Discover. Oncology最新文献

{"title":"Identification and characterization of lLF2 as a prognostic biomarker in HER2-positive breast cancer using Mendelian randomization and machine learning.","authors":"Xiyun Quan, Yi Deng, Meiyuan Huang, Huimei Yi, Ming Li","doi":"10.1007/s12672-025-03762-y","DOIUrl":"10.1007/s12672-025-03762-y","url":null,"abstract":"<p><strong>Background: </strong>HER2-positive breast cancer is an aggressive molecular subtype characterized by high recurrence rates and poor prognosis. Identifying robust biomarkers for prognosis and therapeutic response is essential to improve individualized treatment strategies.</p><p><strong>Methods: </strong>Based on genome-wide association study (GWAS) data, summary data-based Mendelian randomization (SMR) analysis was used to screen disease-related genes. The diagnostic model of HER2-positive breast cancer was constructed by combining LASSO, random forest and SVM-RFE and the characteristic genes were identified. The prognostic correlation was evaluated through Kaplan-Meier analysis. The SNP association, expression level, immune activity and drug sensitivity of ILF2 were analyzed emphatically. H&E staining and immunohistochemistry were used to verify the expression of ILF2 in tumor tissues.</p><p><strong>Results: </strong>A total of 14 genes associated with HER2-positive breast cancer were identified through SMR analysis, with the most significant SNPs enriched on chromosome 1. Integrating three machine learning algorithms (LASSO, Random Forest, and SVM-RFE), four robust diagnostic feature genes were identified: SLC16A3, ILF2, ARRDC3, and SNAPIN. Among them, ILF2 emerged as a key gene of interest. Kaplan-Meier survival analysis revealed that high expression of ILF2, NEK10, LAMTOR5, and APOBEC3A was significantly associated with poorer prognosis. The top ILF2-associated SNP (rs10908848) showed a strong negative regulatory effect on disease risk. Further functional analyses indicated that high ILF2 expression was associated with suppressed antitumor immune activity and reduced sensitivity to multiple chemotherapeutic agents, suggesting its role in immune evasion and therapy resistance. Immunohistochemical staining confirmed significantly upregulated ILF2 protein expression in HER2-positive breast tumor tissues compared with adjacent normal tissues.</p><p><strong>Conclusion: </strong>ILF2 is biologically and clinically important in HER2-positive breast cancer, and its high expression is linked with tumor immune escape and increased resistance to chemotherapeutic agents. Future studies should further explore the mechanism and application of ILF2 as a potential therapeutic target.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1940"},"PeriodicalIF":2.9,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336540","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":"Log odds of negative lymph nodes/T stage as a novel predictor of post-resection outcome in non-small cell lung cancer patients.","authors":"Liu Shao, Haoyang Cao, Hao Yang, Dongmei Li","doi":"10.1007/s12672-025-03801-8","DOIUrl":"10.1007/s12672-025-03801-8","url":null,"abstract":"<p><strong>Background: </strong>Surgery with systematic lymph node (LN) dissection remains the primary treatment for early-stage and locally advanced operable non-small-cell lung cancer (NSCLC). However, the effect of the log odds of negative lymph nodes/T stage (LONT) in NSCLC remains unclear. This study aims to evaluate the correlation between LONT and prognosis of stage I-III NSCLC patients who underwent resection.</p><p><strong>Methods: </strong>Clinical data from patients who underwent NSCLC resection were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The log odds of negative LONT, defined as log(NLNs + 1)/T stage, was calculated for each patient. The nonlinear relationship between LONT and overall survival (OS) and lung cancer-specific survival (LCSS) was evaluated using the cubic spline smoothing technique and Cox regression. The optimal LONT cut-off point was determined using X-tile plots, and propensity score matching (PSM) was performed to minimize inter-group differences.</p><p><strong>Results: </strong>LONT demonstrated a nonlinear positive relationship with both OS and LCSS. Based on X-tile plot-determined cut-off point of 0.60, participants were categorized into low (< 0.60) and high (≥ 0.60) LONT subgroups. Both before and after PSM, the high LONT group exhibited significantly better OS and LCSS compared to the low LONT group (both P < 0.001). Similar survival differences were observed in subgroup analyses based on lymph node status and TNM stage. LONT was an independent predictor of OS (HR: 0.78, 95% CI: 0.74-0.81, P < 0.001) and LCSS (HR: 0.75, 95% CI: 0.71-0.78, P < 0.001).</p><p><strong>Conclusions: </strong>LONT is a novel robust prognostic factor that could complement TNM staging system. A higher LONT is associated with better survival in stage I-III NSCLC patients who received resection.