Pub Date : 2025-12-15DOI: 10.1186/s12885-025-15420-1
Hai Zeng, Yan-Ling Wu, Xiaofeng Wang, Hui Bai, Cihui Yan, Wencheng Zhang, Qifeng Wang
Purpose: To evaluate the efficacy and safety of systemic treatment combined with radiotherapy (RT) as the first-line treatment for de novo advanced esophageal cancer (EC).
Methods: A meta-analysis was conducted, and it followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. A literature search was performed systematically in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science on February 1, 2025. The protocol of this meta-analysis was published in PROSPERO with the registration number CRD42025650118.
Results: Eight studies involving a total of 11,356 patients were finally included. Systemic treatment combined with RT improved OS (HR = 0.72, 95% CI: 0.70-0.74, P < 0.001) and PFS (HR = 0.70, 95% CI: 0.62-0.78, P < 0.001) compared with systemic treatment alone. The grade ≥ 3 treatment-related lymphopenia (OR = 5.52, P < 0.001), leukopenia (OR = 1.56, P < 0.001), and esophagitis (OR = 13.11, P < 0.001) were more frequent in the RT-combined group; no significant differences were observed in other severe toxicities. Subgroup analysis on systemic treatment type, ESCC, and TNM stage edition also demonstrated that this RT-combined treatment could provide significant survival benefits. Exploratory analysis showed that maximal survival benefit emerged in patients who received systemic therapy, especially immunochemotherapy, combined with radical (≥ 50 Gy) primary tumor RT.
Conclusions: By synthesizing data from both the pre-immunotherapy and immunotherapy eras involving 11,356 patients, we found that the incorporation of radical radiotherapy into first-line systemic treatment regimens improves survival outcomes while maintaining acceptable toxicity profiles in selected patients with advanced EC.Further randomized clinical trials are needed to verify our conclusions.
目的:评价全身治疗联合放疗(RT)作为新发晚期食管癌(EC)一线治疗的疗效和安全性。方法:进行meta分析,并遵循系统评价和meta分析首选报告项目(PRISMA)指南。在2025年2月1日系统地检索PubMed、EMBASE、Cochrane Central Register of Controlled Trials和Web of Science。该荟萃分析的方案发表在PROSPERO杂志上,注册号为CRD42025650118。结果:最终纳入8项研究,共11356例患者。结论:通过综合11356例患者免疫治疗前和免疫治疗时期的数据,我们发现,在选定的晚期EC患者中,将根治性放疗纳入一线全身治疗方案可改善生存结果,同时保持可接受的毒性特征。需要进一步的随机临床试验来验证我们的结论。
{"title":"Efficacy and safety of radiotherapy in first-line treatment for de novo advanced esophageal cancer in the era of immunochemotherapy: a systematic review and meta-analysis.","authors":"Hai Zeng, Yan-Ling Wu, Xiaofeng Wang, Hui Bai, Cihui Yan, Wencheng Zhang, Qifeng Wang","doi":"10.1186/s12885-025-15420-1","DOIUrl":"https://doi.org/10.1186/s12885-025-15420-1","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the efficacy and safety of systemic treatment combined with radiotherapy (RT) as the first-line treatment for de novo advanced esophageal cancer (EC).</p><p><strong>Methods: </strong>A meta-analysis was conducted, and it followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. A literature search was performed systematically in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science on February 1, 2025. The protocol of this meta-analysis was published in PROSPERO with the registration number CRD42025650118.</p><p><strong>Results: </strong>Eight studies involving a total of 11,356 patients were finally included. Systemic treatment combined with RT improved OS (HR = 0.72, 95% CI: 0.70-0.74, P < 0.001) and PFS (HR = 0.70, 95% CI: 0.62-0.78, P < 0.001) compared with systemic treatment alone. The grade ≥ 3 treatment-related lymphopenia (OR = 5.52, P < 0.001), leukopenia (OR = 1.56, P < 0.001), and esophagitis (OR = 13.11, P < 0.001) were more frequent in the RT-combined group; no significant differences were observed in other severe toxicities. Subgroup analysis on systemic treatment type, ESCC, and TNM stage edition also demonstrated that this RT-combined treatment could provide significant survival benefits. Exploratory analysis showed that maximal survival benefit emerged in patients who received systemic therapy, especially immunochemotherapy, combined with radical (≥ 50 Gy) primary tumor RT.</p><p><strong>Conclusions: </strong>By synthesizing data from both the pre-immunotherapy and immunotherapy eras involving 11,356 patients, we found that the incorporation of radical radiotherapy into first-line systemic treatment regimens improves survival outcomes while maintaining acceptable toxicity profiles in selected patients with advanced EC.Further randomized clinical trials are needed to verify our conclusions.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15DOI: 10.1186/s12885-025-15334-y
Shima Soleimani Sardou, Mohammad Mehdi Ghaemi, Fatemeh Sadat Rezvaninejad, Abolfazl Seyrfar, Arash Shahravan, Nader Navabi, Raziyehsadat Rezvaninejad
Background: Oral cancer remains a major global health issue, with timely diagnosis being essential due to its varied clinical presentation. This study explores how artificial intelligence (AI) can support early detection by analyzing intraoral photographs.
