Discover. Oncology最新文献

{"title":"ERCC3 serves as a prognostic biomarker for hepatocellular carcinoma and positively regulates cell proliferation and migration.","authors":"Chen Yang, Jiahui Du, Xiuqin Qiu, Changhong Jia, Cunbao Ding, Yijie Wu, Chaoxu Gao, Weijie Wang, Xiaojun Wang, Song-Bai Liu","doi":"10.1007/s12672-025-02194-y","DOIUrl":"https://doi.org/10.1007/s12672-025-02194-y","url":null,"abstract":"<p><strong>Background: </strong>ERCC3, a crucial component of the nucleotide excision repair pathway, is implicated in the development and progression of various cancers and is a potential indicator of poor prognosis. However, the expression and function of ERCC3 in hepatocellular carcinoma (HCC) remain unclear. This study aimed to investigate the expression of ERCC3 in HCC tissues and its clinical significance, focusing on elucidating its potential mechanisms and therapeutic value in immunotherapy.</p><p><strong>Methods: </strong>The differential expression and genetic variation characteristics of ERCC3 across various cancers were evaluated using the TCGA database. The expression and prognostic value of ERCC3 in HCC were analyzed by integrating TCGA, GEO, and ICGC datasets. Independent prognostic value of ERCC3 expression levels in HCC was assessed using Cox regression analysis, Kaplan-Meier survival analysis, receiver operating characteristic curves, and nomograms. Pathway association scores were determined using ssGSEA to reveal the biological functions of ERCC3 in HCC and its potential clinical efficacy in immunotherapy. Stable transient cell lines were established by infecting HepG2 cells with lentivirus overexpressing ERCC3. The effects of ERCC3 on HCC cell biological phenotypes were evaluated using RTCA, wound healing, and Transwell assays. Cell cycle distribution and apoptosis were detected by flow cytometry. Transcriptome sequencing was performed to explore the impact of ERCC3 overexpression on the expression of signaling pathway-related genes in HCC.</p><p><strong>Results: </strong>The study revealed that ERCC3 is aberrantly expressed in various tumors, with significantly higher mRNA and protein levels in HCC tissues compared to normal tissues. High ERCC3 expression was significantly correlated with poor survival outcomes in HCC patients. Multivariate Cox regression analysis revealed that ERCC3 expression level is an independent prognostic factor for overall survival (P = 0.014). Gene sets associated with the high ERCC3 group were significantly involved in multiple immune pathways and tumor progression-related pathways, and ERCC3 expression was significantly correlated with immune checkpoints in HCC. Overexpression of ERCC3 promoted the proliferation and migration of HCC cells and influenced cell cycle progression. Transcriptome sequencing analysis indicated that ERCC3 overexpression regulated the proliferation of HCC cells, participated in multiple pro-inflammatory pathways, induced the formation of an inflammatory tumor microenvironment, and promoted HCC progression.</p><p><strong>Conclusion: </strong>This study is the first to reveal the association between high ERCC3 expression and poor prognosis in HCC and to elucidate its immunomodulatory role in HCC. Unlike previous studies, we found that ERCC3 promotes HCC progression by regulating the inflammatory microenvironment and immune checkpoints. These findings establish a novel theoret","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"419"},"PeriodicalIF":2.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NEK2 promotes cancer cell progression and 5-fluorouracil resistance via the Wnt/β-catenin signaling pathway in colorectal cancer.","authors":"Facai Cui, Yu Chen, Xiaoyu Wu, Weifeng Zhao","doi":"10.1007/s12672-025-02154-6","DOIUrl":"10.1007/s12672-025-02154-6","url":null,"abstract":"<p><strong>Background: </strong>Never-in-mitosis gene A-related-kinase-2 (NEK2) plays a pivotal role in malignant progression and chemotherapy sensitivity. This study aimed to elucidate the role of NEK2 in colorectal cancer (CRC) and its potential contribution to 5-fluorouracil (5‑FU) resistance mechanisms.