Translational Oncology最新文献_第5页

Diagnostic and prognostic value of EphB2 in nasopharyngeal carcinoma EphB2在鼻咽癌中的诊断及预后价值

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-12-19 DOI: 10.1016/j.tranon.2025.102641

Qiao Huang , Tao Hou , Yi Ren , Wei Xing Liao, Ang Zi Zhu, Ying Liu, Xiao Lin Zhan, Hua Shi Yin

Background

Nasopharyngeal carcinoma (NPC) is a subtype of head and neck carcinoma. This study aimed to investigate the diagnostic and prognostic significance of EphB2 in NPC.

Methods

Serum and nasopharyngeal tissue samples were collected from 159 NPC patients and 159 individuals with chronic nasopharyngeal mucosal inflammation (control group). EphB2 expression in tissue samples was assessed by western blotting (WB) and immunofluorescence (IF); its concentration in serum was measured by enzyme-linked immunosorbent assay (ELISA). Survival rate differences were evaluated using Kaplan–Meier analysis and the log-rank test. Multivariate Cox regression was performed to identify prognosis-related factors. The diagnostic performance of EphB2 was evaluated using receiver operating characteristic (ROC) curves and the area under the curve (AUC).

Results

EphB2 expression was significantly elevated in both serum and tissue samples of NPC patients compared to controls. High EphB2 levels were significantly associated with TNM stage, tumor invasion depth, lymph node metastasis, distant metastases, EBV infection, and recurrence status. Kaplan–Meier survival curves showed that NPC patients with high levels of EphB2 or EBV(+) or recurrence had the poorest disease-free survival. Cox regression identified high EphB2 expression, EBV(+), and recurrence as independent predictors of poor prognosis in NPC. ROC analysis demonstrated that at an optimal cutoff of 7.079 ng/mL, serum EphB2 effectively distinguished NPC patients from controls, with an AUC of 0.904 (95 % CI: 0.866–0.942, P < 0.001), sensitivity of 79.9 %, and specificity of 98.7 %. The AUC for EBV infection alone was 0.767 (95 % CI: 0.714–0.821, P < 0.001), with a sensitivity of 71.1 % and specificity of 82.4 %. Combined detection of EphB2 and EBV infection improved the AUC to 0.922 (95 % CI: 0.891–0.954, P < 0.001), with 78.6 % sensitivity and 97.5 % specificity.

Conclusions

Serum EphB2 represents a promising diagnostic and prognostic biomarker for NPC. The combination of EBV seropositivity and high EphB2 expression may be valuable for early NPC screening.

鼻咽癌（NPC）是头颈癌的一个亚型。本研究旨在探讨EphB2在鼻咽癌中的诊断及预后意义。方法采集159例鼻咽癌患者和159例慢性鼻咽黏膜炎症患者（对照组）的血清和鼻咽组织标本。采用western blotting （WB）和免疫荧光（IF）检测组织样品中EphB2的表达；采用酶联免疫吸附试验（ELISA）测定其血清浓度。生存率差异采用Kaplan-Meier分析和log-rank检验。采用多因素Cox回归分析确定预后相关因素。采用受试者工作特征曲线（ROC）和曲线下面积（AUC）评价EphB2的诊断效能。结果鼻咽癌患者血清和组织标本中tsephb2的表达均明显高于对照组。高水平EphB2与TNM分期、肿瘤侵袭深度、淋巴结转移、远处转移、EBV感染和复发情况显著相关。Kaplan-Meier生存曲线显示，高水平EphB2或EBV（+）或复发的鼻咽癌患者无病生存期最差。Cox回归发现EphB2高表达、EBV（+）和复发是鼻咽癌预后不良的独立预测因素。ROC分析显示，在最佳截断值为7.079 ng/mL时，血清EphB2可有效区分鼻咽癌患者和对照组，AUC为0.904 (95% CI: 0.866-0.942, P < 0.001)，敏感性为79.9%，特异性为98.7%。单独EBV感染的AUC为0.767 (95% CI: 0.714-0.821, P < 0.001)，敏感性为71.1%，特异性为82.4%。联合检测EphB2和EBV感染使AUC提高到0.922 (95% CI: 0.891 ~ 0.954, P < 0.001)，敏感性78.6%，特异性97.5%。结论血清EphB2是鼻咽癌诊断和预后的良好生物标志物。EBV血清阳性和EphB2高表达的结合可能对鼻咽癌早期筛查有价值。

{"title":"Diagnostic and prognostic value of EphB2 in nasopharyngeal carcinoma","authors":"Qiao Huang , Tao Hou , Yi Ren , Wei Xing Liao, Ang Zi Zhu, Ying Liu, Xiao Lin Zhan, Hua Shi Yin","doi":"10.1016/j.tranon.2025.102641","DOIUrl":"10.1016/j.tranon.2025.102641","url":null,"abstract":"<div><h3>Background</h3><div>Nasopharyngeal carcinoma (NPC) is a subtype of head and neck carcinoma. This study aimed to investigate the diagnostic and prognostic significance of EphB2 in NPC.</div></div><div><h3>Methods</h3><div>Serum and nasopharyngeal tissue samples were collected from 159 NPC patients and 159 individuals with chronic nasopharyngeal mucosal inflammation (control group). EphB2 expression in tissue samples was assessed by western blotting (WB) and immunofluorescence (IF); its concentration in serum was measured by enzyme-linked immunosorbent assay (ELISA). Survival rate differences were evaluated using Kaplan–Meier analysis and the log-rank test. Multivariate Cox regression was performed to identify prognosis-related factors. The diagnostic performance of EphB2 was evaluated using receiver operating characteristic (ROC) curves and the area under the curve (AUC).</div></div><div><h3>Results</h3><div>EphB2 expression was significantly elevated in both serum and tissue samples of NPC patients compared to controls. High EphB2 levels were significantly associated with TNM stage, tumor invasion depth, lymph node metastasis, distant metastases, EBV infection, and recurrence status. Kaplan–Meier survival curves showed that NPC patients with high levels of EphB2 or EBV(+) or recurrence had the poorest disease-free survival. Cox regression identified high EphB2 expression, EBV(+), and recurrence as independent predictors of poor prognosis in NPC. ROC analysis demonstrated that at an optimal cutoff of 7.079 ng/mL, serum EphB2 effectively distinguished NPC patients from controls, with an AUC of 0.904 (95 % CI: 0.866–0.942, <em>P</em> < 0.001), sensitivity of 79.9 %, and specificity of 98.7 %. The AUC for EBV infection alone was 0.767 (95 % CI: 0.714–0.821, <em>P</em> < 0.001), with a sensitivity of 71.1 % and specificity of 82.4 %. Combined detection of EphB2 and EBV infection improved the AUC to 0.922 (95 % CI: 0.891–0.954, <em>P</em> < 0.001), with 78.6 % sensitivity and 97.5 % specificity.</div></div><div><h3>Conclusions</h3><div>Serum EphB2 represents a promising diagnostic and prognostic biomarker for NPC. The combination of EBV seropositivity and high EphB2 expression may be valuable for early NPC screening.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102641"},"PeriodicalIF":5.0,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798220","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