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1922"},"PeriodicalIF":2.9,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328285","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":"High VCP/p97 expression associates with low PD-L1 TPS in oropharyngeal squamous cell carcinoma.","authors":"Inga Marte Charlott Seuthe, Markus Ruwe, Franz Mitze, Steffi Silling, Eric Ehrke-Schulz, Sabine Eichhorn, Jonas Jae-Hyun Park","doi":"10.1007/s12672-025-03839-8","DOIUrl":"10.1007/s12672-025-03839-8","url":null,"abstract":"","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1923"},"PeriodicalIF":2.9,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328327","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":"Thymoquinone-conjugated liposomes improve cytotoxic and proapoptotic effects against hepatocellular cancer by altering the EGFR/ERK/MEK signaling axis.","authors":"Shaymaa A Abdulmalek, Fatma A Mahmoud, Doaa Awad, Abdulrahman M Saleh, Ayman I Elkady, Doaa A Ghareeb, Mahmoud Balbaa","doi":"10.1007/s12672-025-03714-6","DOIUrl":"10.1007/s12672-025-03714-6","url":null,"abstract":"<p><p>Modulating the signaling axis between tumors and their environment is one of the key strategies to slow down the progression of hepatocellular carcinoma (HCC). In this study, we aimed to design a polyethylene glycolated liposome loaded with thymoquinone (PEG-TQ-LP) as a delivery system to investigate its effect on HCC progression and the underlying mechanisms in vitro and in vivo. The study revealed the inhibitory effects of PEG-TQ-LP on the proliferation of HCC cells and facilitated apoptosis. The observed effect can be explained by the increased expression of BAX and the decreased expression of BCL2. The activation of p38-MAPK has been implicated in the anti-oncogenic impact of PEG-TQ-LP. This activation was correlated with the dephosphorylation of MEK and ERK. The in vivo study confirmed that PEG-TQ-LP reduces the detrimental effects of free TQ on liver tissue, suppresses tumor growth, and reestablishes the oxidative state equilibrium. Molecular docking analysis demonstrated that TQ docked well with three key targets. The findings from current investigations may represent a novel strategy for the treatment of liver cancer, as PEG-TQ-LP potently promotes apoptosis. This is achieved via thymoquinone's ability to bind to cancer protein targets' active sites, which indicates that it functions similarly to anticancer medications.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1924"},"PeriodicalIF":2.9,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328392","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":"Observation of the impact of applying the fast track surgery concept during the perioperative period of breast-conserving surgery for breast cancer on the effectiveness of patient care and complications.","authors":"Yu-Ting Li, Zhong-Ru Cao","doi":"10.1007/s12672-025-03827-y","DOIUrl":"10.1007/s12672-025-03827-y","url":null,"abstract":"<p><strong>Objective: </strong>To observe the impact of applying the fast track surgery (FTS) concept during the perioperative period of breast-conserving surgery for breast cancer on the effectiveness of patient care and the occurrence of complications.</p><p><strong>Methods: </strong>A retrospective analysis of clinical data was conducted for 92 cases of breast cancer patients admitted to our hospital from January 2022 to January 2023. All patients underwent breast-conserving surgery at our hospital and met the inclusion criteria. Patients were divided into two groups based on the different nursing interventions during the perioperative period: the control group (n = 46) received conventional nursing interventions, while the observation group (n = 46) received nursing interventions based on the fast track surgery concept. The nursing effectiveness, postoperative recovery, serum inflammatory factor levels, psychological negative emotions, and complication occurrence were compared between the two groups.</p><p><strong>Results: </strong>The overall nursing effectiveness rate in the control group was 80.43%, while it was 95.65% in the observation group, which was significantly higher than that in the control group (P<0.05). The observation group showed significantly shorter times for getting out of bed, drainage removal, initiation of oral intake, wound healing, and hospital stay, as well as lower levels of pain compared to the control group (P<0.05). Before intervention, there were no significant differences in IL-6, TNF-α, and NF-κB levels between the two groups (P>0.05). However, after intervention, the levels of IL-6, TNF-α, and NF-κB in the observation group were significantly lower than those in the control group (P<0.05). Before intervention, there were no significant differences in SAS and SDS scores between the two groups (P>0.05). However, after intervention, the SAS and SDS scores in the observation group were significantly lower than those in the control group (P<0.05). The complication rate in the control group was 23.91%, while it was 8.70% in the observation group, and the observation group had a significantly lower complication rate than the control group (P<0.05).