</p><p><strong>Methods: </strong>Quantitative real-time PCR (qRT‑PCR), western blotting, and immunohistochemical (IHC) staining were used to assess the expression of NEK2 in CRC tissues and cells. The effects of NEK2 and 5‑FU on the proliferation, apoptosis, migration, and invasion of cancer cells were investigated via Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, wound healing, and transwell assays, respectively. Methyl 3-(4-methylphenylsulfonamido) benzoate (MSAB) was used as a Wnt/beta (β)-catenin pathway inhibitor in this study.</p><p><strong>Results: </strong>NEK2 expression was significantly upregulated in CRC tissues and cells compared to normal controls. High NEK2 expression in CRC tissues was correlated with advanced tumor-node-metastasis (TNM) stage, lymph node metastasis, distant metastasis, and a poor tumor prognosis. NEK2 overexpression promoted the proliferation, migration, and invasion of CRC cells. NEK2 overexpression inhibited the cytotoxic effect of 5-FU on CRC cells. NEK2 overexpression promoted the nuclear accumulation of β-catenin and activated the Wnt/β-catenin signaling pathway. MSAB reversed the stimulatory effect of NEK2 upregulation on proliferation and resistance to 5-FU in CRC cells.</p><p><strong>Conclusions: </strong>In summary, NEK2 promotes cell survival and decreases sensitivity to 5-FU in CRC by activating the Wnt/β-catenin signaling pathway. Consequently, NEK2 holds promise as a potential therapeutic target for CRC management.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"417"},"PeriodicalIF":2.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The hidden pathway: biological aging as a mediator between diabetes and breast cancer risk: a Mendelian randomized study.","authors":"Yipang Zhao, Jingzhi Zhang, Dong Chen, Sixuan Xing, Shuhan Zhang, Qing Zhang","doi":"10.1007/s12672-025-02204-z","DOIUrl":"10.1007/s12672-025-02204-z","url":null,"abstract":"<p><strong>Objective: </strong>To explore the relationship between type 2 diabetes mellitus and the risk of developing breast cancer and its subtypes, and the mediating role of biological aging in it.</p><p><strong>Methods: </strong>A two-sample Mendelian randomized analyses were performed to assess the effect of type 2 diabetes mellitus on breast cancer and its subtypes, and the mediating effect of biological aging between type 2 diabetes mellitus with breast cancer and its subtypes was explored by mediation analysis. All the data were based on genome-wide association studies. The data of type 2 diabetes mellitus were obtained from meta-analyses with the UK Biobank and FinnGen. The data of biological aging and breast cancer were obtained from UK Biobank, Breast Cancer Association Consortium, respectively.</p><p><strong>Results: </strong>The results of univariate Mendelian randomized showed that type 2 diabetes mellitus was positively causally associated with the risk of triple-negative breast cancer (OR = 1.076, 95%CI 1.022 ~ 1.132, P = 0.005), and positively associated with the biological aging phenotype PhenoAgeAccel (OR = 1.311, 95%CI 1.221 ~ 1.407, P < 0.001) and BioAgeAccel (OR = 1.083, 95%CI 1.054 ~ 1.113, P < 0.001) were both positively causal. The results of mediation analysis showed that BioAgeAccel played a fully mediating role in the causal effect of type 2 diabetes mellitus and triple-negative breast cancer, with a mediating effect of -0.010 (95%CI -0.020 ~ -0.001).</p><p><strong>Conclusion: </strong>Through Mendelian randomized analyses, this study explores the potential causal link between type 2 diabetes mellitus and the risk of triple-negative breast cancer, as well as the possible mediating role of biological ageing. The findings indicate a potential association between type 2 diabetes mellitus and an increased risk of triple-negative breast cancer, with BioAgeAccel possibly acting as a mediator. However, given the limitations of the study and the current evidence, it is premature to definitively establish a causal relationship and the precise mediating effect. Further research is necessary to substantiate these findings.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"416"},"PeriodicalIF":2.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The development and validation of a column chart for predicting the regression risk of CIN2.","authors":"Jingjing Ren, Hui Wang, Xiu Zhang, Min Hao","doi":"10.1007/s12672-025-02160-8","DOIUrl":"10.1007/s12672-025-02160-8","url":null,"abstract":"<p><strong>Background: </strong>A predictive nomogram model was established for the prognosis of cervical intraepithelial neoplasia 2 (CIN2).