Evaluation of the anti-tumor efficacy of prodigiosin in papillary thyroid cancer cell and animal models 神子红素对甲状腺乳头状癌细胞及动物模型的抗肿瘤作用评价。

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-12-18 DOI: 10.1016/j.tranon.2025.102648

Meiyu Liu , Junwei Huang , Mengqiao Dai , Xiaoni Gao , Zihang Ai , Wei Hu , Zanbing Li , feijie wang , Junjie Yang , Haidong Liao , Yang Xie , Yong Ying , Xiangtai Zeng

Objective

: To investigate the anti-tumor efficacy and underlying molecular mechanisms of prodigiosin (PG) in papillary thyroid cancer (PTC).

Methods

: The anti-cancer effects of PG were systematically evaluated in vitro using PTC cell lines and in vivo via xenograft mouse models. Cell viability and dose-response relationships were determined by CCK-8 assays. Anti-proliferative activity was assessed through colony formation and EdU incorporation assays. The impact on metastatic potential was examined by scratch wound healing and Matrigel-based transwell migration and invasion assays. Cell cycle distribution was analyzed using flow cytometry.

Results

: In vitro, PG at 500 nM inhibited the growth of BCPAP and TPC-1 cells by 93.5 % and 89.2 %, respectively, as determined by colony formation assays. Migration and invasion of BCPAP cells were reduced by 90.7 % and 93.4 %, measured via scratch wound healing and transwell assays. PG treatment modulated epithelial-mesenchymal transition (EMT) markers both in vitro and in vivo, characterized by downregulating mesenchymal proteins and upregulating epithelial proteins, accompanied by changes in Wnt/β-catenin pathway-related proteins, indicating suppression of EMT. Flow cytometry revealed that PG induced G0/G1 cell cycle arrest in both BCPAP and TPC-1 cells. Furthermore, PG upregulated the sodium-iodide symporter (NIS), enhancing radioiodine uptake. Moreover, the treatment of PG significantly inhibited tumor growth without notable toxicity in vivo.

Conclusion

: PG exerts potent anti-tumor activity against PTC by simultaneously inhibiting proliferation, migration, and invasion, inducing cell cycle arrest, and enhancing radioiodine uptake, potentially through modulation of the Wnt/β-catenin signaling pathway. Our findings position PG as a highly promising, potentially transformative therapeutic candidate for PTC, offering a strategic approach to overcome conventional therapy resistance and improve clinical outcomes.

目的：探讨芥子红素（PG）对甲状腺乳头状癌（PTC）的抗肿瘤作用及其分子机制。方法：采用PTC细胞系和小鼠异种移植模型，系统评价PG的体外抗癌作用。通过CCK-8测定细胞活力和剂量-反应关系。通过菌落形成和EdU掺入试验评估抗增殖活性。通过划伤愈合和基于matrigel的跨井迁移和侵袭试验来检查对转移潜力的影响。流式细胞术分析细胞周期分布。结果：体外集落形成实验表明，PG在500 nM下对BCPAP和TPC-1细胞的生长抑制作用分别为93.5%和89.2%。通过划痕伤口愈合和transwell实验测量，BCPAP细胞的迁移和侵袭分别减少了90.7%和93.4%。PG处理在体外和体内均可调节上皮-间充质转化（EMT）标志物，表现为下调间充质蛋白和上调上皮蛋白，同时伴有Wnt/β-catenin通路相关蛋白的变化，表明EMT受到抑制。流式细胞术显示PG诱导BCPAP和TPC-1细胞的G0/G1细胞周期阻滞。此外，PG上调了碘化钠同调体（NIS），增强了放射性碘的摄取。此外，PG治疗可显著抑制肿瘤生长，体内无明显毒性。结论：PG可能通过调控Wnt/β-catenin信号通路，同时抑制PTC的增殖、迁移和侵袭，诱导细胞周期阻滞，增强放射性碘摄取，对PTC具有较强的抗肿瘤活性。我们的研究结果表明，PG是一种非常有前途的、具有潜在变革性的PTC治疗候选药物，为克服常规治疗耐药性和改善临床结果提供了战略途径。