Methods: A cross-sectional analysis was performed using 518 intraoral clinical images collected from the Department of Oral Medicine, Kerman Faculty of Dentistry, between 2009 and 2023. The dataset comprised 104 images of malignant lesions and 414 of benign or normal tissue, all confirmed by a specialist in oral pathology. Three pretrained deep learning models, DenseNet-121, EfficientNet-B0, and ResNet-50, were evaluated for their ability to classify lesions as malignant or benign. The data were split into training (80%) and testing (20%) sets, with preprocessing completed before analysis.
Results: Among the models, DenseNet-121 demonstrated superior performance, achieving 91% accuracy, 75% sensitivity, 98% specificity, 75% positive predictive value, 96% negative predictive value, an F1 score of 84%, and an area under the curve of 90%. These results exceeded the diagnostic accuracy of an experienced oral specialist.
Conclusion: AI-based analysis of clinical images can significantly improve early oral cancer detection and should be integrated into clinical workflows to enhance diagnostic precision.
{"title":"\"Enhancing early detection of oral cancer: a comparative study of artificial intelligence models and clinical specialist in lesion classification\".","authors":"Shima Soleimani Sardou, Mohammad Mehdi Ghaemi, Fatemeh Sadat Rezvaninejad, Abolfazl Seyrfar, Arash Shahravan, Nader Navabi, Raziyehsadat Rezvaninejad","doi":"10.1186/s12885-025-15334-y","DOIUrl":"https://doi.org/10.1186/s12885-025-15334-y","url":null,"abstract":"<p><strong>Background: </strong>Oral cancer remains a major global health issue, with timely diagnosis being essential due to its varied clinical presentation. This study explores how artificial intelligence (AI) can support early detection by analyzing intraoral photographs.</p><p><strong>Methods: </strong>A cross-sectional analysis was performed using 518 intraoral clinical images collected from the Department of Oral Medicine, Kerman Faculty of Dentistry, between 2009 and 2023. The dataset comprised 104 images of malignant lesions and 414 of benign or normal tissue, all confirmed by a specialist in oral pathology. Three pretrained deep learning models, DenseNet-121, EfficientNet-B0, and ResNet-50, were evaluated for their ability to classify lesions as malignant or benign. The data were split into training (80%) and testing (20%) sets, with preprocessing completed before analysis.</p><p><strong>Results: </strong>Among the models, DenseNet-121 demonstrated superior performance, achieving 91% accuracy, 75% sensitivity, 98% specificity, 75% positive predictive value, 96% negative predictive value, an F1 score of 84%, and an area under the curve of 90%. These results exceeded the diagnostic accuracy of an experienced oral specialist.</p><p><strong>Conclusion: </strong>AI-based analysis of clinical images can significantly improve early oral cancer detection and should be integrated into clinical workflows to enhance diagnostic precision.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Inflammatory blood markers and tumor-infiltrating lymphocytes (TILs) are associated with the prognosis of various cancers. However, reports on their value as prognostic markers in soft tissue undifferentiated pleomorphic sarcoma (UPS) are limited. We aimed to clarify the predictive value of these markers for the prognosis of patients with UPS, focusing on resectable tumors of the extremities and trunk.
Methods: This retrospective analysis included data from 103 patients with localized UPS in the extremities and trunk. The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and systemic inflammatory response index (SIRI) were calculated, and the median values were determined as cut-off values. Immunohistochemical staining of CD8 + TILs was also performed. Disease-specific overall survival (DOS) and distant metastasis-free survival (DMFS) rates were analyzed using the Kaplan-Meier method, and prognostic factors were identified using the Cox proportional hazards model.
Results: Among the inflammatory blood markers, SIRI was found to be a sensitive prognostic factor, and a high SIRI was associated with worse DOS (P = 0.16) and DMFS (P = 0.09). Although CD8 + TILs were not associated with DOS (P = 0.67), high CD8 + TILs correlated with improved DMFS (P = 0.20). Only tumor size > 10 cm was significantly associated with worse DMFS (P = 0.02) in the univariate analysis, while inflammatory blood markers and CD8 + TIL showed no correlation. The combination of SIRI and CD8 + TILs revealed that high CD8 + TILs in tumor tissue could improve DMFS (P = 0.04) and DOS (P = 0.15) in patients with high SIRI compared to those with low CD8 + TILs and high SIRI.
Conclusions: In patients with localized UPS, CD8 + TILs infiltration into the tumor tissue could improve the prognosis of patients with high SIRI.
