Translational Oncology最新文献_第6页

Corrigendum to “A Clinical Study on the Efficacy of Concurrent Chemoradiotherapy Combined with Targeted Therapy and Hyperthermia in Patients with Locally Advanced Cervical Cancer” [Translational Oncology,Volume61, November 2025, 102516] “同步放化疗联合靶向治疗和热疗治疗局部晚期宫颈癌疗效的临床研究”的勘误表[转化肿瘤学，vol . 61，十一月2025,102516]

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2026-02-01 Epub Date: 2025-12-30 DOI: 10.1016/j.tranon.2025.102656

Yuhan Jia , Feng Zhang , Kun Zou , Lijuan Zou

引用次数: 0

NTRK2 promotes malignant progression and paclitaxel resistance of lung adenocarcinoma through targeting MYC/ABCF1 axis NTRK2通过靶向MYC/ABCF1轴促进肺腺癌的恶性进展和紫杉醇耐药。

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2026-02-01 Epub Date: 2026-01-06 DOI: 10.1016/j.tranon.2025.102655

Rongrong Cui , Yuanyuan Wang , Yao Yao , Xiaojuan Ren , Yuchen Zhang , Daxu Li , Peng Hou , Meiju Ji , Yiping Qu

Lung adenocarcinoma (LUAD) is the most prevalent histological subtype of lung cancer, and the development of chemoresistance often leads to tumor recurrence and metastasis. Neurotrophic receptor tyrosine kinase 2 (NTRK2) has been implicated in tumorigenesis and chemotherapy resistance, but its precise role in LUAD and contribution to paclitaxel resistance remain unclear. In this study, we found that NTRK2 expression was significantly upregulated in LUADs compared with paired noncancerous tissues and was further elevated in samples from patients who experienced recurrence following paclitaxel-based chemotherapy. Functional assays demonstrated that NTRK2 knockdown markedly inhibited the malignant phenotypes of LUAD cells in vitro and significantly restored the sensitivity of LUAD cells to paclitaxel. Conversely, NTRK2 overexpression promoted cell proliferation, colony formation, and reduced responsiveness to paclitaxel. Consistently, in vivo xenograft experiments revealed that NTRK2 knockdown suppressed tumor growth and enhanced the antitumor efficacy of paclitaxel. Mechanistically, NTRK2 activated the MAPK/ERK and PI3K/AKT signaling pathways, leading to the upregulation of MYC, which in turn directly activated the transcription of ATP-binding cassette subfamily F member 1 (ABCF1), thereby promoting LUAD progression and paclitaxel resistance. Collectively, our findings identify NTRK2 as a critical oncogenic driver that confers chemoresistance by activating the NTRK2/MYC/ABCF1 signaling axis. This study provides new mechanistic insights into the regulation of paclitaxel resistance in LUAD and highlights NTRK2 and its downstream effectors as promising therapeutic targets for overcoming chemoresistance.

肺腺癌（LUAD）是肺癌最常见的组织学亚型，化疗耐药的发展往往导致肿瘤的复发和转移。神经营养受体酪氨酸激酶2 （NTRK2）与肿瘤发生和化疗耐药有关，但其在LUAD中的确切作用和对紫杉醇耐药的贡献尚不清楚。在这项研究中，我们发现与配对的非癌组织相比，LUADs中的NTRK2表达显著上调，并且在紫杉醇化疗后复发的患者样本中进一步升高。功能实验表明，NTRK2敲低可显著抑制LUAD细胞的恶性表型，并显著恢复LUAD细胞对紫杉醇的敏感性。相反，NTRK2过表达促进细胞增殖、集落形成，并降低对紫杉醇的反应性。与此一致的是，体内异种移植实验显示，NTRK2敲低抑制肿瘤生长，增强紫杉醇的抗肿瘤功效。机制上，NTRK2激活MAPK/ERK和PI3K/AKT信号通路，导致MYC上调，进而直接激活atp结合盒亚家族F成员1 （ABCF1）的转录，从而促进LUAD进展和紫杉醇耐药。总的来说，我们的研究结果确定NTRK2是一个关键的致癌驱动因素，通过激活NTRK2/MYC/ABCF1信号轴来赋予化学耐药。该研究为LUAD中紫杉醇耐药的调控提供了新的机制见解，并强调了NTRK2及其下游效应物是克服化疗耐药的有希望的治疗靶点。

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引用次数: 0

Interleukin 35 promotes progression of hepatocellular carcinoma by recruiting neutrophils 白细胞介素35通过募集中性粒细胞促进肝细胞癌的进展。

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2026-02-01 Epub Date: 2026-01-06 DOI: 10.1016/j.tranon.2025.102630

Wei Gan , Guo-Qiang Sun , Jin-Long Huang , Bao-Ye Sun , Zhu-Tao Wang , Zhang-Fu Yang , Cheng Zhou , Yong Yi , Shuang-Jian Qiu

Background

A growing number of therapeutic strategies against hepatocellular carcinoma (HCC) have emerged. However, their efficacy remains limited. This study investigated the mechanism of interleukin-35 (IL-35) in the progression of HCC and its potential application in HCC treatment.