{"title":"Evaluation of the anti-tumor efficacy of prodigiosin in papillary thyroid cancer cell and animal models","authors":"Meiyu Liu , Junwei Huang , Mengqiao Dai , Xiaoni Gao , Zihang Ai , Wei Hu , Zanbing Li , feijie wang , Junjie Yang , Haidong Liao , Yang Xie , Yong Ying , Xiangtai Zeng","doi":"10.1016/j.tranon.2025.102648","DOIUrl":"10.1016/j.tranon.2025.102648","url":null,"abstract":"<div><h3>Objective</h3><div><strong>:</strong> To investigate the anti-tumor efficacy and underlying molecular mechanisms of prodigiosin (PG) in papillary thyroid cancer (PTC).</div></div><div><h3>Methods</h3><div><strong>:</strong> The anti-cancer effects of PG were systematically evaluated <em>in vitro</em> using PTC cell lines and <em>in vivo</em> via xenograft mouse models. Cell viability and dose-response relationships were determined by CCK-8 assays. Anti-proliferative activity was assessed through colony formation and EdU incorporation assays. The impact on metastatic potential was examined by scratch wound healing and Matrigel-based transwell migration and invasion assays. Cell cycle distribution was analyzed using flow cytometry.</div></div><div><h3>Results</h3><div><strong>:</strong> In vitro, PG at 500 nM inhibited the growth of BCPAP and TPC-1 cells by 93.5 % and 89.2 %, respectively, as determined by colony formation assays. Migration and invasion of BCPAP cells were reduced by 90.7 % and 93.4 %, measured via scratch wound healing and transwell assays. PG treatment modulated epithelial-mesenchymal transition (EMT) markers both <em>in vitro</em> and <em>in vivo</em>, characterized by downregulating mesenchymal proteins and upregulating epithelial proteins, accompanied by changes in Wnt/β-catenin pathway-related proteins, indicating suppression of EMT. Flow cytometry revealed that PG induced G0/G1 cell cycle arrest in both BCPAP and TPC-1 cells. Furthermore, PG upregulated the sodium-iodide symporter (NIS), enhancing radioiodine uptake. Moreover, the treatment of PG significantly inhibited tumor growth without notable toxicity <em>in vivo</em>.</div></div><div><h3>Conclusion</h3><div><strong>:</strong> PG exerts potent anti-tumor activity against PTC by simultaneously inhibiting proliferation, migration, and invasion, inducing cell cycle arrest, and enhancing radioiodine uptake, potentially through modulation of the Wnt/β-catenin signaling pathway. Our findings position PG as a highly promising, potentially transformative therapeutic candidate for PTC, offering a strategic approach to overcome conventional therapy resistance and improve clinical outcomes.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102648"},"PeriodicalIF":5.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145795007","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

The stem cell atlas of lung adenocarcinoma: A stemness blueprint for prognosis and immunotherapy success 肺腺癌的干细胞图谱：预测预后和免疫治疗成功的干细胞蓝图。

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-12-17 DOI: 10.1016/j.tranon.2025.102639

Jiacheng Yin , Xing Jin , Zhengyang Hu , Huiqiang Yang , Shuhua Huo , Fenghao Sun , Wei Jiang , Qun Wang , Qihai Sui , Yu Shi , Zhencong Chen

Cancer stem cells (CSCs) are involved in tumor initiation, metastasis, therapeutic resistance, and heterogeneity of aggressive lung adenocarcinomas (LUADs). Although identification of CSCs through cell surface markers expression defines the CSC compartment, it provides little information on molecular mechanisms underlying the biological behaviors of CSCs. The CSC-driving tumor evolution path is also largely unknown due to technical difficulties. This study aimed to comprehensively depict the landscape of LUAD CSCs at the single-cell and molecular levels.

Through flow cytometry and lineage tracing, we reconstructed LUAD CSCs trajectories with patient-derived samples and identified a persistent stem-like population with distinct molecular signatures through all tumor stages. CSC-related pathways, transcription factors (TFs) and metabolic characteristics were differentially expressed along LUAD progression, which revealed that developmental trajectory and tumor heterogeneity were driven by multistep transcriptional reprogramming of CSCs. Moreover, CSCs might promote LUAD progression through the S100A9-pNF-κB axis. We discovered a specific stemness signature with genetic profiles along the tumor progression and significantly correlated with clinical outcomes. Notably, by integrating bulk tumor data from TCGA, molecular clustering based on the CSC stemness signature well-distinguished clinical features and genomic or immune alterations, with the high stemness index group exhibiting reduced immune activity and a tendency towards cold tumors.

Overall, our results provided unique perspectives into previously unappreciated molecular dynamics of CSC subpopulations driving LUAD evolution. The stemness signature tailored personalized risk assessment and immunotherapy strategies for individual LUAD patients.

肿瘤干细胞（CSCs）参与侵袭性肺腺癌（LUADs）的肿瘤起始、转移、治疗抵抗和异质性。虽然通过细胞表面标记物表达对CSC进行鉴定定义了CSC区室，但它对CSC生物学行为背后的分子机制提供的信息很少。由于技术上的困难，csc驱动的肿瘤进化路径在很大程度上也是未知的。本研究旨在从单细胞和分子水平全面描绘LUAD CSCs的景观。通过流式细胞术和谱系追踪，我们用患者来源的样本重建了LUAD CSCs的轨迹，并确定了在所有肿瘤阶段具有不同分子特征的持续的茎样群体。随着LUAD的进展，csc相关通路、转录因子（tf）和代谢特征的表达存在差异，这表明csc的发育轨迹和肿瘤异质性是由多步转录重编程驱动的。此外，CSCs可能通过S100A9-pNF-κB轴促进LUAD进展。我们发现了一种特定的干性特征，它与肿瘤进展的遗传谱有关，并与临床结果显著相关。值得注意的是，通过整合来自TCGA的大量肿瘤数据，基于CSC干性特征的分子聚类很好地区分了临床特征和基因组或免疫改变，高干性指数组表现出免疫活性降低和冷肿瘤倾向。总的来说，我们的研究结果为以前未被重视的CSC亚群驱动LUAD进化的分子动力学提供了独特的视角。stemness签名为个体LUAD患者量身定制个性化风险评估和免疫治疗策略。

