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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. 免疫化疗时代放疗一线治疗新发晚期食管癌的疗效和安全性:系统回顾和荟萃分析。
IF 3.4 2区 医学 Q2 ONCOLOGY Pub Date : 2025-12-15 DOI: 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。
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引用次数: 0
"Enhancing early detection of oral cancer: a comparative study of artificial intelligence models and clinical specialist in lesion classification". “提高口腔癌的早期发现:人工智能模型与临床专家病变分类的比较研究”。
IF 3.4 2区 医学 Q2 ONCOLOGY Pub Date : 2025-12-15 DOI: 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.

背景:口腔癌仍然是一个主要的全球健康问题,由于其多种临床表现,及时诊断至关重要。本研究探讨了人工智能(AI)如何通过分析口腔内照片来支持早期检测。方法:对2009 - 2023年克尔曼牙科学院口腔医学系518张口腔内临床影像进行横断面分析。该数据集包括104张恶性病变图像和414张良性或正常组织图像,均由口腔病理学专家确认。三个预训练的深度学习模型,DenseNet-121, EfficientNet-B0和ResNet-50,评估了它们将病变分类为恶性或良性的能力。数据分为训练集(80%)和测试集(20%),在分析之前完成预处理。结果:DenseNet-121的准确率为91%,灵敏度为75%,特异性为98%,阳性预测值为75%,阴性预测值为96%,F1评分为84%,曲线下面积为90%。这些结果超过了经验丰富的口腔专家的诊断准确性。结论:基于人工智能的临床影像分析可显著提高早期口腔癌的检出率,应融入临床工作流程,提高诊断准确率。
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引用次数: 0
The prognostic value of systemic inflammatory response index (SIRI) and CD8 + tumor-infiltrating lymphocytes for patients with localized undifferentiated pleomorphic sarcoma of soft tissue. 系统性炎症反应指数(SIRI)及CD8 +肿瘤浸润淋巴细胞对软组织局部未分化多形性肉瘤的预后价值
IF 3.4 2区 医学 Q2 ONCOLOGY Pub Date : 2025-12-15 DOI: 10.1186/s12885-025-15182-w
Hiroshi Kobayashi, Hiroyuki Abe, Tetsuo Ushiku, Yutaka Nezu, Toru Hiruma, Shintaro Iwata, Akira Kawai, Tomoaki Mori, Robert Nakayama, Naohiro Makise, Tsukasa Yonemoto, Sakae Tanaka

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.

背景:炎症性血液标志物和肿瘤浸润淋巴细胞(til)与多种癌症的预后有关。然而,关于其作为软组织未分化多形性肉瘤(UPS)预后标志物价值的报道有限。我们的目的是明确这些标志物对UPS患者预后的预测价值,重点是四肢和躯干的可切除肿瘤。方法:回顾性分析103例四肢和躯干局部UPS患者的资料。计算中性粒细胞-淋巴细胞比率(NLR)、血小板-淋巴细胞比率(PLR)、淋巴细胞-单核细胞比率(LMR)和全身炎症反应指数(SIRI),取中位数作为截止值。CD8 + TILs免疫组化染色。使用Kaplan-Meier方法分析疾病特异性总生存率(DOS)和远端无转移生存率(DMFS),并使用Cox比例风险模型确定预后因素。结果:在炎性血液标志物中,SIRI是一个敏感的预后因素,高SIRI与较差的DOS (P = 0.16)和DMFS (P = 0.09)相关。虽然CD8 + TILs与DOS无关(P = 0.67),但高CD8 + TILs与改善DMFS相关(P = 0.20)。在单因素分析中,只有肿瘤大小bbb10 cm与较差的DMFS显著相关(P = 0.02),而炎症血液标志物与CD8 + TIL无相关性。SIRI和CD8 + TILs联合应用发现,与低CD8 + TILs和高SIRI患者相比,高SIRI患者的肿瘤组织CD8 + TILs可改善DMFS (P = 0.04)和DOS (P = 0.15)。结论:在局限性UPS患者中,CD8 + TILs向肿瘤组织浸润可改善高SIRI患者的预后。
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引用次数: 0
BMI and PNI as predictors of treatment completion and survival in locally advanced HNSCC receiving sequential chemoradiotherapy. BMI和PNI作为局部晚期HNSCC接受序贯放化疗的治疗完成和生存的预测因子。
IF 3.4 2区 医学 Q2 ONCOLOGY Pub Date : 2025-12-15 DOI: 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.