{"title":"The prognostic value of systemic inflammatory response index (SIRI) and CD8 + tumor-infiltrating lymphocytes for patients with localized undifferentiated pleomorphic sarcoma of soft tissue.","authors":"Hiroshi Kobayashi, Hiroyuki Abe, Tetsuo Ushiku, Yutaka Nezu, Toru Hiruma, Shintaro Iwata, Akira Kawai, Tomoaki Mori, Robert Nakayama, Naohiro Makise, Tsukasa Yonemoto, Sakae Tanaka","doi":"10.1186/s12885-025-15182-w","DOIUrl":"10.1186/s12885-025-15182-w","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory blood markers and tumor-infiltrating lymphocytes (TILs) are associated with the prognosis of various cancers. However, reports on their value as prognostic markers in soft tissue undifferentiated pleomorphic sarcoma (UPS) are limited. We aimed to clarify the predictive value of these markers for the prognosis of patients with UPS, focusing on resectable tumors of the extremities and trunk.</p><p><strong>Methods: </strong>This retrospective analysis included data from 103 patients with localized UPS in the extremities and trunk. The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and systemic inflammatory response index (SIRI) were calculated, and the median values were determined as cut-off values. Immunohistochemical staining of CD8 + TILs was also performed. Disease-specific overall survival (DOS) and distant metastasis-free survival (DMFS) rates were analyzed using the Kaplan-Meier method, and prognostic factors were identified using the Cox proportional hazards model.</p><p><strong>Results: </strong>Among the inflammatory blood markers, SIRI was found to be a sensitive prognostic factor, and a high SIRI was associated with worse DOS (P = 0.16) and DMFS (P = 0.09). Although CD8 + TILs were not associated with DOS (P = 0.67), high CD8 + TILs correlated with improved DMFS (P = 0.20). Only tumor size > 10 cm was significantly associated with worse DMFS (P = 0.02) in the univariate analysis, while inflammatory blood markers and CD8 + TIL showed no correlation. The combination of SIRI and CD8 + TILs revealed that high CD8 + TILs in tumor tissue could improve DMFS (P = 0.04) and DOS (P = 0.15) in patients with high SIRI compared to those with low CD8 + TILs and high SIRI.</p><p><strong>Conclusions: </strong>In patients with localized UPS, CD8 + TILs infiltration into the tumor tissue could improve the prognosis of patients with high SIRI.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"1870"},"PeriodicalIF":3.4,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12707010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762402","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}
Pub Date : 2025-12-15DOI: 10.1186/s12885-025-15240-3
Esra Zeynelgil, Engin Eren Kavak, İsmail Dilli, Özlem Aydın İsak, Doğan Yazılıtaş, Gökşen İnanç İmamoğlu, Ömer Bayır
Objective: This study aimed to evaluate the clinical and laboratory factors affecting treatment response and treatment tolerance in patients diagnosed with head and neck squamous cell carcinoma (HNSCC) and treated with chemoradiotherapy (CRT) after three cycles of induction chemotherapy.
Method: Patients who were followed up in the oncology clinic between January 2014 and December 2024 and who could not undergo an organ-sparing approach or surgery were analyzed retrospectively. Demographic, clinical, biochemical and inflammatory parameters of the patients were examined. Binary-logistic regression analysis was used for patients who could not complete the treatment due to toxicity, Cox-regression analysis was used to investigate the factors affecting overall survival (OS), and Roc-curve analysis was used to determine the ideal-cut-off values for blood markers.
Results: A total of 92 patients with HNSCC were included in the study. In univariate logistic regression analysis, age ≥ 60 (p = 0.006), presence of comorbidity (p = 0.029), body mass index (BMI) < 23.25 (p = 0.005), poor ECOG performance score (2-3) (p < 0.001) and low prognostic nutritional index (PNI) (p = 0.011) were found to be significant risk factors for not completing treatment. Multivariate logistic regression of age, BMI, ECOG, and PNI together formed a predictive model for treatment incompletion. In Cox regression analysis, BMI <23.25 (p=0.016), poor ECOG performance score (2-3) (p=0.002), advanced disease stage (p=0.002), and low PNI (<51.1) (p=0.006) were the main risk factors for unfavorable overall survival. Gender, smoking, tumor location, treatment regimen, and hematological parameters had no significant effect on survival and treatment completion.
Conclusion: In HNSCC patients who underwent post-induction CRT, nutritional parameters such as BMI and PNI and performance status play a determining role on treatment tolerance and survival. Detailed assessment of nutritional status before treatment may have an impact on treatment success and survival.