{"title":"The stem cell atlas of lung adenocarcinoma: A stemness blueprint for prognosis and immunotherapy success","authors":"Jiacheng Yin , Xing Jin , Zhengyang Hu , Huiqiang Yang , Shuhua Huo , Fenghao Sun , Wei Jiang , Qun Wang , Qihai Sui , Yu Shi , Zhencong Chen","doi":"10.1016/j.tranon.2025.102639","DOIUrl":"10.1016/j.tranon.2025.102639","url":null,"abstract":"<div><div>Cancer stem cells (CSCs) are involved in tumor initiation, metastasis, therapeutic resistance, and heterogeneity of aggressive lung adenocarcinomas (LUADs). Although identification of CSCs through cell surface markers expression defines the CSC compartment, it provides little information on molecular mechanisms underlying the biological behaviors of CSCs. The CSC-driving tumor evolution path is also largely unknown due to technical difficulties. This study aimed to comprehensively depict the landscape of LUAD CSCs at the single-cell and molecular levels.</div><div>Through flow cytometry and lineage tracing, we reconstructed LUAD CSCs trajectories with patient-derived samples and identified a persistent stem-like population with distinct molecular signatures through all tumor stages. CSC-related pathways, transcription factors (TFs) and metabolic characteristics were differentially expressed along LUAD progression, which revealed that developmental trajectory and tumor heterogeneity were driven by multistep transcriptional reprogramming of CSCs. Moreover, CSCs might promote LUAD progression through the S100A9-pNF-κB axis. We discovered a specific stemness signature with genetic profiles along the tumor progression and significantly correlated with clinical outcomes. Notably, by integrating bulk tumor data from TCGA, molecular clustering based on the CSC stemness signature well-distinguished clinical features and genomic or immune alterations, with the high stemness index group exhibiting reduced immune activity and a tendency towards cold tumors.</div><div>Overall, our results provided unique perspectives into previously unappreciated molecular dynamics of CSC subpopulations driving LUAD evolution. The stemness signature tailored personalized risk assessment and immunotherapy strategies for individual LUAD patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102639"},"PeriodicalIF":5.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145782998","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

Multi-omics characterization identifies AHCY as a prognostic biomarker driving immunometabolic reprogramming in bladder cancer 多组学鉴定鉴定AHCY是膀胱癌中驱动免疫代谢重编程的预后生物标志物。

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-12-17 DOI: 10.1016/j.tranon.2025.102652

Qiao Peng , Mengmei Zhang , Shuyu Zhao , Yadong Guo , Minjue Shan , Baimei Su , Shiyu Mao , Donghui Shi , Ziyou Lin

Introduction

Bladder cancer (BLCA) is a heterogeneous malignancy with poor prognosis and limited biomarkers for risk stratification and therapy guidance. Adenosylhomocysteinase (AHCY), a key enzyme in the methionine cycle, has been implicated in tumor progression and epigenetic regulation, but its clinical and biological significance in BLCA remains unclear.

Methods

We performed an integrative pan-cancer and BLCA-focused analysis using TCGA, GTEx, and multiple independent datasets. Multi-omics data, including transcriptomic, genomic, epigenetic, immune, and drug sensitivity profiles, were systematically analyzed. Prognostic associations were evaluated by Cox and Kaplan–Meier analyses, and in vitro knockdown assays were conducted to assess AHCY function in BLCA cells.

Results

AHCY was significantly upregulated across diverse cancers and correlated with poor overall, disease-specific, and progression-free survival. In BLCA, AHCY overexpression was driven by copy number amplification and promoter hypomethylation, and was associated with enhanced cell cycle progression, DNA replication, and pyrimidine metabolism, while negatively linked to apoptosis and immune activation. High AHCY expression correlated with immune infiltration but impaired effector responses, predicted poor immunotherapy outcomes, and conferred resistance to chemotherapeutics and targeted agents across PRISM, CTRP, and GDSC datasets. Functional assays confirmed that AHCY depletion suppressed proliferation, induced apoptosis, and promoted ferroptosis by downregulating SLC7A11 and upregulating ACSL4 and 4-HNE.

Conclusions

Our findings identify AHCY as a prognostic biomarker and immunometabolic regulator in BLCA, linking methionine metabolism to tumor progression, immune suppression, and drug resistance. AHCY holds promise as a therapeutic target and companion biomarker for precision oncology.

膀胱癌（BLCA）是一种预后较差的异质性恶性肿瘤，其风险分层和治疗指导的生物标志物有限。腺苷高半胱氨酸酶（AHCY）是蛋氨酸循环中的关键酶，与肿瘤进展和表观遗传调控有关，但其在BLCA中的临床和生物学意义尚不清楚。方法：我们使用TCGA、GTEx和多个独立数据集进行了以泛癌症和blca为重点的综合分析。系统分析多组学数据，包括转录组学、基因组学、表观遗传学、免疫和药物敏感性谱。通过Cox和Kaplan-Meier分析评估预后相关性，并进行体外敲低试验以评估AHCY在BLCA细胞中的功能。结果：AHCY在多种癌症中显著上调，并与较差的总体、疾病特异性和无进展生存期相关。在BLCA中，AHCY过表达是由拷贝数扩增和启动子低甲基化驱动的，与细胞周期进程、DNA复制和嘧啶代谢的增强有关，而与细胞凋亡和免疫激活呈负相关。在PRISM、CTRP和GDSC数据集中，高AHCY表达与免疫浸润相关，但效应反应受损，预测免疫治疗结果较差，并赋予化疗药物和靶向药物耐药。功能实验证实AHCY缺失通过下调SLC7A11、上调ACSL4和4-HNE抑制细胞增殖、诱导细胞凋亡、促进铁下垂。结论：我们的研究结果确定AHCY是BLCA的预后生物标志物和免疫代谢调节剂，将蛋氨酸代谢与肿瘤进展、免疫抑制和耐药性联系起来。AHCY有望成为精准肿瘤学的治疗靶点和伴生生物标志物。

