BMC Cancer最新文献

{"title":"NFKBIE as a prognostic biomarker and therapeutic target for GBM: role in Hedgehog signaling activation.","authors":"Feng Mo, Yang Li, Ce Dong, Lijun Yang, Xiaoli Ma, Baogen Pan, Zhenzeng Fan","doi":"10.1186/s12885-025-14775-9","DOIUrl":"10.1186/s12885-025-14775-9","url":null,"abstract":"<p><p>Glioblastoma (GBM), as one of the most common and aggressive primary brain tumors, pose significant challenges in diagnosis and treatment, highlighting the urgent need for the identification of novel biomarkers, NFKBIE, which may play a critical role in tumor progression, immune modulation, and therapeutic response. We investigated the role of NFKBIE in GBM through both bioinformatics analysis and experimental validation. Initially, bioinformatics analysis based on public databases revealed significant differential expression of NFKBIE across various cancer types, particularly in GBM, where elevated expression was correlated with poor patient prognosis, including overall survival, disease-specific survival, and progression-free survival. Furthermore, genetic alterations in NFKBIE, such as copy number variations (CNVs) and tumor mutational burden (TMB), were significantly associated with tumor progression. In the experimental validation phase, we utilized small interfering RNA (siRNA) technology to silence NFKBIE expression in GBM cell lines, including U87 and T98G. Functional assays were then performed to assess the impact of NFKBIE knockdown. Cell proliferation assays, including CCK-8 and clonogenic assays, demonstrated that silencing NFKBIE significantly inhibited the proliferation of GBM cells. Migration and invasion assays, including wound healing and Transwell assays, further confirmed that NFKBIE knockdown markedly suppressed the migratory and invasive abilities of GBM cells. Additionally, apoptosis assays, such as TUNEL staining, revealed that NFKBIE silencing significantly promoted apoptosis in GBM cells. Western blot analysis confirmed the changes in the expression of key markers associated with proliferation, stemness, migration, invasion, and apoptosis. Furthermore, in a mouse xenograft model, NFKBIE knockdown significantly slowed tumor growth. Histological analysis of the excised tumors confirmed that reduced NFKBIE expression was closely associated with the inhibition of tumor growth. Notably, NFKBIE silencing also led to the downregulation of components of the Hedgehog signaling pathway, suggesting that NFKBIE may regulate tumor progression through modulation of this critical pathway. In conclusion, high NFKBIE expression is strongly associated with GBM progression and poor prognosis, and targeting its expression may offer a promising therapeutic strategy for GBM treatment.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"1512"},"PeriodicalIF":3.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral blood multimodal integration via cross-attention for cancer immune profiling.","authors":"Xiong Li, Yi Hua, Hongwei Liu, Juan Zhou, Yuejin Zhang, Haowen Chen","doi":"10.1186/s12885-025-14969-1","DOIUrl":"10.1186/s12885-025-14969-1","url":null,"abstract":"<p><strong>Objective: </strong>Accurate cancer risk prediction is hindered by complex, multi-layered immune interactions, and traditional tissue biopsies are invasive and lack scalability for large-scale or repeated assessments. Peripheral blood offers a minimally invasive and accessible alternative for immune profiling. This study aims to develop CAMFormer, a deep learning framework that integrates multimodal peripheral blood-derived immune features for precise, non-invasive early cancer risk prediction.</p><p><strong>Methods: </strong>CAMFormer combines mRNA expression, immune cell frequencies, and TCR diversity index, leveraging a cross-attention-based multimodal Transformer to capture cross-scale immune interactions.</p><p><strong>Results: </strong>In five-fold cross-validation, CAMFormer achieved an AUC of 0.92 and an F1-score of 0.85 on the validation set, outperforming unimodal and baseline methods.</p><p><strong>Conclusion: </strong>These results highlight the potential benefits of integrating multimodal immune features with cross-attention mechanisms for early cancer detection and for guiding future personalized immunotherapy studies.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"1523"},"PeriodicalIF":3.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AI-Driven predictive modeling of cervical intraepithelial neoplasia severity: a comprehensive analysis with clinical adoption frameworks.","authors":"Farah Farzaneh, Amir Soltani, Fatemeh Dastyar, Marzieh Mohammadi, Maryam Sadat Hosseini","doi":"10.1186/s12885-025-14974-4","DOIUrl":"10.1186/s12885-025-14974-4","url":null,"abstract":"","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"1521"},"PeriodicalIF":3.