{"title":"BMI and PNI as predictors of treatment completion and survival in locally advanced HNSCC receiving sequential chemoradiotherapy.","authors":"Esra Zeynelgil, Engin Eren Kavak, İsmail Dilli, Özlem Aydın İsak, Doğan Yazılıtaş, Gökşen İnanç İmamoğlu, Ömer Bayır","doi":"10.1186/s12885-025-15240-3","DOIUrl":"10.1186/s12885-025-15240-3","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to evaluate the clinical and laboratory factors affecting treatment response and treatment tolerance in patients diagnosed with head and neck squamous cell carcinoma (HNSCC) and treated with chemoradiotherapy (CRT) after three cycles of induction chemotherapy.</p><p><strong>Method: </strong>Patients who were followed up in the oncology clinic between January 2014 and December 2024 and who could not undergo an organ-sparing approach or surgery were analyzed retrospectively. Demographic, clinical, biochemical and inflammatory parameters of the patients were examined. Binary-logistic regression analysis was used for patients who could not complete the treatment due to toxicity, Cox-regression analysis was used to investigate the factors affecting overall survival (OS), and Roc-curve analysis was used to determine the ideal-cut-off values for blood markers.</p><p><strong>Results: </strong>A total of 92 patients with HNSCC were included in the study. In univariate logistic regression analysis, age ≥ 60 (p = 0.006), presence of comorbidity (p = 0.029), body mass index (BMI) < 23.25 (p = 0.005), poor ECOG performance score (2-3) (p < 0.001) and low prognostic nutritional index (PNI) (p = 0.011) were found to be significant risk factors for not completing treatment. Multivariate logistic regression of age, BMI, ECOG, and PNI together formed a predictive model for treatment incompletion. In Cox regression analysis, BMI <23.25 (p=0.016), poor ECOG performance score (2-3) (p=0.002), advanced disease stage (p=0.002), and low PNI (<51.1) (p=0.006) were the main risk factors for unfavorable overall survival. Gender, smoking, tumor location, treatment regimen, and hematological parameters had no significant effect on survival and treatment completion.</p><p><strong>Conclusion: </strong>In HNSCC patients who underwent post-induction CRT, nutritional parameters such as BMI and PNI and performance status play a determining role on treatment tolerance and survival. Detailed assessment of nutritional status before treatment may have an impact on treatment success and survival.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"1869"},"PeriodicalIF":3.4,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12706939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762422","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}
Pub Date : 2025-12-15DOI: 10.1186/s12885-025-15443-8
Hui Xie, Jianfang Zhang, Qing Li, Tao Tan
This study explores the non-invasive prediction of MKI-67 (Ki67) expression status in breast cancer using preoperative ultrasound image heterogeneity. Data from 432 patients (training set) and 109 (test set) across two medical institutions were analyzed. Tumor regions were automatically outlined using the Swin-unet network, and habitat clustering within these regions was performed using the k-means method. Radiomics and deep learning features (ResNet-101) were extracted from both global tumor regions and habitat subregions. Laboratory data were integrated, followed by the Least Absolute Shrinkage and Selection Operator (LASSO) feature reduction and machine learning modeling to predict Ki67 expression status. Model performance was evaluated using accuracy (Acc), area under the curve (AUC) with 95% confidence intervals (CI), sensitivity (Sen), specificity (Spe), positive predictive value (PPV), negative predictive value (NPV), calibration curves, confusion matrices, and decision curves. The DeLong test was used to compare the diagnostic performance of the composite model with individual models. The results showed that the combined model (Habitat + Global + Laboratory + Deep Learning) achieved the best predictive performance, with Acc, AUC, Sen, Spe, PPV, and NPV of 0.798, 0.838, 0.780, 0.809, 0.711, and 0.859, respectively, in the test set. Calibration curves and confusion matrices confirmed the model's robustness, while decision curves demonstrated its clinical utility. The DeLong test confirmed the composite model's significantly superior AUC compared to several individual models, though not all combined models showed significant differences. However, despite not showing significant advantages in comparisons with some combined models, the composite model, leveraging its unique strength of comprehensively integrating multi-dimensional features, has demonstrated stronger adaptability and stability in real-world clinical application scenarios, providing more reliable support for accurate prediction. In conclusion, preoperative ultrasound image heterogeneity, through the integration of habitat subregion, global tumor, laboratory, and deep learning features, provides valuable insights for predicting Ki67 expression status in breast cancer, enhancing routine preoperative ultrasonography and offering a potential non-invasive method for preoperative Ki67 prediction.
本研究探讨了术前超声图像异质性对乳腺癌中MKI-67 (Ki67)表达状态的无创预测。来自两家医疗机构的432名患者(训练集)和109名患者(测试集)的数据进行了分析。使用swan -unet网络自动勾画肿瘤区域,并使用k-means方法在这些区域内进行生境聚类。放射组学和深度学习特征(ResNet-101)分别从全球肿瘤区域和栖息地亚区域提取。整合实验室数据,然后使用最小绝对收缩和选择算子(LASSO)特征约简和机器学习建模来预测Ki67的表达状态。通过准确性(Acc)、曲线下面积(AUC)(95%置信区间CI)、敏感性(Sen)、特异性(Spe)、阳性预测值(PPV)、阴性预测值(NPV)、校准曲线、混淆矩阵和决策曲线来评估模型的性能。采用DeLong检验比较复合模型与单个模型的诊断性能。结果表明,组合模型(Habitat + Global + Laboratory + Deep Learning)的预测效果最好,测试集的Acc、AUC、Sen、Spe、PPV和NPV分别为0.798、0.838、0.780、0.809、0.711和0.859。校正曲线和混淆矩阵证实了模型的稳健性,而决策曲线则证明了模型的临床实用性。DeLong试验证实,复合模型的AUC明显优于几个单独的模型,但并非所有的组合模型都存在显著差异。然而,尽管与某些组合模型相比,复合模型并没有显示出明显的优势,但复合模型凭借其综合整合多维特征的独特优势,在实际临床应用场景中表现出更强的适应性和稳定性,为准确预测提供了更可靠的支持。综上所述,术前超声图像异质性通过整合栖息地分区域、整体肿瘤、实验室和深度学习特征,为预测Ki67在乳腺癌中的表达状况提供了有价值的见解,增强了术前常规超声检查,并为术前Ki67预测提供了一种潜在的无创方法。
