immunosuppressive regulation and malignant phenotype promotion. Therefore, CD180 was considered as a promising target for immunotherapeutic strategies in glioma treatment.

The expression and clinical significance of serum exosomal-long non-coding RNA DLEU1 in patients with cervical cancer

Background Accumulating evidence has demonstrated that the long non-coding RNA (lncRNA) lymphocytic leukaemia deletion gene 1 (DLEU1) is abnormally overexpressed in many cancer types, including cervical cancer (CC). However, the potential clinical significance of DLEU1 in serum exosomes of patients with CC remains unclear. Methods The expression of serum exosomal DLEU1 was detected by quantitative real-time polymerase chain reaction (qRT-PCR). A receiver operating characteristic (ROC) curve was plotted to evaluate the clinical diagnostic efficacy of DLEU1. The Kaplan–Meier survival curve and Cox proportional hazards model were used to assess the effect of DLEU1 on postoperative recurrence, metastasis and prognosis among patients with CC. Results Our research showed that DLEU1 expression in the serum exosomes of patients with CC was significantly upregulated compared to that in patients with cervical intraepithelial neoplasia (CIN) and healthy controls (HCs) (both p < .001). DLEU1 relative expression was significantly correlated with tumour size, cervical invasion depth, pathological grade, International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis among patients with CC (p < .01 all). The combined detection of DLEU1, carbohydrate antigen 125 (CA-125) and squamous cell carcinoma (SCC) exhibited significantly higher diagnostic efficiency (p < .01). Furthermore, the overall survival (OS) and disease-free survival (DFS) of CC patients in the high DLEU1 expression group were markedly lower than those in the low DLEU1 expression group (both p < .01). Cox univariate and multivariate regression analyses indicated that DLEU1 was an independent risk factor for postoperative recurrence and metastasis in CC patients. Conclusions Our findings suggest that serum exosome DLEU1 has certain clinical value for diagnosing, monitoring recurrence and metastasis, and evaluating CC prognosis.

Clinical value of serum miRNA-206 in pulmonary tuberculosis.

This study sought to investigate the diagnostic value and the effect of microRNA (miR)-206 on drug resistance in pulmonary tuberculosis (TB) patients. This study included 88 TB patients (TB group) as study subjects, 80 healthy subjects as control 1 (Control group), and 85 latent TB infection (LTBI) patients as control 2 (LTBI group). The drug resistance of TB patients after standard anti-TB treatment was recorded. TB patients were assigned into the pan-sensitive and drug-resistance groups, with miR-206 level in drug-resistant TB patients analyzed. The correlation coefficients between inflammatory indicators (TNF-α, IgG, IL-4, IFN-γ, IP-10) and drug resistance in TB patients were analyzed, and the independent correlation between miR-206 levels and drug resistance was analyzed. Compared to the Control and LTBI groups, serum miR-206 and IP-10 were highly-expressed in TB group. The miR-206 levels positively correlated with IP-10 levels. miR-206 had potential diagnostic value for TB. Levels of TNF-α, IgG, IFN-γ, and IL-4 were elevated in TB group and positively-correlated with miR-206 levels. Moreover, miR-206 levels were higher in the Drug-resistance group than the pan-sensitive group. The low-expression group had a lower incidence of drug resistance than the high-expression group (χ2 = 16.84, P < 0.0001). miR-206 was the most significant indicator affecting drug resistance in TB patients (β = 0.516, P = 0.013). miR-206 was an independent risk factor for drug resistance. High miR-206 expression helps TB diagnosis and may predict drug-resistance incidence. miR-206 may be an independent risk factor for drug resistance in TB patients.

Study on the mechanism of liver cancer immune escape mediated by MINDY1 through regulation of PD-L1 ubiquitination level.