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting hematologic toxicity in advanced cervical cancer patients using interpretable machine learning models based on radiomics and dosimetrics.","authors":"Jun Zhu, Qionghui Zhou, Luqiao Chen, Zhipeng He, Jianfeng Tan, Jinmeng Pang, Qianxi Ni","doi":"10.1186/s12885-025-14999-9","DOIUrl":"10.1186/s12885-025-14999-9","url":null,"abstract":"<p><strong>Background and objectives: </strong>Hematologic toxicity (HT) is a common and serious side effect for advanced cervical cancer patients undergoing chemoradiotherapy. Accurately predicting HT can significantly improve patient management and treatment outcomes. This study aims to develop and evaluate interpretable machine learning models that use radiomic and dosimetric features to predict HT in advanced cervical cancer patients.</p><p><strong>Methods and materials: </strong>Retrospectively collected general clinical data, planning CT images, and dose files from 205 patients with advanced cervical cancer who underwent chemoradiotherapy, and classified them according to the severity of HT. Radiomics and dosiomics features were extracted from the same region of interest, and feature selection was performed using a random forest algorithm. Radiomics models, dosiomics models, and hybrid models were then constructed based on extreme gradient boosting trees. Sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) were calculated to evaluate the classification performance of the models. Finally, SHAP values were used to perform interpretability analysis on the best model to enhance the transparency and practicality of the model.</p><p><strong>Results: </strong>The sensitivity, specificity, and AUC values for the radiomics model were 0.42, 0.86, and 0.78, respectively, while those for the dosiomics model were 0.50, 0.90, and 0.74. In contrast, the hybrid model exhibited superior classification performance with sensitivity, specificity, and AUC values of 0.50, 0.83, and 0.83, respectively. Compared to the standalone radiomics and dosiomics models, the hybrid model demonstrated enhanced classification capability. Interpretability analysis based on SHAP values not only provided a ranking of feature importance and the distribution of feature impacts on model outputs but also elucidated the specific decision-making processes influenced by these features and the interactions between them. This enables clinicians to gain a more intuitive understanding of the model's decisions.</p><p><strong>Conclusions: </strong>For patients with advanced cervical cancer undergoing chemoradiotherapy, the integration of radiomics and dosiomics features can significantly enhance the classification performance of predictive models, thereby holding considerable potential for refining patient treatment strategies. Interpretability analysis based on SHAP values can aid clinicians in more readily understanding the model's decisions, thus promoting the effective implementation of the model in clinical practice.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"1516"},"PeriodicalIF":3.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Berberine: a promising strategy to combat cetuximab-resistance in colorectal cancer.","authors":"Jianmin Ye, Bingchan Sun, Fengmei Xia, Guoxin Wang, Huimin Liu, Jianghua Ding, Mingfu Tong","doi":"10.1186/s12885-025-15013-y","DOIUrl":"10.1186/s12885-025-15013-y","url":null,"abstract":"<p><p>Cetuximab, a monoclonal antibody against epidermal growth factor receptor (EGFR), is approved as a front-line treatment for metastatic colorectal cancers, but limited efficacy is obtained. Combinatory therapy is a potentially promising strategy to enhance anticancer effects, overcome drug resistance and improve overall clinical survival. Here, we show that berberine combined with cetuximab created a synergistic inhibitory effect on cetuximab-resistant CRC cells in vitro and in vivo. Human phospho-kinase assay explored that the phosphorylation of Src and Chk-2 was inhibited by berberine and decreased greatly when combined with cetuximab. Adding KX2-391 (Src inhibitor) rather than BML-277 (Chk-2 inhibitor) with cetuximab resulted in more cell death and apoptosis. Conversely, activation of Src with MLR-1023 mitigated the inhibitory effect of berberine alone or in combination with cetuximab. Additionally, the activities of downstream kinases of Src such as mTOR, STAT3 and the production of ROS were inhibited greatly by berberine plus cetuximab. Taken together, we concluded that the synergistic effects of BBR and cetuximab may be mediated by decreasing the activities of Src/mTOR/STAT3 and the production of ROS, thus inducing greater extent of apoptosis in cancer cells.