{"title":"Enhancing breast cancer diagnosis: non-invasive prediction of MKI-67 (Ki67) expression using ultrasound images.","authors":"Hui Xie, Jianfang Zhang, Qing Li, Tao Tan","doi":"10.1186/s12885-025-15443-8","DOIUrl":"https://doi.org/10.1186/s12885-025-15443-8","url":null,"abstract":"<p><p>This study explores the non-invasive prediction of MKI-67 (Ki67) expression status in breast cancer using preoperative ultrasound image heterogeneity. Data from 432 patients (training set) and 109 (test set) across two medical institutions were analyzed. Tumor regions were automatically outlined using the Swin-unet network, and habitat clustering within these regions was performed using the k-means method. Radiomics and deep learning features (ResNet-101) were extracted from both global tumor regions and habitat subregions. Laboratory data were integrated, followed by the Least Absolute Shrinkage and Selection Operator (LASSO) feature reduction and machine learning modeling to predict Ki67 expression status. Model performance was evaluated using accuracy (Acc), area under the curve (AUC) with 95% confidence intervals (CI), sensitivity (Sen), specificity (Spe), positive predictive value (PPV), negative predictive value (NPV), calibration curves, confusion matrices, and decision curves. The DeLong test was used to compare the diagnostic performance of the composite model with individual models. The results showed that the combined model (Habitat + Global + Laboratory + Deep Learning) achieved the best predictive performance, with Acc, AUC, Sen, Spe, PPV, and NPV of 0.798, 0.838, 0.780, 0.809, 0.711, and 0.859, respectively, in the test set. Calibration curves and confusion matrices confirmed the model's robustness, while decision curves demonstrated its clinical utility. The DeLong test confirmed the composite model's significantly superior AUC compared to several individual models, though not all combined models showed significant differences. However, despite not showing significant advantages in comparisons with some combined models, the composite model, leveraging its unique strength of comprehensively integrating multi-dimensional features, has demonstrated stronger adaptability and stability in real-world clinical application scenarios, providing more reliable support for accurate prediction. In conclusion, preoperative ultrasound image heterogeneity, through the integration of habitat subregion, global tumor, laboratory, and deep learning features, provides valuable insights for predicting Ki67 expression status in breast cancer, enhancing routine preoperative ultrasonography and offering a potential non-invasive method for preoperative Ki67 prediction.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145761542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15DOI: 10.1186/s12885-025-15230-5
Chan Zhang, Lei Li, Yanxiu Liu, Bo Yu, Jing Liu, Shujing Li
<p><strong>Introduction: </strong>Papillary thyroid carcinoma (PTC) is a significant type of endocrine cancer, characterized by diverse genetic alterations and a complex molecular environment. Extracellular vesicles (EVs), especially those derived from mesenchymal stem cells (MSCs), have emerged as promising targeted drug carriers for cancer cells. Additionally, reprogramming MSC-derived EVs represents a novel strategy for cancer gene therapy, offering potential solutions to clinical challenges and new treatment directions. Increasing evidence suggests that MSC-derived EVs play a crucial role in tumor progression by delivering circular RNAs (circRNAs), which function as microRNA (miRNA) sponges. However, the underlying molecular mechanisms and their clinical applications remain to be fully explored and validated.</p><p><strong>Methods and results: </strong>Through in-depth mining using high-throughput bioinformatics analyses, we conducted a comprehensive differential gene analysis between PTC tissues and normal thyroid tissues, successfully identifying circ-0000258 as a key regulatory molecule. Following multi-dimensional validation in PTC cell lines and clinical specimens, the consistent low expression of circ-0000258 was confirmed, strongly suggesting its latent potential as a tumor suppressor. Functional mechanistic investigations have revealed that overexpression of circ-0000258 potently curbs the malignant biological behaviors of PTC cells, notably inhibiting cell proliferation and invasion. More significantly, circ-0000258 acts as a molecular sponge, specifically sequestering miR-146b. This action relieves the post-transcriptional repression of p53 by miR-146b, thereby activating the p53-mediated apoptotic signaling cascade. By intervening at the genetic regulatory level, circ-0000258 effectively reprograms the fate of thyroid tumor cells. Furthermore, in the context of translational medicine research, we innovatively constructed an engineered delivery platform based on extracellular vesicles derived from human umbilical cord mesenchymal stem cells (hUCMSC-EVs). By exogenously loading circ-0000258 into these vesicles, we successfully endowed these natural nanocarriers with targeted anti-cancer properties. Both in vitro and in vivo functional assays demonstrated that the engineered hUCMSC-EVs loaded with circ-0000258 could effectively act on PTC cells, significantly reducing the volume of xenograft tumors and inducing tumor cell apoptosis. Notably, when combined with cisplatin, these engineered extracellular vesicles exhibited a synergistic anti-cancer effect, suggesting their potential to overcome chemoresistance in thyroid tumors.</p><p><strong>Conclusion: </strong>This study has established the circ-0000258/miR-146b/p53 regulatory axis as a crucial mechanism underlying tumor suppression in PTC. It has also demonstrated the translational potential of hUCMSC-EVs as a safe and efficient delivery vehicle. By integrating the functional role of