Methods

The expression of IL-35,Gp130 ,IL12-Rβ2, CCL3,etc. in HCC tissues was detected by immunohistochemistry(IHC), and the expression of IL-35 in HCC cell lines was detected by fluorescence assay. Kaplan-Meier survival analysis of IL-35 and its receptor in relation to overall survival(OS) and recurrence free survival(RFS) in patients with HCC. The mouse subcutaneous tumor models to study the effects of IL-35 on HCC growth and immune cells. Western blot were used to detect the expression IL-35, CCL3, FGF2, and flow cytometric plot were performed to explore the immune cells infiltration in the tumor tissue.

Results

High expression of IL-35 in patients with HCC was associated with poor prognosis. Furthermore, IL-35 could facilitate tumor progression by affecting neutrophil infiltration, angiogenesis, and CD8+ T-cell infiltration. Additionally, CCL3 was a key factor mediating the recruitment of neutrophils by IL-35. FGF2 derived from neutrophils stimulated by IL-35 promoted intratumoral angiogenesis. IL-35 also facilitated the adhesion of tumors to endothelial cells, with neutrophils further enhancing this effect both. Anti-IL-35 antibody combined with anti-PD1 antibody significantly enhanced which therapeutic effect in HCC.

Conclusions

Our data show that the high expression of IL-35 in patients with HCC is an important tumor promoter. Combined treatment with anti-IL-35 and anti-PD1 antibodies have potential therapeutic effect against HCC.

背景：针对肝细胞癌（HCC）的治疗策略越来越多。然而，它们的功效仍然有限。本研究旨在探讨白细胞介素-35 （IL-35）在HCC发生发展中的作用机制及其在HCC治疗中的潜在应用。方法：检测IL-35、Gp130、IL12-Rβ2、CCL3等的表达。免疫组化（IHC）法检测肝癌组织中IL-35的表达，荧光法检测肝癌细胞系中IL-35的表达。肝癌患者IL-35及其受体与总生存期（OS）和无复发生存期（RFS）的Kaplan-Meier生存分析建立小鼠皮下肿瘤模型，研究IL-35对肝癌生长及免疫细胞的影响。Western blot检测IL-35、CCL3、FGF2的表达，流式细胞术观察免疫细胞在肿瘤组织中的浸润情况。结果：肝癌患者IL-35高表达与预后不良相关。此外，IL-35可以通过影响中性粒细胞浸润、血管生成和CD8+ t细胞浸润来促进肿瘤进展。此外，CCL3是介导IL-35募集中性粒细胞的关键因子。IL-35刺激中性粒细胞产生的FGF2促进肿瘤内血管生成。IL-35还促进肿瘤与内皮细胞的粘附，中性粒细胞进一步增强了这一作用。抗il -35抗体联合抗pd1抗体可显著提高其治疗HCC的效果。结论：我们的数据表明，IL-35在HCC患者中高表达是一个重要的肿瘤启动子。联合抗il -35和抗pd1抗体治疗肝癌有潜在的治疗效果。

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引用次数: 0

Single‑cell mapping of neutrophil extracellular trap signatures in lung adenocarcinoma reveals immune landscapes, prognostic potential, and therapeutic targets 肺腺癌中性粒细胞胞外陷阱特征的单细胞定位揭示了免疫景观、预后潜力和治疗靶点。

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2026-02-01 Epub Date: 2026-01-06 DOI: 10.1016/j.tranon.2025.102651

Jingjie Liu , Kang Tian , Hui Shen , Lei Zhou , Subo Dong , Fuchun Huo , Jian Zhang