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"1520"},"PeriodicalIF":3.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ACOXL-AS1's pan-cancer dynamics and its proliferative impact on endometrial endometrioid carcinoma.","authors":"Hongrong Wu, Ruilin Lin, Liangli Hong","doi":"10.1186/s12885-025-15005-y","DOIUrl":"10.1186/s12885-025-15005-y","url":null,"abstract":"<p><strong>Background: </strong>Long non-coding RNAs (lncRNAs) are critically involved in carcinogenesis; however, the pan-cancer significance and functional mechanisms of ACOXL-AS1 remain largely uncharacterized. This study comprehensively investigates the expression landscape, prognostic value, and biological impact of ACOXL-AS1 across multiple malignancies, with a specific focus on its pro-proliferative role in endometrial endometrioid carcinoma (EEC).</p><p><strong>Methods: </strong>We analyzed ACOXL-AS1 expression and its association with clinical outcomes using pan-cancer RNA-seq data from TCGA and GTEx databases. Functional validation was performed in EEC cell lines (HHUA, HEC-1 A) via lentivirus-mediated overexpression, followed by CCK-8, colony formation, and transwell migration/invasion assays. Mechanistic insights were investigated using integrated bioinformatics approaches.</p><p><strong>Results: </strong>ACOXL-AS1 was significantly downregulated in most cancers, and higher expression correlated with improved prognosis. Elevated ACOXL-AS1 levels were associated with smaller tumor size, lower disease stage, reduced metastasis, and decreased tumor mutational burden (TMB)/microsatellite instability (MSI). It also modulated the immunosuppressive tumor microenvironment. Critically, ACOXL-AS1 overexpression significantly inhibited EEC cell proliferation, migration, invasion, and tumor growth in xenograft models. Mechanistically, it may regulate RPA4 expression through the homologous recombination pathway in EEC cells.</p><p><strong>Conclusions: </strong>ACOXL-AS1 may play a role as a tumor suppressor in endometrial endometrioid carcinoma (EEC), suggesting its potential as a prognostic biomarker and a candidate for further exploration as a therapeutic target.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"1522"},"PeriodicalIF":3.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of molecular profiles (Nectin-4 and TROP-2) in upper tract urothelial carcinoma with a positive history of urinary bladder cancer vs. UTUC only in the era of ADCs.","authors":"Mohammed Rafea Kanaan, Jessica Schmitz, Jan Hinrich Braesen, Markus Antonius Kuczyk, Hossein Tezval","doi":"10.1186/s12885-025-15042-7","DOIUrl":"10.1186/s12885-025-15042-7","url":null,"abstract":"<p><p>Upper tract urothelial carcinoma (UTUC) and urinary bladder cancer (UBC), though histologically similar, differ molecularly, prompting interest in their biomarker profiles for targeted therapies like antibody-drug conjugates (ADCs) enfortumab vedotin (targeting Nectin-4) and sacituzumab govitecan (targeting TROP-2). This study investigated Nectin-4 and TROP-2 expression in 87 UTUC patients, including 54 with a history of concurrent UBC (UTUC + UBC) and 33 with UTUC alone. Immunohistochemical analysis revealed widespread TROP-2 expression (98.8% of samples), with high levels linked to low-grade UTUC (p = 0.043) and intense staining (mean H-score 227 ± 63) across both cohorts. Nectin-4 was expressed in 70.1% of samples overall but was more frequent in the UTUC + UBC group (88.8% vs. 63.6% in UTUC-only patients), though this difference lacked statistical significance (p = 0.340). Notably, Nectin-4 staining intensity was weak in both groups (mean H-score 66 ± 65), suggesting biological distinctions between UTUC with and without UBC. The findings imply that ADCs targeting TROP-2 and Nectin-4 may hold therapeutic promise in UTUC without requiring prior biomarker testing. Additionally, the elevated Nectin-4 expression in UTUC + UBC patients hints at divergent molecular pathways that could influence treatment strategies, warranting further clinical exploration.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"1525"},"PeriodicalIF":3.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vismodegib treatment in locally advanced basal cell carcinoma limited to the facial region: a single-center experience.","authors":"İvo Gökmen, Erdem Şen","doi":"10.1186/s12885-025-14914-2","DOIUrl":"10.1186/s12885-025-14914-2","url":null,"abstract":"<p><strong>Introduction: </strong>Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer. Treatment typically begins with surgical intervention. However, in cases of locally advanced and metastatic BCC (laBCC and mBCC), Hedgehog signaling pathway inhibitors such as sonidegib and vismodegib are used.