</p><p><strong>Methods: </strong>This study was based on the research data of CIN2 obtained from the Shanxi CIN cohort study from 2019 to 2022. We conducted a cross-sectional analysis of 512 female patients with CIN2. Subsequently, the least absolute shrinkage and selection operator (LASSO) regression, along with univariate and multivariate regression analyses, were conducted to identify five risk factors associated with CIN2 prognosis. These factors include age at first sexual activity, ThinPrep cytologic test (TCT) results, Human papillomavirus (HPV) infection type, lesion area detected by colposcopy, and acetowhitening thickness. A predictive model was constructed employing R software. Receiver operating characteristic (ROC) curve and resampling methods were employed to evaluate the predictive model in terms of accuracy and calibration. Decision curve analysis (DCA) was performed to assess its clinical application value.</p><p><strong>Results: </strong>Women with CIN2 (n = 512) aged 19-65 were included in the study; after 6 months of follow-up, 185 showed lesion regression, and 336 showed lesion persistence or progression. The factors for the predictive model included age of sexual activity (P = 0.005), multiple sexual partners (P = 0.076), TCT results (P < 0.0001), HPV infection (P = 0.0025), lesion area (P < 0.0001), and the thickness of acetic acid stain (P < 0.0001). Subsequent ROC curve analysis showed the respective sensitivity and specificity of the predictive model to be 0.827 and 0.708. Finally, DCA, used to assess the predictive value of the 5-factor CIN2 regression predictive model, was higher than the combined predictive model of HPV and TCT.</p><p><strong>Conclusion: </strong>The study could successfully establish a model for predicting the pathological regression status of CIN2 patients.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"412"},"PeriodicalIF":2.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive identification of a migrasomes-associated long non-coding RNA signature to predict the prognosis and treatment options in colon adenocarcinoma.","authors":"Zhen Zheng, Hui Liu, Quan Xu, Wei Cui, Kaitai Liu","doi":"10.1007/s12672-025-02197-9","DOIUrl":"10.1007/s12672-025-02197-9","url":null,"abstract":"<p><strong>Background: </strong>Migrasomes, recently discovered cellular substructures, may play a crucial role in cancer progression, treatment response, and prognosis. However, the prognostic value of migrasome-associated long non-coding RNAs (lncRNAs) in colon adenocarcinoma (COAD) remains unexplored.</p><p><strong>Methods: </strong>RNA-seq data from 459 COAD patients, including clinical characteristics and outcome information, were obtained from The Cancer Genome Atlas. A risk model was constructed through co-expression analysis of migrasome genes and lncRNAs, followed by Cox regression and least absolute shrinkage and selection operator analysis to identify prognostic lncRNAs. Functional enrichment analyses were performed to elucidate underlying biological mechanisms. Immune landscape characterization utilized ESTIMATE, CIBERSORT, Tumor Immune Estimation Resource (TIME), and single-sample Gene Set Enrichment Analysis (ssGSEA). Drug sensitivity analysis was conducted for select therapeutic agents.</p><p><strong>Results: </strong>Nine prognostic lncRNAs (AC010463.3, AL590483.4, AP005264.1, ZEB1-AS1, AC104088.1, PRKAR1B-AS2, AC009315.1, SUCLG2-AS1, and AC006111.2) were identified and incorporated into a risk model. Low-risk patients demonstrated significantly improved survival outcomes. The model exhibited independent prognostic capability, with AUCs of 0.783, 0.749, and 0.713 for one-, three-, and five-year survival, respectively, in the training cohort. High-risk patients displayed reduced overall survival and elevated tumor mutation burden. Additionally, these patients showed decreased sensitivity to therapeutic agents, including Oxaliplatin, Irinotecan, and 5-Fluorouracil.</p><p><strong>Conclusion: </strong>Our novel migrasome-associated lncRNA signature demonstrates robust predictive capacity for both prognosis and chemotherapeutic sensitivity in COAD, potentially facilitating personalized treatment strategies and improved patient management.