The novel deubiquitinase enzyme, motif interacting with ubiquitin-containing novel DUB family-1 (MINDY1), is highly expressed in liver cancer tissues and plays a crucial role in maintaining the stemness of liver cancer cells. Programmed death ligand-1 (PD-L1) is an immunosuppressive molecule overexpressed by tumour cells. The potential role of MINDY1 in inhibiting the stemness of liver cancer cells by deubiquitinating PD-L1 has not yet been reported. To investigate the mechanism by which MINDY1 mediates immune escape in liver cancer through the regulation of PD-L1 ubiquitination, we examined the expression levels of MINDY1 and PD-L1 in liver cancer and adjacent tissues from 50 hepatocellular carcinoma (HCC) patients using protein imprinting and immunohistochemistry. We analyzed the relationship between the expression levels of MINDY1 and PD-L1 in liver cancer tissues and their correlation with the 5-year tumor-free survival rates of patients. Subsequently, MINDY1 expression was knocked down in Huh7 cells using small interfering RNA (siRNA) interference or upregulated through transfection with a MINDY1 overexpression plasmid. The effects of MINDY1 knockdown or overexpression on the proliferation, apoptosis, migration, and invasion of HCC cells, as well as the regulation of PD-L1 binding and ubiquitination, were assessed. The 5-year tumor-free survival rates were significantly lower in both the high MINDY1 expression group and the high PD-L1 expression group (χ2 = 4.919 and 13.158, respectively).A significant difference in survival was observed between the high and low MINDY1 expression groups (χ2= 27.415). MINDY1 was found to directly interact with PD-L1, with MINDY1 gene knockdown promoting PD-L1 ubiquitination and MINDY1 overexpression inhibiting PD-L1 ubiquitination. All comparisons yielded statistically significant results (P < 0.05). In conclusion, MINDY1 inhibits the malignant progression of liver cancer by inhibiting PD-L1 ubiquitination and mediating immune escape.

Elevated IL-6 Expression in Autologous Adipose-Derived Stem Cells Regulates RANKL Mediated Inflammation in Osteoarthritis.

Interleukin-6 (IL-6) expression in mesenchymal stem cells (MSCs) has been shown to play a pivotal role in modulating cartilage regeneration and immune responses, particularly in the context of diseases that involve both degenerative processes and inflammation, such as osteoarthritis (OA). However, the precise mechanism through which IL-6 and other immune-regulatory factors influence the therapeutic efficacy of autologous adipose-derived stem cells (ASCs) transplantation in OA treatment remains to be fully elucidated. This study aims to investigate the relationship between IL-6 expression in autologous ASCs isolated from OA patients and their impact on immune modulation, particularly focusing on the regulation of Receptor Activator of Nuclear factor Kappa-Β Ligand (RANKL), a key mediator of immune-driven cartilage degradation in OA. Autologous ASCs were isolated from the stromal vascular fraction (SVF) of adipose tissue obtained from 22 OA patients. The isolated ASCs were cultured and characterized using reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and flow cytometry to the phenotype and immune regulatory factors of MSCs. Based on IL-6 expression levels, ASCs were divided into high and low IL-6 expression groups. These groups were then co-cultured with activated peripheral blood mononuclear cells (PBMCs) to evaluate their immune-modulatory capacity, including the induction of regulatory T cells, inhibition of immune cell proliferation, and regulation of key cytokines, such as interferon-gamma (IFN-γ). Additionally, RANKL expression, a critical factor in osteoclastogenesis and cartilage degradation, was assessed in both ASC groups. High IL-6-expressing ASCs demonstrated a significantly greater capacity to inhibit immune cell proliferation and IFN-γ production compared to their low IL-6-expressing counterparts under co-culture conditions. Moreover, the group of ASCs with high IL-6 expression showed a marked reduction in RANKL expression, suggesting enhanced potential to control osteoclast activity and subsequent cartilage defect in OA. Conclusion: Autologous ASCs with elevated IL-6 expression exhibit enhanced immunomodulatory properties, particularly in regulating over-activated immune response and reducing osteoclastogenesis through RANKL suppression. These findings indicate that selecting ASCs based on IL-6 expression could enhance the therapeutic efficacy of ASC-based treatments for OA by mitigating immune-driven joint inflammation and cartilage degradation, potentially slowing disease progression.

Prediction of HIF-1α expression in endometrial carcinoma by enhanced T2 ∗ weighted angiography and dynamic contrast-enhanced magnetic resonance imaging.