{"title":"Engineered hUCMSC-derived extracellular vesicles deliver circ-0000258 to restore p53-mediated tumor suppression in papillary thyroid carcinoma.","authors":"Chan Zhang, Lei Li, Yanxiu Liu, Bo Yu, Jing Liu, Shujing Li","doi":"10.1186/s12885-025-15230-5","DOIUrl":"10.1186/s12885-025-15230-5","url":null,"abstract":"<p><strong>Introduction: </strong>Papillary thyroid carcinoma (PTC) is a significant type of endocrine cancer, characterized by diverse genetic alterations and a complex molecular environment. Extracellular vesicles (EVs), especially those derived from mesenchymal stem cells (MSCs), have emerged as promising targeted drug carriers for cancer cells. Additionally, reprogramming MSC-derived EVs represents a novel strategy for cancer gene therapy, offering potential solutions to clinical challenges and new treatment directions. Increasing evidence suggests that MSC-derived EVs play a crucial role in tumor progression by delivering circular RNAs (circRNAs), which function as microRNA (miRNA) sponges. However, the underlying molecular mechanisms and their clinical applications remain to be fully explored and validated.</p><p><strong>Methods and results: </strong>Through in-depth mining using high-throughput bioinformatics analyses, we conducted a comprehensive differential gene analysis between PTC tissues and normal thyroid tissues, successfully identifying circ-0000258 as a key regulatory molecule. Following multi-dimensional validation in PTC cell lines and clinical specimens, the consistent low expression of circ-0000258 was confirmed, strongly suggesting its latent potential as a tumor suppressor. Functional mechanistic investigations have revealed that overexpression of circ-0000258 potently curbs the malignant biological behaviors of PTC cells, notably inhibiting cell proliferation and invasion. More significantly, circ-0000258 acts as a molecular sponge, specifically sequestering miR-146b. This action relieves the post-transcriptional repression of p53 by miR-146b, thereby activating the p53-mediated apoptotic signaling cascade. By intervening at the genetic regulatory level, circ-0000258 effectively reprograms the fate of thyroid tumor cells. Furthermore, in the context of translational medicine research, we innovatively constructed an engineered delivery platform based on extracellular vesicles derived from human umbilical cord mesenchymal stem cells (hUCMSC-EVs). By exogenously loading circ-0000258 into these vesicles, we successfully endowed these natural nanocarriers with targeted anti-cancer properties. Both in vitro and in vivo functional assays demonstrated that the engineered hUCMSC-EVs loaded with circ-0000258 could effectively act on PTC cells, significantly reducing the volume of xenograft tumors and inducing tumor cell apoptosis. Notably, when combined with cisplatin, these engineered extracellular vesicles exhibited a synergistic anti-cancer effect, suggesting their potential to overcome chemoresistance in thyroid tumors.</p><p><strong>Conclusion: </strong>This study has established the circ-0000258/miR-146b/p53 regulatory axis as a crucial mechanism underlying tumor suppression in PTC. It has also demonstrated the translational potential of hUCMSC-EVs as a safe and efficient delivery vehicle. By integrating the functional role of","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"1868"},"PeriodicalIF":3.4,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12706891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762387","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}
Background: Immune checkpoint inhibitors (ICIs) improve the outcomes across solid tumours, although they can cause severe immune-related adverse events (irAEs). Due to this possibility of side effects, practical and low-cost predictors of severe irAEs are needed to guide patient monitoring and care.
Methods: We conducted a single-centre retrospective cohort study involving 593 patients who were treated with anti-PD-1/PD-L1 monotherapy or anti-PD-1/PD-L1 plus anti-CTLA-4 combination therapy from June 2016 to November 2024. The primary endpoint was the time to the first severe irAE (grade ≥ 3). Peripheral blood biomarkers were evaluated at baseline and immediately before the cycle 3. The cumulative incidence was estimated, and the associations were quantified using the Fine-Gray subdistribution hazards ratio (sHR) model in a competing risks framework.
Results: Overall, 11.6% of patients experienced a severe irAE, with the median time to the first event being 12 weeks and the most frequent severe irAE being colitis (n = 21; 3.5%). Combination therapy was associated with a higher risk when compared with monotherapy (sHR 3.71, 95% confidence interval [CI] 2.25-6.13). Baseline eosinophils > 250/µL were associated with an increased risk (sHR 2.22, 95% CI 1.35-3.65). A lower red cell distribution width (RDW) was likewise associated with the risk at two timepoints: baseline RDW ≤ 15.8% (sHR 2.60, 95% CI 1.35-5.01) and pre-cycle 3 RDW ≤ 14.3% (sHR 2.71, 95% CI 1.44-5.09). The effects were directionally consistent across subgroups, and no interactions were detected. The other blood biomarkers tested were not significant (all p > 0.05).