</p><p><strong>Conclusion: </strong>The application of the fast track surgery concept during the perioperative period of breast-conserving surgery for breast cancer yields favorable results. Compared to conventional nursing interventions, fast track surgery concept-based nursing further enhances patient outcomes, improves the body's inflammatory response, and mitigates adverse emotions, thereby accelerating patient recovery and reducing the risk of surgery-related complications. This approach is worthy of clinical promotion.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1920"},"PeriodicalIF":2.9,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328352","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 analysis of KLHL35 expression and its prognostic value in cancer: implications for colorectal cancer diagnosis and therapy.","authors":"Rong Qin, Yiyao Duan, Shasha Bao, Hui Wang, Jing Zhou, Xirui Fan, Xiang Li, Guoyu Li, Jun Hu","doi":"10.1007/s12672-025-03715-5","DOIUrl":"10.1007/s12672-025-03715-5","url":null,"abstract":"","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1921"},"PeriodicalIF":2.9,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328317","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":"Immune cell dynamics and prognostic role of M2 macrophages and LDOC1 in colon adenocarcinoma.","authors":"Laibin Luo, Zhimin Xu, Hongwu Lin, Rong Huang","doi":"10.1007/s12672-025-03698-3","DOIUrl":"10.1007/s12672-025-03698-3","url":null,"abstract":"<p><strong>Background: </strong>Colon adenocarcinoma (COAD) is influenced by the tumor microenvironment, including immune cell dynamics, particularly M2 macrophages. Understanding these dynamics can offer insights into tumor progression and potential therapies.</p><p><strong>Methods: </strong>We analyzed TCGA COAD data to quantify immune infiltration using TIMER, CIBERSORT, QUANTISEQ, MCPcounter, xCell, and EPIC methods. The ESTIMATE algorithm provided stromal and immune scores. WGCNA identified key gene modules correlated with immune infiltration. Prognostic significance of these genes was assessed using univariate Cox regression, Kaplan-Meier analysis, and nomogram construction. Single-cell RNA sequencing data from TISCH2 was used to explore gene expression correlations across cell types. We also examined correlations of LDOC1 with TMB, MSI, NEO, and tumor purity, and predicted immunotherapy responses using TIDE and Submap analyses. Drug sensitivity was analyzed using GDSC data.</p><p><strong>Results: </strong>Significant variations in M2 macrophage levels were found between tumor and normal tissues. WGCNA identified three key gene modules. Univariate Cox regression highlighted DMPK and LDOC1 as significant prognostic genes. Pan-cancer analysis showed LDOC1 as a crucial prognostic marker across various cancers, with strong correlations to multiple pathways. Single-cell analysis revealed distinct expression patterns of DMPK and LDOC1. In COAD, LDOC1 expression correlated significantly with immune checkpoints and tumor microenvironment scores. TIDE and Submap analyses suggested better immunotherapy response in low LDOC1 groups. Drug sensitivity analysis identified eight potential therapeutic agents.</p><p><strong>Conclusion: </strong>This study underscores the importance of M2 macrophages and LDOC1 in COAD, highlighting their potential as prognostic markers and therapeutic targets, paving the way for personalized treatments.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1915"},"PeriodicalIF":2.9,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12534630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307182","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":"Mendelian randomization reveals contrasting effects of immune signaling molecules on bone and articular cartilage malignancies.","authors":"Haiying Huang, Yanshan Lin, Ming Xiang, Jiehui Fu","doi":"10.1007/s12672-025-03748-w","DOIUrl":"10.1007/s12672-025-03748-w","url":null,"abstract":"","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1916"},"PeriodicalIF":2.9,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12534676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307238","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":"Knowledge mapping and visualization of immune checkpoint inhibitor-related pneumonitis: a bibliometric analysis.","authors":"Yanyan Jiang, Mingling Xu, Shanlin Xu, Qian Wu","doi":"10.1007/s12672-025-03769-5","DOIUrl":"10.1007/s12672-025-03769-5","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) have shown significant effectiveness in cancer treatment, yet checkpoint inhibitor-related pneumonitis (CIP) remains a severe immune-related adverse event (irAE). This study conducts a bibliometric analysis to identify potential research directions for CIP associated with ICIs in cancer therapy.