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"409"},"PeriodicalIF":2.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating ΔMTV%, ΔD_max%, and %ΔSUV_max of ¹⁸F-FDG PET/CT for mid-treatment efficacy and prognosis in diffuse large B-cell lymphoma.","authors":"Yali Cui, Yao Li, Wenhao Hu, Zhifang Wu, Sijin Li, Hongliang Wang","doi":"10.1007/s12672-025-02126-w","DOIUrl":"10.1007/s12672-025-02126-w","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the value of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging in interim therapeutic and prognostic evaluation of patients with diffuse large B-cell lymphoma (DLBCL).</p><p><strong>Materials and methods: </strong>Data of 86 patients with pathologically confirmed DLBCL who underwent ¹⁸F-FDG PET/CT imaging before chemotherapy, radiotherapy, and after interim chemotherapy, were retrospectively analyzed. Receive operating characteristic (ROC) curve analysis was performed to assess the predictive capacity of changes and change rates in PET/CT imaging parameters [maximum standardized uptake value (SUV_max), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum tumor dissemination (D_max)] for progression-free survival (PFS) and to identify optimal cutoff values. Kaplan-Meier survival curves were constructed, and the log-rank test was used to assess intergroup differences. Cox regression analysis was used to explore potential factors influencing PFS.</p><p><strong>Results: </strong>Among 86 patients [(45 men, 41 women, age: 57.8 ± 12.2 years)], the median PFS was 22.5 (14.5, 46) months. Until the last follow-up date, progression or recurrence occurred in 14 patients, while 9 patients died. The ROC curves indicated that the optimal cutoff values for predicting PFS were 99.10%, 99.72%, and 96.47% for ΔMTV%, ΔTLG%, and ΔD_max%, respectively (area under the curve = 0.786-0.849, all P < 0.05). Cox univariate analysis demonstrated that the alteration rates in metabolic and diffusion parameters before and after treatment, including SUV_max%, MTV%, TLG%, and D_max%, were predictive of PFS (hazard ratio [HR] = 6.213-13.430, all P < 0.05). The Cox multivariate analysis demonstrated that ΔMTV% and ΔD_max% independently predicted PFS, with HRs of 10.727 (95% confidence interval [CI] = 1.928-56.672, P = 0.007) and 7.178 (95%CI = 1.514-34.041, P = 0.013), respectively. We established a new prediction model by combining the ΔMTV% and ΔD_max% parameters, and the results of the model showed statistically significant differences in PFS between the high, intermediate, and low-risk groups. The model predicted higher effects than individual indicators.</p><p><strong>Conclusion: </strong>The rate of change in metabolic and diffusion parameters on interim PET/CT can predict the prognosis of patients with DLBCL.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"411"},"PeriodicalIF":2.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of long-term trends and 15-year predictions of smoking-related bladder cancer burden in china across different age and sex groups from 1990 to 2021.","authors":"Jieming Zuo, Junhao Chen, Zhiyong Tan, Xingcheng Zhu, Haifeng Wang, Shi Fu, Jiansong Wang","doi":"10.1007/s12672-025-02157-3","DOIUrl":"10.1007/s12672-025-02157-3","url":null,"abstract":"<p><strong>Background: </strong>Tobacco is a significant risk factor for bladder cancer, with notable disparities in smoking rates and cancer prevalence between sex. Our objective is to assess the sex- and age-specific burden of bladder cancer attributable to smoking in China from 1990 to 2021, and predict its future trends over the next 15 years using GBD study data.</p><p><strong>Methods: </strong>All data were extracted from the 2021 GBD study, utilizing metrics such as mortality rates, disability-adjusted life years (DALYs), age-standardized mortality rates (ASMR), and age-standardized DALY rates (ASDR) to describe the burden of smoking-attributable bladder cancer in China. We employed joinpoint and age-period-cohort (APC) analysis methods to elucidate the epidemiological characteristics of bladder cancer. Frontier analysis was used to visually demonstrate the potential for burden reduction based on the development level of each country or region. We applied the ARIMA model to fit and predict the future burden of smoking-attributable bladder cancer in China for the next 15 years.