Conclusions: A high baseline eosinophil count and a lower RDW early on during therapy identify patients at increased risk of severe irAEs. These accessible measures could support personalised monitoring and biomarker-guided patient selection. However, external validation is needed to confirm the robustness and validate the thresholds identified in this study prior to clinical use.
背景:免疫检查点抑制剂(ICIs)改善了实体肿瘤的预后,尽管它们可能导致严重的免疫相关不良事件(irAEs)。由于这种副作用的可能性,需要实用和低成本的严重irae预测方法来指导患者的监测和护理。方法:2016年6月至2024年11月,我们对593例接受抗pd -1/PD-L1单药治疗或抗pd -1/PD-L1 +抗ctla -4联合治疗的患者进行了单中心回顾性队列研究。主要终点是发生首次严重irAE(≥3级)的时间。在基线和第3周期前评估外周血生物标志物。估计累积发病率,并在竞争风险框架下使用Fine-Gray亚分布风险比(sHR)模型对关联进行量化。结果:总体而言,11.6%的患者经历了严重的irAE,到第一次事件的中位时间为12周,最常见的严重irAE是结肠炎(n = 21; 3.5%)。与单药治疗相比,联合治疗与更高的风险相关(sHR 3.71, 95%可信区间[CI] 2.25-6.13)。基线嗜酸性粒细胞bb0 250/µL与风险增加相关(sHR 2.22, 95% CI 1.35-3.65)。较低的红细胞分布宽度(RDW)同样与两个时间点的风险相关:基线RDW≤15.8% (sHR 2.60, 95% CI 1.35-5.01)和周期前3 RDW≤14.3% (sHR 2.71, 95% CI 1.44-5.09)。这些效应在各个亚组之间方向一致,没有发现相互作用。其他血液标志物检测结果均无统计学意义(p < 0.05)。结论:在治疗早期,较高的基线嗜酸性粒细胞计数和较低的RDW可识别严重irae风险增加的患者。这些可获得的措施可以支持个性化监测和生物标志物引导的患者选择。然而,在临床使用之前,需要外部验证来确认稳健性和验证本研究中确定的阈值。
{"title":"Using routine blood tests to predict severe immune-related adverse events during immune checkpoint inhibitor treatment.","authors":"Caner Acar, Fatma Pinar Açar, Gökhan Şahin, Haydar Çağatay Yüksel, Burçak Karaca, Erdem Göker","doi":"10.1186/s12885-025-15460-7","DOIUrl":"https://doi.org/10.1186/s12885-025-15460-7","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) improve the outcomes across solid tumours, although they can cause severe immune-related adverse events (irAEs). Due to this possibility of side effects, practical and low-cost predictors of severe irAEs are needed to guide patient monitoring and care.</p><p><strong>Methods: </strong>We conducted a single-centre retrospective cohort study involving 593 patients who were treated with anti-PD-1/PD-L1 monotherapy or anti-PD-1/PD-L1 plus anti-CTLA-4 combination therapy from June 2016 to November 2024. The primary endpoint was the time to the first severe irAE (grade ≥ 3). Peripheral blood biomarkers were evaluated at baseline and immediately before the cycle 3. The cumulative incidence was estimated, and the associations were quantified using the Fine-Gray subdistribution hazards ratio (sHR) model in a competing risks framework.</p><p><strong>Results: </strong>Overall, 11.6% of patients experienced a severe irAE, with the median time to the first event being 12 weeks and the most frequent severe irAE being colitis (n = 21; 3.5%). Combination therapy was associated with a higher risk when compared with monotherapy (sHR 3.71, 95% confidence interval [CI] 2.25-6.13). Baseline eosinophils > 250/µL were associated with an increased risk (sHR 2.22, 95% CI 1.35-3.65). A lower red cell distribution width (RDW) was likewise associated with the risk at two timepoints: baseline RDW ≤ 15.8% (sHR 2.60, 95% CI 1.35-5.01) and pre-cycle 3 RDW ≤ 14.3% (sHR 2.71, 95% CI 1.44-5.09). The effects were directionally consistent across subgroups, and no interactions were detected. The other blood biomarkers tested were not significant (all p > 0.05).</p><p><strong>Conclusions: </strong>A high baseline eosinophil count and a lower RDW early on during therapy identify patients at increased risk of severe irAEs. These accessible measures could support personalised monitoring and biomarker-guided patient selection. However, external validation is needed to confirm the robustness and validate the thresholds identified in this study prior to clinical use.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-13DOI: 10.1186/s12885-025-15454-5
Xingxing Jiang, Yongping Gui, Yu Yang, Jie Li, Aijun Liang
Background: Glioma is the most common primary malignant tumor of the central nervous system and is associated with an extremely poor prognosis. Given its highly complex molecular landscape, there is an urgent need to identify novel diagnostic biomarkers. This study systematically identified core glioma genes through multi-cohort integration and single-cell analysis.