</p><p><strong>Methods: </strong>We retrieved articles published from 1991 to 2024 in the Web of Science Core Collection (WoSCC) database. Bibliometric tools, including VOSviewer, R-bibliometrix, and CiteSpace, were employed to analyze publication trends, contributing countries, journals, authors, and keywords.</p><p><strong>Results: </strong>A total of 673 publications were analyzed, with the United States, China, and Japan identified as the primary contributors. The Lancet Oncology was the leading journal in terms of article volume and impact factor. Jarushka Naidoo had the highest H-index and publication output among authors. Recent research has focused on enhancing ICI efficacy in lung cancer while minimizing safety risks associated with adverse events through various drug combinations and therapeutic modifications. Key areas of emphasis include expanding ICI applications beyond melanoma and non-small cell lung cancer (NSCLC), managing severe CIPs and pre-existing pulmonary conditions, integrating radiotherapy and chemoradiotherapy with immunotherapy, and exploring corticosteroids and immunosuppressants.</p><p><strong>Conclusion: </strong>Although the number of clinical trials on ICIs is increasing, effective strategies for preventing CIP and managing its symptoms are still lacking, and international collaboration in this research area is limited. This analysis offers a comprehensive overview of the current landscape, highlighting emerging research trends and key areas for future investigation.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1908"},"PeriodicalIF":2.9,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12534694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307237","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 effects of genetically determined plasma methyltransferases on digestive system cancers: a comprehensive bidirectional two-sample Mendelian randomization analysis.","authors":"Congcong Zhang, Xueying Li, Zhebin Dong, Yihui Weng, Weiming Yu, Xianlei Cai","doi":"10.1007/s12672-025-03758-8","DOIUrl":"10.1007/s12672-025-03758-8","url":null,"abstract":"<p><strong>Objectives: </strong>The causal relationship between plasma methyltransferase protein concentrations and the onset of digestive system cancers remains unclear. This study employed a Mendelian randomization (MR) analysis to explore potential causal relationships.</p><p><strong>Methods: </strong>A bidirectional two-sample MR analysis was conducted to systematically investigate causal associations. Data from the FinnGen Biobank and the European Bioinformatics Institute (EBI) were used for verification. This analysis focused on 14 types of methyltransferases and 5 types of digestive system cancers.</p><p><strong>Results: </strong>The analysis identified specific methyltransferases associated with increased risks for certain digestive system malignancies. Notably, dual verification confirmed that HEMK2 is associated with an increased risk of colorectal cancer [Odds Ratio (OR) = 1.28; 95% CI: 1.06-1.55 for FinnGen; OR = 1.18; 95% CI: 1.07-1.29 for EBI] and liver cancer (OR = 2.31; 95% CI: 1.29-4.14 for FinnGen; OR = 1.38; 95% CI: 1.08-1.76 for EBI). NTMT1 was also associated with colorectal cancer (OR = 1.16; 95% CI: 1.03-1.30 for FinnGen; OR = 1.10; 95% CI: 1.04-1.17 for EBI) and liver cancer (OR = 1.59; 95% CI: 1.11-2.27 for FinnGen; OR = 1.21;95%CI: 1.04-1.40 for EBI). We also found that some methyltransferases exhibit either harmful or protective effects in digestive system cancers; however, these findings have not been validated by another independent database. Therefore, the interpretation of these results requires caution.</p><p><strong>Conclusions: </strong>This study reveals that certain methyltransferases are associated with an increased risk of some digestive system cancers. HEMK2 and NTMT1 emerged as candidate genetically predicted biomarkers, meriting further research to elucidate their mechanistic functions and potential clinical applicability. Furthermore, as all genetic information in this study originates from European cohorts, the conclusions are primarily relevant to this population and necessitate validation in diverse ethnic groups.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1911"},"PeriodicalIF":2.9,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12534628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307305","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}