To explore the value of quantitative imaging parameters by enhanced T2 * weighted angiography (ESWAN) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for evaluating the expression of Hypoxia-inducible factor-1α (HIF-1α) in endometrial carcinoma (EC). Data from 122 patients with EC confirmed by clinical pathology were retrospectively analyzed. According to the number of positive cells stained with HIF-1α by immunohistochemistry, patients were divided into two groups: 65 cases with high expression of HIF-1α and 57 cases with low expression of HIF-1α. Clinical data included age, FIGO stage, menopausal status, abnormal uterine bleeding, and pathological type. All patients underwent preoperative 1.5T MRI scans, including ESWAN and DCE-MRI. The amplitude, phase, and R2 * values derived from ESWAN and the volume transfer constant (Ktrans), rate constant (Kep), and extravascular volume fraction (Ve) values derived from DCE-MRI were measured by two observers, respectively. The intra-class correlation coefficient (ICC) was used to assess the measurement of reproducibility across observers, and the differences in imaging parameters between the two groups were compared using the independent sample t-test or Mann-Whitney U-test. Binary logistic regression analysis was used to find independent risk factors for HIF-1α expression. The efficacy of selected imaging parameters for predicting HIF-1α expression was assessed using receiver operating characteristic (ROC) curves, and the Delong test was used to compare the area under ROC curves (AUC). The consistency between the two observers was good (ICC>0.75). The R2 *, Ktrans, and Kep values of the HIF-1α high expression group were higher than those of the HIF-1α low expression group (14.59 ± 4.06 vs. 11.99 ± 2.84 Hz, 0.45 ± 0.18 vs. 0.36 ± 0.14/min, and 2.17 ± 1.10 vs. 1.54 ± 0.80/min) (P< 0.001, P = 0.011, and P =0.001). Binary logistic regression analysis revealed that R2 * and Kep values were independent risk factors for HIF-1α expression. The AUC values of R2 *, Kep, and their combination for prediction of HIF-1α expression were 0.697, 0.677, and 0.781, respectively. The diagnostic efficacy was significantly improved with combination of R2 * and Kep. Quantitative parameters by ESWAN and DCE-MRI showed significant differences between EC patients with low and high expression of HIF-1α, and the combination of ESWAN and DCE-MRI improves the efficacy in prediction of HIF-1α expression in EC, which has an excellent clinical application prospect.

Clinicopathological significance of sulfite oxidase expression in surgically resected lung adenocarcinoma.

The coenzyme sulfite oxidase (SUOX), located in mitochondria, plays a role in redox and metabolism. Its expression has been associated with cancer progression and prognosis. Lung cancer has a high incidence rate and poor prognosis. We aim to clarify its expression in lung adenocarcinomas and investigated the utility of SUOX expression as a recurrence factor in operable lung adenocarcinoma. We used 60 formalin-fixed paraffin-embedded samples of operable primary lung adenocarcinoma between 2017 and 2018 to immunohistochemically assess SUOX expression levels. Patients were classified into a high or low SUOX expression group, and the associations of SUOX expression with clinicopathological findings and recurrence were analyzed. We revealed that high SUOX expression was significantly (p < 0.05) associated with sex, low Brinkman index, histological type, histological grade and positive for epidermal growth factor receptor (EGFR) mutation. High SUOX expression (HR = 10.218, 95% CI 1.758‒59.376, p = 0.0096) and pathological Stage (HR = 7.538, 95% CI 1.95‒29.14, p = 0.0034) were independently associated with relapse free survival. High SUOX expression may be a new indicator of recurrence risk in surgically resected lung adenocarcinomas.