Methods: Five Gene Expression Omnibus (GEO) transcriptomic datasets (GSE109857, GSE15824, GSE35158, GSE4290, and GSE90886; 504 samples) were integrated, and batch effects were corrected using ComBat. Differentially expressed genes (DEGs) were identified and combined with weighted gene co-expression network analysis (WGCNA) to obtain candidate modules. Feature genes were further screened using multiple approaches, including CytoHubba, least absolute shrinkage and selection operator (LASSO) regression, support vector machine-recursive feature elimination (SVM-RFE), and random forest (RF) analysis. Validation was performed using external GEO datasets, receiver operating characteristic (ROC) analysis, and quantitative real-time polymerase chain reaction (qRT-PCR) based on 69 clinical samples. Additional analyses included gene set enrichment analysis (GSEA), CIBERSORT-based immune infiltration profiling, expression mapping across three single-cell RNA sequencing (scRNA-seq) datasets (GSE273274, GSE162631, and GSE182109), and construction of competing endogenous RNA (ceRNA) and transcription factor (TF) networks, as well as drug enrichment analysis.
Results: A total of 409 glioma-related candidate genes were identified. Six hub genes, SYP, SYN1, RAB3A, SLC17A7, SYN2, and STXBP1, were consistently identified across all algorithms. All six genes were significantly downregulated in glioma, as confirmed by GEO datasets (area under the curve [AUC]: 0.787-0.802) and clinical qRT-PCR validation. GSEA revealed that low expression of these genes was associated with activation of the cell cycle, complement and coagulation cascades, and immune dysregulation. Immune infiltration analysis showed negative correlations with M1/M2 macrophages and activated natural killer (NK) cells. Single-cell analyses indicated that these hub genes were primarily enriched in tumor-propagating cell (TPC)-like tumor cells but were markedly reduced in glioma core regions. Competing endogenous RNA (ceRNA)/TF networks and drug enrichment analyses suggested multilayered regulatory mechanisms and associations with neurotransmitter-related compounds.
Conclusion: The six identified hub genes are consistently downregulated in glioma and exhibit strong diagnostic potential. Their close association with the immune microenvironment and tumor-cell lineage highlights their value as biomarkers and potential therapeutic targets.
{"title":"Integrative bulk and single-cell transcriptomic profiling identifies core gene networks and potential therapeutic targets in glioma.","authors":"Xingxing Jiang, Yongping Gui, Yu Yang, Jie Li, Aijun Liang","doi":"10.1186/s12885-025-15454-5","DOIUrl":"https://doi.org/10.1186/s12885-025-15454-5","url":null,"abstract":"<p><strong>Background: </strong>Glioma is the most common primary malignant tumor of the central nervous system and is associated with an extremely poor prognosis. Given its highly complex molecular landscape, there is an urgent need to identify novel diagnostic biomarkers. This study systematically identified core glioma genes through multi-cohort integration and single-cell analysis.</p><p><strong>Methods: </strong>Five Gene Expression Omnibus (GEO) transcriptomic datasets (GSE109857, GSE15824, GSE35158, GSE4290, and GSE90886; 504 samples) were integrated, and batch effects were corrected using ComBat. Differentially expressed genes (DEGs) were identified and combined with weighted gene co-expression network analysis (WGCNA) to obtain candidate modules. Feature genes were further screened using multiple approaches, including CytoHubba, least absolute shrinkage and selection operator (LASSO) regression, support vector machine-recursive feature elimination (SVM-RFE), and random forest (RF) analysis. Validation was performed using external GEO datasets, receiver operating characteristic (ROC) analysis, and quantitative real-time polymerase chain reaction (qRT-PCR) based on 69 clinical samples. Additional analyses included gene set enrichment analysis (GSEA), CIBERSORT-based immune infiltration profiling, expression mapping across three single-cell RNA sequencing (scRNA-seq) datasets (GSE273274, GSE162631, and GSE182109), and construction of competing endogenous RNA (ceRNA) and transcription factor (TF) networks, as well as drug enrichment analysis.</p><p><strong>Results: </strong>A total of 409 glioma-related candidate genes were identified. Six hub genes, SYP, SYN1, RAB3A, SLC17A7, SYN2, and STXBP1, were consistently identified across all algorithms. All six genes were significantly downregulated in glioma, as confirmed by GEO datasets (area under the curve [AUC]: 0.787-0.802) and clinical qRT-PCR validation. GSEA revealed that low expression of these genes was associated with activation of the cell cycle, complement and coagulation cascades, and immune dysregulation. Immune infiltration analysis showed negative correlations with M1/M2 macrophages and activated natural killer (NK) cells. Single-cell analyses indicated that these hub genes were primarily enriched in tumor-propagating cell (TPC)-like tumor cells but were markedly reduced in glioma core regions. Competing endogenous RNA (ceRNA)/TF networks and drug enrichment analyses suggested multilayered regulatory mechanisms and associations with neurotransmitter-related compounds.</p><p><strong>Conclusion: </strong>The six identified hub genes are consistently downregulated in glioma and exhibit strong diagnostic potential. Their close association with the immune microenvironment and tumor-cell lineage highlights their value as biomarkers and potential therapeutic targets.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}