{"title":"Multi-omics characterization identifies AHCY as a prognostic biomarker driving immunometabolic reprogramming in bladder cancer","authors":"Qiao Peng , Mengmei Zhang , Shuyu Zhao , Yadong Guo , Minjue Shan , Baimei Su , Shiyu Mao , Donghui Shi , Ziyou Lin","doi":"10.1016/j.tranon.2025.102652","DOIUrl":"10.1016/j.tranon.2025.102652","url":null,"abstract":"<div><h3>Introduction</h3><div>Bladder cancer (BLCA) is a heterogeneous malignancy with poor prognosis and limited biomarkers for risk stratification and therapy guidance. Adenosylhomocysteinase (AHCY), a key enzyme in the methionine cycle, has been implicated in tumor progression and epigenetic regulation, but its clinical and biological significance in BLCA remains unclear.</div></div><div><h3>Methods</h3><div>We performed an integrative pan-cancer and BLCA-focused analysis using TCGA, GTEx, and multiple independent datasets. Multi-omics data, including transcriptomic, genomic, epigenetic, immune, and drug sensitivity profiles, were systematically analyzed. Prognostic associations were evaluated by Cox and Kaplan–Meier analyses, and in vitro knockdown assays were conducted to assess AHCY function in BLCA cells.</div></div><div><h3>Results</h3><div>AHCY was significantly upregulated across diverse cancers and correlated with poor overall, disease-specific, and progression-free survival. In BLCA, AHCY overexpression was driven by copy number amplification and promoter hypomethylation, and was associated with enhanced cell cycle progression, DNA replication, and pyrimidine metabolism, while negatively linked to apoptosis and immune activation. High AHCY expression correlated with immune infiltration but impaired effector responses, predicted poor immunotherapy outcomes, and conferred resistance to chemotherapeutics and targeted agents across PRISM, CTRP, and GDSC datasets. Functional assays confirmed that AHCY depletion suppressed proliferation, induced apoptosis, and promoted ferroptosis by downregulating SLC7A11 and upregulating ACSL4 and 4-HNE.</div></div><div><h3>Conclusions</h3><div>Our findings identify AHCY as a prognostic biomarker and immunometabolic regulator in BLCA, linking methionine metabolism to tumor progression, immune suppression, and drug resistance. AHCY holds promise as a therapeutic target and companion biomarker for precision oncology.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102652"},"PeriodicalIF":5.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145782969","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

Corrigendum to “Clinical significance and molecular mechanism of CDX2-CBX3 regulatory axis in lung adenocarcinoma progression” [Transl Oncol. 2025 Nov 10:63:102590] “CDX2-CBX3调节轴在肺腺癌进展中的临床意义和分子机制”的勘误表[trans - oncology . 2025 Nov 10:63:102590]

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-12-17 DOI: 10.1016/j.tranon.2025.102637

Shicheng Liu , Qingtao Zhao , Dahu Ren , Lingxin Kong , Hongzhen Zhao , Guochen Duan

引用次数: 0

Single-cell profiling of bone metastasis ecosystems reveals pivotal role of INSR+AEC in clear cell renal cell carcinoma 骨转移生态系统的单细胞谱揭示了INSR+AEC在透明细胞肾细胞癌中的关键作用。

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-12-16 DOI: 10.1016/j.tranon.2025.102650

Haixiang Zhang , Jiafeng Hou , Long Zhang , Peng Luo , Hanzhong Zhang , Aiming Jiang , Xuebing Ren , Chunbiao Wu

Background

Bone metastasis is a common and lethal complication of advanced clear cell renal cell carcinoma (ccRCC), yet the cellular and spatial architecture of the human bone metastatic niche remains incompletely defined, limiting identification of actionable targets.

Methods

We integrated matched single cell RNA sequencing with spatial transcriptomics and large scale bulk cohorts. Integrating multi computational pipelines to derive and validate an INSR⁺ artery endothelial relevant prognostic signature (IAERS). Functional consequences of COL4A1 were assessed with in vitro experiments.

Results

Single cell and spatial analyses uncovered pronounced malignant cell heterogeneity and a metastatic malignant programme enriched for extracellular matrix and adhesion pathways. Endothelial cells displayed the strongest inferred crosstalk with metastatic tumour cells; an INSR⁺ AEC subset was selectively enriched in bone metastases and spatially colocalized with metastatic foci. Ligand-receptor modelling identified a dominant COL4A1-SDC4 signalling axis linking INSR⁺ AEC to metastatic tumo ur cells, and GeneSwitches nominated TCF4 as a transcriptional switch sustaining the INSR⁺ AEC programme. COL4A1 knockdown impaired ccRCC proliferation, migration and invasion in vitro. A novel IAERS signature derived from INSR⁺ AEC programmes robustly stratified patient survival and metastatic status across independent cohorts.

Conclusions

These multi‑modal data define a prometastatic vascular niche in ccRCC centred on TCF4 associated INSR⁺ AEC and a COL4A1-SDC4 axis, providing candidate biomarkers and therapeutic avenues that target endothelial matrix interactions in bone metastatic disease.

背景：骨转移是晚期透明细胞肾细胞癌（ccRCC）常见且致命的并发症，然而人类骨转移生态位的细胞和空间结构仍然不完全确定，限制了可操作靶点的识别。方法：我们将匹配的单细胞RNA测序与空间转录组学和大规模批量队列相结合。整合多个计算管道来推导和验证INSR+动脉内皮相关预后特征（IAERS）。通过体外实验评估COL4A1的功能影响。结果：单细胞和空间分析揭示了明显的恶性细胞异质性和转移性恶性程序丰富的细胞外基质和粘附途径。内皮细胞与转移性肿瘤细胞表现出最强的推断串扰；INSR+ AEC亚群在骨转移中选择性富集，并在空间上与转移灶共定位。配体-受体模型鉴定了连接INSR+ AEC与转移性肿瘤细胞的显性COL4A1-SDC4信号轴，geneswitch提名TCF4作为维持INSR+ AEC程序的转录开关。COL4A1敲低可抑制ccRCC体外增殖、迁移和侵袭。来自INSR+ AEC项目的一种新的IAERS特征在独立队列中对患者生存和转移状态进行了强有力的分层。结论：这些多模式数据定义了以TCF4相关的INSR+ AEC和COL4A1-SDC4轴为中心的ccRCC的原转移性血管生态位，提供了靶向骨转移疾病中内皮基质相互作用的候选生物标志物和治疗途径。