BUD23 promote the cell proliferation ability by affecting the PPAR signaling pathways: evidence from the online dataset and cell experiment

IntroductionProstate cancer is a major public health challenge for men worldwide, being the second most common cancer diagnosis and the fifth leading cause of cancer-related deaths among men. The etiology of prostate cancer is multifactorial, with age, genetic predispositions, and lifestyle factors playing critical roles. The role of the peroxisome proliferator-activated receptors (PPARs) in prostate cancer remains complex and not fully elucidated.MethodsTranscriptomic data from The Cancer Genome Atlas (TCGA) were utilized for this study. The data were analyzed using single-sample Gene Set Enrichment Analysis (ssGSEA), Gene Ontology (GO) enrichment analysis, KEGG pathway analysis, and Gene Set Enrichment Analysis (GSEA). A prognosis-prediction model was constructed using Cox regression and LASSO analysis. Functional experiments, including Western blotting, quantitative PCR (qPCR), Cell Counting Kit-8 (CCK-8) assays, and EdU incorporation assays, were performed to validate the role of BUD23 in prostate cancer.ResultsSignificant differences were observed in the immune microenvironment and HLA gene expression profiles between high and low PPAR expression groups in prostate cancer. The high PPAR group exhibited a less active immune microenvironment with higher fractions of immunosuppressive T regulatory cells (Tregs). A robust prognostic model identified key genes, including BUD23, associated with patient survival. Elevated BUD23 expression was correlated with more aggressive clinical features such as advanced pathological stages, nodal metastasis, and higher Gleason scores. Knockdown of BUD23 in PC-3 and LNCaP prostate cancer cell lines significantly inhibited cell proliferation. Western blotting and qPCR confirmed effective BUD23 knockdown, and CCK-8 and EdU assays demonstrated reduced cell proliferation. BUD23 knockdown resulted in significant reductions in PPAR-α, PPAR-β, and PPAR-γ protein levels, suggesting a regulatory axis between BUD23 and PPARs in prostate cancer.ConclusionThe study highlights the distinct roles of PPARα, PPARβ/δ, and PPARγ in prostate cancer progression and their potential as therapeutic targets. Elevated BUD23 expression is associated with aggressive prostate cancer features and patient survival, making it a potential prognostic biomarker. The knockdown of BUD23 not only inhibited cell proliferation but also reduced the expression of PPAR-related proteins, indicating a potential regulatory axis between BUD23 and PPARs. These findings suggest that targeting BUD23 could modulate PPAR signaling and inhibit tumor growth in prostate cancer.

PLEK2: a potential biomarker for metastasis and prognostic evaluation in uveal melanoma.

Uveal melanoma (UVM) is an aggressive tumor known for its high metastatic rate, making it necessary to delineate potential molecules that may promote the development of UVM. PLEK2 has been found to promote the progression and metastasis of some tumors, but its role in UVM has not yet been reported. Through this study, we hope to explore the effect of PLEK2 on the prognosis of UVM patients and to discover the potential functional role and intrinsic mechanism of PLEK2. The GEO datasets GSE211763 and GSE149920 were analyzed using GEO2R to identify differentially expressed genes that may be associated with UVM progression and metastasis. A Protein-Protein Interaction Network (PPI) was constructed to identify key molecules. The correlation between PLEK2 expression and overall survival was evaluated via GEPIA2, and clinical characteristics of UVM patients were compared based on PLEK2 levels. PLEK2 expression in UVM cell lines was assessed using the CCLE database and confirmed by qPCR and western blot. A weighted correlation network analysis (WGCNA) was performed, followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, a search for miRNAs potentially regulating PLEK2 expression was performed using TargetScan, miRWalk, and TarBase databases. Comparative analysis of the GEO datasets unveiled 79 commonly up-regulated genes and 238 commonly down-regulated genes. The PPI network identified 9 hub genes, with PLEK2 significantly linked to reduced overall survival. Clinical comparisons indicated significant differences in cancer status (p = 0.013) and tumor diameter (p = 0.039) between high and low PLEK2 expression groups. Elevated PLEK2 mRNA levels were confirmed in UVM cell lines compared to retinal pigment epithelial cells. PLEK2 was enriched in the calcium signaling pathway and associated with the Wnt/Ca2+ signaling pathway. A total of 21 miRNAs potentially regulating PLEK2 were predicted. PLEK2 is upregulated in UVM and correlates with poor patient prognosis, likely influencing the calcium signaling pathway. PLEK2 represents a promising prognostic biomarker and therapeutic target for UVM.