</p><p><strong>Results: </strong>From 1990 to 2021, the number of deaths and DALYs due to smoking-attributable bladder cancer in China significantly increased. However, ASMR and ASDR decreased for both sexs but males experiencing a higher burden. Population aging drove the decline in ASMR and ASDR, despite rising absolute deaths and DALYs. Joinpoint regression yielded average annual percentage changes (AAPC) of - 1.23 for ASMR and - 1.38 for ASDR, with the rate of change being lower in males than in females. The impact of age, period, and cohort on mortality rates varied. There was a slight increase in relative health inequality in the bladder cancer burden among countries of different income levels. By 2036, ASDR and ASMR for smoking-related bladder cancer in China are expected to continue decreasing, with this trend being more pronounced in males.</p><p><strong>Conclusion: </strong>Over the past three decades, the number of deaths and DALYs due to smoking-related bladder cancer in China has significantly increased across different sexs and age groups, while ASMR and ASDR have shown a declining trend, reflecting certain public health progress. This trend is especially evident among males and is primarily driven by population aging and demographic effects. The inequality among countries of different income levels has slightly increased. The burden of smoking-related bladder cancer in China is projected to continue declining by 2036, particularly among males. Therefore, precise prevention and intervention strategies targeting different sexs and age groups are essential to further alleviate the public health burden of smoking-related bladder cancer.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"408"},"PeriodicalIF":2.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematically investigate the mechanism underlying the therapeutic effect of emodin in treatment of prostate cancer.","authors":"Gang Yuan, Jingxin Mao, Zheng Li","doi":"10.1007/s12672-025-02141-x","DOIUrl":"10.1007/s12672-025-02141-x","url":null,"abstract":"<p><strong>Objective: </strong>To systematically investigate the mechanism underlying the therapeutic effect of emodin in treatment of prostate cancer.</p><p><strong>Methods: </strong>Combine network pharmacology, molecular docking, molecular dynamics and experimental verification to explored the mechanism. Using the network pharmacology method, through the TCMSP, DisGeNET and Genecards database, the corresponding targets and related signaling pathways of emodin were screened, and emodin and core targets were studied by molecular docking and molecular dynamics uasing Cytoscape 3.7.2 and other software. The biological processes, cellular components and molecular functions of the key targets were determined by GO enrichment analysis. KEGG enrichment analysis identified signaling pathways associated with key targets. GEPIA and Kaplan-Meier database were used to determine the relationship between the expression of core genes in normal people and prostate cancer patients and the prognosis of patients. Cell proliferation inhibition experiment was carried out by MTT method. The mRNA and protein levels of CASP3, TNF, IL1B, TP53, PPARG, and MYC in PC-3 cells were evaluated by RT-PCR and WB method respectively.</p><p><strong>Results: </strong>There were 31 common targets which closely related to emodin in the treatment of prostate cancer. PPI network analysis showed that MYC, PPARG, TP53, TNF, CASP3, IL1B were the core targets. Go and KEGG enrichment analysis showed that pathways in cancer and IL-17 signaling pathway were the key pathways. Molecular docking and molecular dynamics results indicated that emodin had good binding to prostate cancer and 6 core proteins, and the binding force with TP53 protein was the strongest and most stable. The expression of CASP3 protein in normal people was stronger than that in patients with prostate cancer, and the expression of TP53 protein was closely related to the survival rate of patients with prostate cancer. Experimental verification result revealed that EM significantly increased mRNA expressions of CASP3, PPARG and decreased protein expressions of TNF, TP53, MYC at concentrations ranging from 0.1 to 1.6 μmol/L. Emodin significantly increased protein expressions of CASP3, PPARG and decreased protein expressions of TNF, TP53, MYC, IL1B at concentrations ranging from 10 to 160 µmol/L.