{"title":"Single-cell profiling of bone metastasis ecosystems reveals pivotal role of INSR+AEC in clear cell renal cell carcinoma","authors":"Haixiang Zhang , Jiafeng Hou , Long Zhang , Peng Luo , Hanzhong Zhang , Aiming Jiang , Xuebing Ren , Chunbiao Wu","doi":"10.1016/j.tranon.2025.102650","DOIUrl":"10.1016/j.tranon.2025.102650","url":null,"abstract":"<div><h3>Background</h3><div>Bone metastasis is a common and lethal complication of advanced clear cell renal cell carcinoma (ccRCC), yet the cellular and spatial architecture of the human bone metastatic niche remains incompletely defined, limiting identification of actionable targets.</div></div><div><h3>Methods</h3><div>We integrated matched single cell RNA sequencing with spatial transcriptomics and large scale bulk cohorts. Integrating multi computational pipelines to derive and validate an INSR<sup>+</sup> artery endothelial relevant prognostic signature (IAERS). Functional consequences of <em>COL4A1</em> were assessed with in vitro experiments.</div></div><div><h3>Results</h3><div>Single cell and spatial analyses uncovered pronounced malignant cell heterogeneity and a metastatic malignant programme enriched for extracellular matrix and adhesion pathways. Endothelial cells displayed the strongest inferred crosstalk with metastatic tumour cells; an INSR<sup>+</sup> AEC subset was selectively enriched in bone metastases and spatially colocalized with metastatic foci. Ligand-receptor modelling identified a dominant <em>COL4A1</em>-<em>SDC4</em> signalling axis linking INSR<sup>+</sup> AEC to metastatic tumo ur cells, and GeneSwitches nominated <em>TCF4</em> as a transcriptional switch sustaining the INSR<sup>+</sup> AEC programme. <em>COL4A1</em> knockdown impaired ccRCC proliferation, migration and invasion in vitro. A novel IAERS signature derived from INSR<sup>+</sup> AEC programmes robustly stratified patient survival and metastatic status across independent cohorts.</div></div><div><h3>Conclusions</h3><div>These multi‑modal data define a prometastatic vascular niche in ccRCC centred on <em>TCF4</em> associated INSR<sup>+</sup> AEC and a <em>COL4A1</em>-<em>SDC4</em> axis, providing candidate biomarkers and therapeutic avenues that target endothelial matrix interactions in bone metastatic disease.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102650"},"PeriodicalIF":5.0,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774486","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

Exploration of precise classification and therapeutic targets of breast cancer based on genes related to neuro-cancer crosstalk 基于神经肿瘤串扰相关基因的乳腺癌精确分类和治疗靶点探索。

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-12-16 DOI: 10.1016/j.tranon.2025.102647

Zhi Li , Chang Sun , Yangyang Cui , Yue Huang , Mingduo Liu , Hui Xie , Shui Wang

This investigation examines neural-cancer crosstalk in breast cancer, utilizing TCGA/GEO transcriptomic and single-cell data to develop a neural-cancer crosstalk prognostic signature and evaluate its clinical relevance. We identified four core genes—L1CAM, TACR1, GFRA1, and NTRK3—using univariate Cox regression and LASSO-Cox regression to develop a risk scoring model. The prognostic signature showed consistent predictive accuracy across validation cohorts, with high-risk patients demonstrating markedly reduced survival. Multivariate analysis established the risk score as an independent prognostic indicator. Immune profiling identified an immunosuppressive phenotype in high-risk cases, featuring elevated Treg infiltration and impaired antigen presentation. Genomic analysis revealed significantly higher TP53 mutation frequency in high-risk versus low-risk patients. Drug sensitivity predictions indicated that the high-risk group exhibited increased sensitivity to targeted therapies such as Lapatinib, but enhanced resistance to conventional chemotherapy. Single-cell sequencing revealed the heterogeneity of breast cancer cells and elucidated a neuro-immune-tumor interaction network dominated by MIF and MDK signaling pathways. Functional validation studies demonstrated that L1CAM knockdown effectively suppressed malignant phenotypes in breast cancer cells, including proliferation, migration, and invasive capacity in vitro. This study provides new insights into the regulatory mechanisms of the neural microenvironment in breast cancer, and the established prognostic model and identified potential therapeutic targets hold significant clinical implications for personalized treatment.

本研究利用TCGA/GEO转录组学和单细胞数据，研究了乳腺癌中的神经肿瘤串扰，以建立神经肿瘤串扰预后特征并评估其临床相关性。通过单变量Cox回归和LASSO-Cox回归，我们确定了四个核心基因——l1cam、TACR1、GFRA1和ntrk3，并建立了风险评分模型。预后特征在验证队列中显示一致的预测准确性，高风险患者的生存率明显降低。多变量分析将风险评分作为独立的预后指标。免疫谱分析在高危病例中发现了免疫抑制表型，其特征是Treg浸润升高和抗原呈递受损。基因组分析显示，高危患者的TP53突变频率明显高于低危患者。药物敏感性预测表明，高危组对拉帕替尼等靶向治疗的敏感性增加，但对常规化疗的耐药性增强。单细胞测序揭示了乳腺癌细胞的异质性，并阐明了由MIF和MDK信号通路主导的神经-免疫-肿瘤相互作用网络。功能验证研究表明，L1CAM敲低可有效抑制乳腺癌细胞的恶性表型，包括体外增殖、迁移和侵袭能力。本研究为乳腺癌神经微环境的调控机制提供了新的认识，建立的预后模型和确定的潜在治疗靶点对个性化治疗具有重要的临床意义。