Fibroblast Activation Protein-α Expression in Cancer-Associated Fibroblasts Shows the Poor Survival of Colorectal Cancer via Immune-Mediated Pathways : Implications of FAP in Cancer-Associated Fibroblasts Link Immune Dysregulation to Adverse Survival in Colorectal Cancer.

Cancer-associated fibroblasts (CAFs) and immune cells, the key components of the tumor microenvironment (TME), play critical roles in oncogenesis. Despite the recognized function of fibroblast activation protein-α (FAP), a specific biomarker of CAFs in cancer progression, its role in the survival of patients with colorectal cancer (CRC) and tumor immune microenvironment (TIME) remains unclear. We investigated 180 pathological sections obtained from 178 consecutive patients with CRC who underwent surgical resection at Shiga University of Medical Science Hospital between January 2013 and December 2015. FAP expression levels and CD3 and CD8 densities at the invasive margin and center of tumor were assessed using immunohistochemical (IHC) staining. Furthermore, we used single-cell RNA sequencing (scRNA-seq) of CAFs in a separate cohort of 10 untreated patients with CRC derived from the Gene Expression Omnibus database. According to IHC evaluation, high FAP expression in patients with CRC showed a correlation with reduced tumor-infiltrating lymphocyte (TIL) distribution and poor survival. Based on the FAP transcription levels obtained through scRNA-seq analysis, CAFs were grouped into high and low FAP expression groups. Elevated FAP expression was correlated with decreased expression of T- and B-cell biomarkers, suggesting an association with an immunosuppressive TME promotion. Several genes associated with cancer-related immune-mediated pathways (CXCL12, COL11A1, CCL11, and COL10A1) were significantly upregulated in FAP-positive CAFs. This study highlights the effects of FAP expression on survival of patients with CRC, its interaction with TILs, and relevant signaling pathways, and underscores potential immunotherapeutic targets for future investigation.

Preoperative prediction of Ki-67 expression in hepatocellular carcinoma by spectral imaging on dual-energy computed tomography (DECT).

The Ki-67 expression level, which represents the proliferation status of cells, serves as a prognostic marker for hepatocellular carcinoma (HCC); however, the immunochemistry method currently used to evaluate Ki-67 is invasive and is not suitable for patients who have lost the chance for surgery, such as those with advanced tumors or those with other serious organic diseases. This study aimed to investigate the value of quantitative dual-energy computed tomography (DECT) parameters in predicting the expression level of Ki-67 in HCC. This study analyzed the data of 123 consecutive patients with HCC who underwent both Ki-67 immunohistochemistry analysis and two-phase contrast-enhanced DECT imaging. The patients were divided into the following two groups based on the positive rate of Ki-67 (Ki-67%): the high-expression group (Ki-67% >20%, n=74); and the low-expression group (Ki-67% ≤20%, n=49). The computed tomography (CT) values in the 130 and 140 keV monochromatic energy images (HU130-140keV), normalized effective atomic number (NeffZ), fat density (Dfat), and water density (Dwater) were measured and calculated at the arterial phase (AP) and portal venous phase (PVP). A Spearman correlation coefficient analysis, a comparison of parameters between groups, a receiver operating characteristic (ROC) curve analysis for evaluating predictive efficacy, and a multivariable logistic regression analysis were conducted. The NeffZ-AP, HU130 keV-PVP, HU140 keV-PVP, Dfat-PVP, and Dwater-PVP were positively correlated with the Ki-67% (all P<0.05), and the DECT parameter values in the high-expression group were significantly higher than those in the low-expression group (all P<0.05). The Dwater-PVP [odds ratio (OR) =1.353, 95% confidence interval (CI): 1.204-1.521, P<0.001] and tumor diameter (OR =1.258, 95% CI: 1.08-1.465, P=0.003) were independent predictive factors for high Ki-67 expression. Dwater-PVP had the highest predictive efficacy with an area under the curve (AUC) of 0.810. The multivariable analysis combining the DECT parameters and morphological characteristics improved the predictive efficacy of the model in predicting high Ki-67 expression (AUC =0.857). DECT provides a non-invasive method to evaluate the proliferation status of HCC cells, and the predictive efficacy of high Ki-67 expression could be improved by combining DECT parameters and morphologic features.