</p><p><strong>Materials and methods: </strong>This retrospective study included 28 adult patients with laBCC who were treated with 150 mg daily oral vismodegib at Mehmet Akif Ersoy State Hospital between 2018 and 2023. Patients were monitored until disease progression, intolerable side effects, or treatment discontinuation. Treatment efficacy was evaluated using objective response rate (ORR) and disease control rate (DCR). Safety was assessed based on adverse events (AEs) reported in accordance with the CTCAE v. 5.0 classification. Statistical analyses, including overall survival (OS) and progression-free survival (PFS), were performed and analyzed using SPSS version 25.</p><p><strong>Results: </strong>The overall ORR was 89.3%, with 39.3% of patients achieving complete response (CR). The median PFS was 15.1 months, and the median OS was 37.5 months. Female gender and prior surgical interventions were identified as independent prognostic factors for PFS, while ECOG-PS score and the duration of vismodegib exposure were significant predictors of OS. AEs were reported in 78.6% of patients, with dysgeusia and muscle spasms being the most prevalent. Grade 3 or 4 toxicity occurred in 14.5% of patients, and 13% (n = 3) discontinued treatment due to AEs. Patients receiving treatment for ≥ 12 months experienced a higher incidence of AEs (92.9%) compared to those treated for < 12 months (64.3%).</p><p><strong>Conclusion: </strong>Vismodegib demonstrated high efficacy in treating patients with laBCC, with a significant proportion achieving CR. However, long-term treatment was associated with an increased incidence of AEs, highlighting the need for careful monitoring of safety in prolonged therapies.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"1514"},"PeriodicalIF":3.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in Sentinel lymph node biopsy outcomes and prognosis between HER2-low and HER2-zero breast cancer.","authors":"Koji Takada, Shinichiro Kashiwagi, Mariko Nishikawa, Asuka Kochi, Chika Watanabe, Haruhito Kinoshita, Kana Ogisawa, Masatsune Shibutani, Tamami Morisaki","doi":"10.1186/s12885-025-14970-8","DOIUrl":"10.1186/s12885-025-14970-8","url":null,"abstract":"","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"1518"},"PeriodicalIF":3.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High sodium intake: a silent killer driving global gastric cancer burden.","authors":"Xiqiang Zhang, Zhaoyi Jing, Ao Yu, Xinzhen Xu, Hua Meng, Kexin Wang","doi":"10.1186/s12885-025-14891-6","DOIUrl":"10.1186/s12885-025-14891-6","url":null,"abstract":"<p><strong>Background: </strong>High sodium intake is a recognized risk factor for increased gastric cancer mortality. This study examines the trends and distribution of stomach cancer burden associated with high sodium intake from 1990 to 2021, with a focus on its relationship with age, period, and birth cohort.</p><p><strong>Methods: </strong>Utilizing data from the 2021 Global Burden of Disease study, we applied an age-period-cohort model to conduct statistical analysis. We calculated age, period, and cohort effects, as well as net drift (overall annual percentage change), for gastric cancer deaths and disability-adjusted life years (DALYs) associated with high sodium intake across 204 countries and regions.</p><p><strong>Results: </strong>In 2021, 7.93% of global gastric cancer deaths and 7.92% of DALYs were linked to high sodium intake. Populations in East Asia and those with a high-middle Sociodemographic Index (SDI) bore the heaviest burden. Over the 32-year period, the global age-standardized mortality rate [Net drift = -2.33(95%CI:-2.37 to -2.28)] and age-standardized DALYs rate [Net drift = -2.56(95%CI:-2.65 to -2.47)] generally demonstrated a declining trend, particularly in high SDI regions [Net drift =-2.91 (95%CI: -3.02 to -2.81)]. China, as a representative country, exhibited unfavorable age, period, and cohort effects. Future projections suggest further declines in mortality and DALYs numbers, along with corresponding age-standardized rates.</p><p><strong>Conclusion: </strong>Despite ongoing global efforts to reduce sodium intake, gastric cancer remains a significant public health challenge, especially in East Asia. The findings underscore the necessity of developing targeted prevention strategies for high-risk groups, such as the elderly and males, to mitigate the global burden of gastric cancer.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"1517"},"PeriodicalIF":3.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}