{"title":"Exploration of precise classification and therapeutic targets of breast cancer based on genes related to neuro-cancer crosstalk","authors":"Zhi Li , Chang Sun , Yangyang Cui , Yue Huang , Mingduo Liu , Hui Xie , Shui Wang","doi":"10.1016/j.tranon.2025.102647","DOIUrl":"10.1016/j.tranon.2025.102647","url":null,"abstract":"<div><div>This investigation examines neural-cancer crosstalk in breast cancer, utilizing TCGA/GEO transcriptomic and single-cell data to develop a neural-cancer crosstalk prognostic signature and evaluate its clinical relevance. We identified four core genes—L1CAM, TACR1, GFRA1, and NTRK3—using univariate Cox regression and LASSO-Cox regression to develop a risk scoring model. The prognostic signature showed consistent predictive accuracy across validation cohorts, with high-risk patients demonstrating markedly reduced survival. Multivariate analysis established the risk score as an independent prognostic indicator. Immune profiling identified an immunosuppressive phenotype in high-risk cases, featuring elevated Treg infiltration and impaired antigen presentation. Genomic analysis revealed significantly higher TP53 mutation frequency in high-risk versus low-risk patients. Drug sensitivity predictions indicated that the high-risk group exhibited increased sensitivity to targeted therapies such as Lapatinib, but enhanced resistance to conventional chemotherapy. Single-cell sequencing revealed the heterogeneity of breast cancer cells and elucidated a neuro-immune-tumor interaction network dominated by MIF and MDK signaling pathways. Functional validation studies demonstrated that L1CAM knockdown effectively suppressed malignant phenotypes in breast cancer cells, including proliferation, migration, and invasive capacity in vitro. This study provides new insights into the regulatory mechanisms of the neural microenvironment in breast cancer, and the established prognostic model and identified potential therapeutic targets hold significant clinical implications for personalized treatment.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102647"},"PeriodicalIF":5.0,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774195","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

Radiomics as a visual tool with potential clinical implications: A comment on the implementation of habitat radiomics in a liver cancer series 放射组学作为一种具有潜在临床意义的视觉工具：对生境放射组学在肝癌系列中的实施的评论。

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-12-15 DOI: 10.1016/j.tranon.2025.102640

Francesco Fiz , Angela Ammirabile , Luca Viganò

引用次数: 0

Unraveling the anti-cancer potential of procyanidin B2 from grape seeds in gastric cancer through a multi-omics approach with emphasis on ROS and ferroptosis 通过多组学方法揭示葡萄籽原花青素B2在胃癌中的抗癌潜力，重点是ROS和铁下垂。

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-12-15 DOI: 10.1016/j.tranon.2025.102642

Zhejin Li , Nannan Song , Yawen Deng , Qingqing Zhang , Fanglong Hu , Yanfang Lu , Jinting Chen , Pengfei Xiao , Ao Yan , Jianheng Li , Zongjin Guo , Chengyan Zhou

Some flavonoids have been reported to enhance metal-catalyzed Fenton reactions, leading to excessive reactive oxygen species (ROS) and oxidative stress. Procyanidin B2 (PB2) is a plant-derived flavonoid whose anticancer activity has been attributed to inhibition of tumorigenesis-related signaling pathways in previous studies. However, the role of oxidative stress in the therapeutic activity of PB2 against gastric cancer remains unexplored. Beyond evaluating the anticancer potential of PB2 in proliferation, migration, cell death, and immune cell recruitment, we concentrated on alterations in intracellular redox state following PB2 treatment in gastric cancer cells. Through metabolomic and transcriptomic screening, we identified pathways altered by PB2 in gastric cancer cells, focusing on oxidative stress related biological functions, which were further confirmed through in vitro and in vivo validation. The heightened oxidative levels resulting from PB2 treatment induce endoplasmic reticulum stress and promote apoptosis. Furthermore, PB2 enhances autophagic flux to increase cellular free iron and promote ferroptosis. All in all, our research provides a comprehensive perspective on the therapeutic potential of PB2 in treating gastric cancer, demonstrating its capacity to inhibit growth signals and induce oxidative stress-related cell death.

据报道，一些类黄酮可以增强金属催化的Fenton反应，导致活性氧（ROS）过多和氧化应激。原花青素B2 （Procyanidin B2, PB2）是一种植物来源的类黄酮，其抗癌活性在先前的研究中被认为是抑制肿瘤发生相关的信号通路。然而，氧化应激在PB2抗胃癌治疗活性中的作用仍未被探索。除了评估PB2在增殖、迁移、细胞死亡和免疫细胞募集方面的抗癌潜力外，我们还关注了PB2治疗胃癌细胞后细胞内氧化还原状态的改变。通过代谢组学和转录组学筛选，我们在胃癌细胞中发现了PB2改变的通路，重点关注氧化应激相关的生物学功能，并通过体外和体内验证进一步证实。PB2处理引起的氧化水平升高诱导内质网应激并促进细胞凋亡。此外，PB2增强自噬通量，增加细胞游离铁，促进铁凋亡。总之，我们的研究为PB2治疗胃癌的治疗潜力提供了一个全面的视角，证明了其抑制生长信号和诱导氧化应激相关细胞死亡的能力。