</p><p><strong>Conclusion: </strong>Emodin and TP53 have the best binding and stable conformation among core genes. Emodin exhibits a significant inhibitory effect on PC-3 cells at concentration 0.4 ~ 1.6 μmol/L. It showed that anti-prostate cancer properties by regulating cancer and 1L-17 signaling pathway through up-regulating the expressions of CASP3, PPARG genes/proteins, down-regulating IL1B, TP53, TNF, MYC genes/proteins.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"413"},"PeriodicalIF":2.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of tumor immune infiltration-associated VPS72 and prognostic significance of VPS72 and CD8A in hepatocellular carcinoma.","authors":"Zhou Yang, Xiao Feng, Haoyuan Yu, Lei Lv, Chengli Gao, Wei Liu, Shuhong Yi, Changchang Jia, Binsheng Fu","doi":"10.1007/s12672-025-02017-0","DOIUrl":"10.1007/s12672-025-02017-0","url":null,"abstract":"<p><strong>Background: </strong>Copy Number Alterations (CNAs)-driven genes have gained attention as potential markers for predicting the response to immune checkpoint blockade in cancer treatment. Among them, VPS72 has emerged as a promising candidate in hepatocellular carcinoma (HCC). However, the relationship between VPS72 and immune infiltration remains unclear.</p><p><strong>Methods: </strong>TIMER analysis was performed to identify immune populations in bulk-RNAseq data. Then, we investigated the relationship between VPS72 and immune infiltration in HCC using diverse data sources, including the TCGA and GEO databases, clinical specimens, and animal models.</p><p><strong>Results: </strong>Our findings in the immunogenomic and TCGA-LIHC studies revealed significant enrichment of VPS72 among IRG in the altered group. Differential analysis and KEGG pathway analysis further highlighted the involvement of differentially expressed genes (DETs) in pathways related to the T cell receptor signaling pathway. Importantly, TIMER analysis suggested that low expression of VPS72 was associated with high infiltration of CD8 + T cells in multiple publicly available HCC datasets. To validate these findings, we conducted in vivo experiments and observed higher CD8A expression in VPS72-knockdown tumors. Additionally, in our patient cohort, individuals with low VPS72 expression exhibited higher CD8A expression. Furthermore, we identified a co-expression subtype characterized by low VPS72 and high CD8A levels, which showed a more favorable disease-free survival outcome in HCC.</p><p><strong>Conclusions: </strong>The expression of VPS72 in tumors is associated with the tumor infiltration. VPS72 and CD8A coexpression are prognostic biomarkers in HCC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"410"},"PeriodicalIF":2.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progress of immune senescence in multiple myeloma treatment resistance.","authors":"Yanan Jia, Lixiang Yan, Chenyang Fan, Hui Sun, Xinli Zhou, Zhexin Shi","doi":"10.1007/s12672-025-02136-8","DOIUrl":"10.1007/s12672-025-02136-8","url":null,"abstract":"<p><p>Multiple myeloma has become the second most common hematologic malignancy threatening human health with the increasing incidence in the population, and the emergence of drug resistance in its treatment has become a problem that needs to be solved urgently. Recent studies have shown that the immune system is closely related to the development of multiple myeloma, and immune senescence plays an extremely critical role in MM treatment resistance. In this paper, we review the connection between immune senescence and the development of MM and its possible role in the drug resistance of MM treatment, to provide new research ideas for the in-depth study of the mechanism of immune senescence and the search for new immunotherapeutic targets to overcome the phenomenon of drug resistance in the immunotherapy of MM patients.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"402"},"PeriodicalIF":2.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}