目的:本研究旨在评价头颈部鳞状细胞癌(HNSCC)患者经3个周期诱导化疗后行放化疗(CRT)的临床和实验室因素对治疗反应和治疗耐受的影响。方法:回顾性分析2014年1月至2024年12月在肿瘤科门诊随访的不能行保留器官入路或手术的患者。检查患者的人口学、临床、生化及炎症指标。对因毒性导致无法完成治疗的患者采用二元logistic回归分析,对影响总生存期(OS)的因素采用cox回归分析,对血液标志物采用roc曲线分析确定理想截断值。结果:共有92例HNSCC患者纳入研究。单因素logistic回归分析中,年龄≥60岁(p = 0.006)、是否存在合并症(p = 0.029)、体重指数(BMI)。结论:接受诱导后CRT治疗的HNSCC患者,BMI、PNI等营养参数和运动状态对治疗耐受性和生存率起决定性作用。治疗前详细评估营养状况可能对治疗成功和生存有影响。
{"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}
引用次数: 0
Enhancing breast cancer diagnosis: non-invasive prediction of MKI-67 (Ki67) expression using ultrasound images. 增强乳腺癌诊断:利用超声图像无创预测MKI-67 (Ki67)表达。
IF 3.4 2区 医学 Q2 ONCOLOGY Pub Date : 2025-12-15 DOI: 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。
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引用次数: 0
Senescence-driven molecular subtyping in pancreatic cancer: a multi-omics framework for precision medicine. 胰腺癌中衰老驱动的分子分型:精准医学的多组学框架。
IF 3.4 2区 医学 Q2 ONCOLOGY Pub Date : 2025-12-15 DOI: 10.1186/s12885-025-15341-z
Meilong Shi, Penghao Li, Bo Li, Huan Wang, Xiaoyi Yin, Xiaohan Shi, Suizhi Gao, Yikai Li, Chuanqi Teng, Shuai Yuan, Xinyu Liu, Zhendong Fu, Xiaochao Kang, Wei Jin, Bin Song, Kailian Zheng, Yijie Zhang, Xiongfei Xu, Shiwei Guo, Gang Jin
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引用次数: 0
Engineered hUCMSC-derived extracellular vesicles deliver circ-0000258 to restore p53-mediated tumor suppression in papillary thyroid carcinoma. 工程hucmsc衍生的细胞外囊泡递送circ-0000258,恢复p53介导的甲状腺乳头状癌肿瘤抑制。
IF 3.4 2区 医学 Q2 ONCOLOGY Pub Date : 2025-12-15 DOI: 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
简介:甲状腺乳头状癌(PTC)是一种重要的内分泌肿瘤,具有多种遗传改变和复杂的分子环境。细胞外囊泡(EVs),特别是来自间充质干细胞(MSCs)的细胞外囊泡(EVs),已成为癌症细胞有前途的靶向药物载体。此外,重编程msc衍生的ev代表了癌症基因治疗的新策略,为临床挑战和新的治疗方向提供了潜在的解决方案。越来越多的证据表明,msc衍生的ev通过传递环状rna (circRNAs)在肿瘤进展中发挥关键作用,环状rna (miRNA)海绵的功能。然而,潜在的分子机制及其临床应用仍有待充分探索和验证。方法与结果:通过高通量生物信息学分析的深入挖掘,我们对PTC组织与正常甲状腺组织进行了全面的差异基因分析,成功鉴定出circ-0000258为关键调控分子。通过PTC细胞系和临床标本的多维度验证,circ-0000258的持续低表达被证实,强烈提示其作为肿瘤抑制因子的潜在潜力。功能机制研究表明,过表达circ-0000258能有效抑制PTC细胞的恶性生物学行为,特别是抑制细胞的增殖和侵袭。更重要的是,circ-0000258作为分子海绵,特异性地隔离miR-146b。这一作用减轻了miR-146b转录后对p53的抑制,从而激活p53介导的凋亡信号级联。通过干预基因调控水平,circ-0000258有效地重编程甲状腺肿瘤细胞的命运。此外,在转化医学研究的背景下,我们创新地构建了基于人脐带间充质干细胞(hucmsc - ev)的细胞外囊泡的工程递送平台。通过外源性负载circ-0000258到这些囊泡中,我们成功地赋予这些天然纳米载体靶向抗癌特性。体外和体内功能实验均表明,负载circ-0000258的工程hucmsc - ev能有效作用于PTC细胞,显著减少异种移植肿瘤的体积,诱导肿瘤细胞凋亡。值得注意的是,当与顺铂联合使用时,这些工程化的细胞外囊泡表现出协同抗癌作用,表明它们有可能克服甲状腺肿瘤的化疗耐药。结论:本研究确立了circ-0000258/miR-146b/p53调控轴是PTC肿瘤抑制的重要机制。它还展示了humcc - ev作为一种安全高效的运载工具的转化潜力。本研究将circ-0000258的功能作用与工程ev的靶向递送优势相结合,不仅为靶向治疗甲状腺癌提供了新的策略,也为新型抗肿瘤生物制剂的开发提供了理论基础和技术范式。它有望将精确肿瘤学领域推进到一个新的水平。
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引用次数: 0
The incidence and risk factors of pulmonary infection complications in lung cancer patients treated with immune checkpoint inhibitors. 免疫检查点抑制剂治疗肺癌患者肺部感染并发症的发生率及危险因素
IF 3.4 2区 医学 Q2 ONCOLOGY Pub Date : 2025-12-15 DOI: 10.1186/s12885-025-15105-9
Haixia Yang, Yaxuan Han, Xiaosha Zhou, Jianying Li, Yanjun Zhao, Shanshan Zhang
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引用次数: 0
Using routine blood tests to predict severe immune-related adverse events during immune checkpoint inhibitor treatment. 使用常规血液检查预测免疫检查点抑制剂治疗期间严重的免疫相关不良事件。
IF 3.4 2区 医学 Q2 ONCOLOGY Pub Date : 2025-12-13 DOI: 10.1186/s12885-025-15460-7
Caner Acar, Fatma Pinar Açar, Gökhan Şahin, Haydar Çağatay Yüksel, Burçak Karaca, Erdem Göker