{"title":"Unraveling the anti-cancer potential of procyanidin B2 from grape seeds in gastric cancer through a multi-omics approach with emphasis on ROS and ferroptosis","authors":"Zhejin Li , Nannan Song , Yawen Deng , Qingqing Zhang , Fanglong Hu , Yanfang Lu , Jinting Chen , Pengfei Xiao , Ao Yan , Jianheng Li , Zongjin Guo , Chengyan Zhou","doi":"10.1016/j.tranon.2025.102642","DOIUrl":"10.1016/j.tranon.2025.102642","url":null,"abstract":"<div><div>Some flavonoids have been reported to enhance metal-catalyzed Fenton reactions, leading to excessive reactive oxygen species (ROS) and oxidative stress. Procyanidin B2 (PB2) is a plant-derived flavonoid whose anticancer activity has been attributed to inhibition of tumorigenesis-related signaling pathways in previous studies. However, the role of oxidative stress in the therapeutic activity of PB2 against gastric cancer remains unexplored. Beyond evaluating the anticancer potential of PB2 in proliferation, migration, cell death, and immune cell recruitment, we concentrated on alterations in intracellular redox state following PB2 treatment in gastric cancer cells. Through metabolomic and transcriptomic screening, we identified pathways altered by PB2 in gastric cancer cells, focusing on oxidative stress related biological functions, which were further confirmed through <em>in vitro</em> and <em>in vivo</em> validation. The heightened oxidative levels resulting from PB2 treatment induce endoplasmic reticulum stress and promote apoptosis. Furthermore, PB2 enhances autophagic flux to increase cellular free iron and promote ferroptosis. All in all, our research provides a comprehensive perspective on the therapeutic potential of PB2 in treating gastric cancer, demonstrating its capacity to inhibit growth signals and induce oxidative stress-related cell death.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102642"},"PeriodicalIF":5.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768916","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

Circular RNA circSCMH1 regulates glycolysis to inhibit gastric cancer metastasis via miR-296–3p/HSPB7-GLUT3 axis 环状RNA circSCMH1通过miR-296-3p/HSPB7-GLUT3轴调控糖酵解抑制胃癌转移。

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-12-15 DOI: 10.1016/j.tranon.2025.102644

Yue Yang , Qiushuang Wang , Zhe Gong , Jinsi Chen , Ya’nan Yang , Liqin Zhao , Yujia Zhai , Ting Zhao , Wenfang Du , Jieyun Zhang , Weijian Guo

Metastasis is main reason leading to gastric cancer (GC) caused death. GC metastasis is known to be associated with complex factors, of which circular RNAs (circRNAs) become hot molecules recently. How to effectively select key molecules participating in GC metastasis is still needing to be resolved. Through next-generation sequencing, metastasis-driven circRNAs were selected by comparing cancer and para-cancer tissues from GC patients with different metastasis tendency. The biological function of circSCMH1 was identified in vivo and in vitro. Through luciferase reporter system and functional rescue test, the downstream microRNA and target gene were identified. Glucose uptake, lactic acid production and ATP production were detected to estimate glycolysis level. Moreover, 110 GC samples were collected and following clinical association analysis was conducted. circSCMH1 showed significantly lower expression in high-metastasis GC. circSCMH1 could suppress glycolysis to inhibit GC proliferation and metastasis in vivo and in vitro, and played its biological function through miR-296–3p/HSPB7-GLUT3 axis. circSCMH1 showed closely association with GC lymph node metastasis and prognosis. circSCMH1 could inhibit gastric cancer metastasis through regulating glycolysis via miR-296–3p/HSPB7-GLUT3 axis. circSCMH1 could become potential biomarker for GC lymph node metastasis and even therapeutic target in the future.

转移是导致胃癌死亡的主要原因。已知胃癌转移与复杂的因素相关，其中环状rna （circRNAs）是近年来研究的热点分子。如何有效选择参与胃癌转移的关键分子仍是有待解决的问题。通过下一代测序，通过比较不同转移倾向的胃癌患者的癌组织和癌旁组织，选择转移驱动的环状rna。在体内和体外鉴定了circSCMH1的生物学功能。通过荧光素酶报告系统和功能挽救试验，鉴定下游microRNA和靶基因。葡萄糖摄取、乳酸生成和ATP生成检测糖酵解水平。并采集了110份气相色谱样本，进行了临床相关性分析。circSCMH1在高转移性胃癌中的表达明显降低。circSCMH1可抑制糖酵解，在体内外抑制GC增殖和转移，并通过miR-296-3p/HSPB7-GLUT3轴发挥其生物学功能。circSCMH1与胃癌淋巴结转移及预后密切相关。circSCMH1可通过miR-296-3p/HSPB7-GLUT3轴调控糖酵解，从而抑制胃癌转移。circSCMH1可能成为胃癌淋巴结转移的潜在生物标志物，甚至是未来的治疗靶点。

{"title":"Circular RNA circSCMH1 regulates glycolysis to inhibit gastric cancer metastasis via miR-296–3p/HSPB7-GLUT3 axis","authors":"Yue Yang , Qiushuang Wang , Zhe Gong , Jinsi Chen , Ya’nan Yang , Liqin Zhao , Yujia Zhai , Ting Zhao , Wenfang Du , Jieyun Zhang , Weijian Guo","doi":"10.1016/j.tranon.2025.102644","DOIUrl":"10.1016/j.tranon.2025.102644","url":null,"abstract":"<div><div>Metastasis is main reason leading to gastric cancer (GC) caused death. GC metastasis is known to be associated with complex factors, of which circular RNAs (circRNAs) become hot molecules recently. How to effectively select key molecules participating in GC metastasis is still needing to be resolved. Through next-generation sequencing, metastasis-driven circRNAs were selected by comparing cancer and para-cancer tissues from GC patients with different metastasis tendency. The biological function of circSCMH1 was identified in vivo and in vitro. Through luciferase reporter system and functional rescue test, the downstream microRNA and target gene were identified. Glucose uptake, lactic acid production and ATP production were detected to estimate glycolysis level. Moreover, 110 GC samples were collected and following clinical association analysis was conducted. circSCMH1 showed significantly lower expression in high-metastasis GC. circSCMH1 could suppress glycolysis to inhibit GC proliferation and metastasis in vivo and in vitro, and played its biological function through miR-296–3p/HSPB7-GLUT3 axis. circSCMH1 showed closely association with GC lymph node metastasis and prognosis. circSCMH1 could inhibit gastric cancer metastasis through regulating glycolysis via miR-296–3p/HSPB7-GLUT3 axis. circSCMH1 could become potential biomarker for GC lymph node metastasis and even therapeutic target in the future.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102644"},"PeriodicalIF":5.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145769320","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