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}
引用次数: 0
Integrative bulk and single-cell transcriptomic profiling identifies core gene networks and potential therapeutic targets in glioma. 整体和单细胞转录组分析鉴定胶质瘤的核心基因网络和潜在的治疗靶点。
IF 3.4 2区 医学 Q2 ONCOLOGY Pub Date : 2025-12-13 DOI: 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.

背景:神经胶质瘤是最常见的中枢神经系统原发性恶性肿瘤,预后极差。鉴于其高度复杂的分子景观,迫切需要确定新的诊断生物标志物。本研究通过多队列整合和单细胞分析系统地鉴定了胶质瘤核心基因。方法:整合5个GEO转录组数据集(GSE109857、GSE15824、GSE35158、GSE4290和GSE90886,共504个样本),使用ComBat进行批量效应校正。鉴定差异表达基因(deg)并结合加权基因共表达网络分析(WGCNA)获得候选模块。使用CytoHubba、最小绝对收缩和选择算子(LASSO)回归、支持向量机递归特征消除(SVM-RFE)和随机森林(RF)分析等多种方法进一步筛选特征基因。采用外部GEO数据集、受试者工作特征(ROC)分析和基于69个临床样本的实时定量聚合酶链反应(qRT-PCR)进行验证。其他分析包括基因集富集分析(GSEA)、基于cibersort的免疫浸润谱分析、三个单细胞RNA测序(scRNA-seq)数据集(GSE273274、GSE162631和GSE182109)的表达图谱、竞争性内源RNA (ceRNA)和转录因子(TF)网络的构建以及药物富集分析。结果:共鉴定出409个胶质瘤相关候选基因。6个枢纽基因SYP、SYN1、RAB3A、SLC17A7、SYN2和STXBP1在所有算法中一致被鉴定出来。GEO数据集(曲线下面积[AUC]: 0.787-0.802)和临床qRT-PCR验证证实,所有6个基因在胶质瘤中均显著下调。GSEA显示,这些基因的低表达与细胞周期激活、补体和凝血级联以及免疫失调有关。免疫浸润分析显示M1/M2巨噬细胞和活化的NK细胞呈负相关。单细胞分析表明,这些中心基因主要在肿瘤增殖细胞(TPC)样肿瘤细胞中富集,但在胶质瘤核心区域显著减少。竞争的内源性RNA (ceRNA)/TF网络和药物富集分析表明,多层调控机制及其与神经递质相关化合物的关联。结论:6个中心基因在神经胶质瘤中持续下调,具有较强的诊断潜力。它们与免疫微环境和肿瘤细胞谱系的密切联系突出了它们作为生物标志物和潜在治疗靶点的价值。
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引用次数: 0
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BMC Cancer
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