Neutrophil extracellular traps (NETs) have emerged as key modulators in the tumor microenvironment, yet their cellular heterogeneity, molecular mechanisms, and clinical relevance in lung adenocarcinoma (LUAD) remain elusive. Here, we performed an integrative single‑cell and multi‑omics dissection of NETs activity across LUAD tissues. Single‑cell transcriptomics revealed that NETs signatures were predominantly enriched in neutrophils but also detectable in dendritic cells and macrophages, where NETs‑high subpopulations exhibited intensified intercellular signaling. Genomic profiling indicated that NETs‑related genes were largely affected by missense mutations and single nucleotide polymorphisms (C > A and C > T), with frequent alterations in PTPRD, VCAN, and ZNF804A. Functional enrichment associated these genes with immune regulation and tumor‑promoting pathways. By integrating seven independent clinical cohorts, we constructed a machine‑learning–based NETs‑related prognostic signature (NETs‑Sig) that robustly predicted overall survival across datasets (AUC > 0.75). Patients with high NETs‑Sig scores exhibited immune‑cold phenotypes characterized by reduced immune infiltration and impaired antigen presentation, whereas low‑score cases displayed elevated MHC‑II expression, enhanced antigen processing, and putative sensitivity to immunotherapy. Experimental validation further identified AP2S1 as a central NETs‑Sig gene—overexpressed in multiple cancers and functionally promoting invasion and metastasis in LUAD cells. Together, our study delineates the cellular, genomic, and immunological frameworks of NETs in LUAD, establishes NETs‑Sig as a clinically actionable biomarker for risk stratification and immunotherapy guidance, and highlights AP2S1 as a promising therapeutic target for translational intervention.

中性粒细胞胞外陷阱（NETs）已成为肿瘤微环境中的关键调节剂，但其细胞异质性、分子机制和与肺腺癌（LUAD）的临床相关性仍不明确。在这里，我们对LUAD组织中的NETs活性进行了单细胞和多组学的综合解剖。单细胞转录组学显示，NETs特征主要富集在中性粒细胞中，但也可在树突状细胞和巨噬细胞中检测到，其中NETs高亚群表现出强化的细胞间信号传导。基因组分析表明，NETs相关基因在很大程度上受到错义突变和单核苷酸多态性（C > A和C > T）的影响，PTPRD、VCAN和ZNF804A基因频繁改变。功能富集将这些基因与免疫调节和肿瘤促进途径联系起来。通过整合七个独立的临床队列，我们构建了一个基于机器学习的NETs相关预后特征（NETs - Sig），该特征可靠地预测了各数据集的总生存期（AUC > 0.75）。NETs - Sig得分高的患者表现出免疫冷表型，其特征是免疫浸润减少和抗原呈递受损，而得分低的患者表现出MHC - II表达升高、抗原加工增强以及对免疫治疗的推定敏感性。实验验证进一步确定AP2S1是多种癌症中过表达的中心NETs - Sig基因，并在功能上促进LUAD细胞的侵袭和转移。总之，我们的研究描述了LUAD中NETs的细胞、基因组和免疫学框架，确立了NETs - Sig作为临床可操作的风险分层和免疫治疗指导的生物标志物，并强调了AP2S1作为翻译干预的有希望的治疗靶点。

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引用次数: 0

Mechanistic and translational insights into plant-derived natural products in preclinical multiple myeloma research: Current evidence 临床前多发性骨髓瘤研究中植物来源的天然产物的机制和转化见解：目前的证据

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2026-02-01 Epub Date: 2026-01-08 DOI: 10.1016/j.tranon.2026.102666

Lulu Li , Jie Xu , Liming Yu , Jingbo Shi , Changnian Li , Jiabao Gu , Yaru Wang , Siyuan Cui

Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of abnormal plasma cells, with marked heterogeneity and therapeutic refractoriness. Despite the introduction of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), monoclonal antibodies (mAbs), and chimeric antigen receptor T-cell (CAR-T) therapy, relapse and drug resistance remain major challenges that urgently need to be addressed. Plant-derived natural products have attracted increasing attention in recent years due to their multi-target synergistic effects, demonstrating unique potential in inducing MM cell apoptosis, reversing drug resistance, and modulating the immune microenvironment—making them a rising focus in translational medicine research. In this structured narrative review, we systematically summarize the anti-myeloma mechanisms of fourteen plant-derived natural products, including plant-derived monomeric compounds (baicalein, artemisinin, curcumin, celastrol, gambogic acid, resveratrol, ginsenosides, icariin, oridonin, plumbagin, formononetin) and standardized plant extracts (Strychnos nux-vomica root extract, dandelion flavonoids, Hedyotis diffusa polysaccharides). This review highlights their multi-target regulatory effects on signaling pathways, cell cycle modulation, and immune regulation, and further discusses their potential translational value in overcoming drug resistance and optimizing combination treatment strategies. Literature was retrieved from PubMed, Web of Science, and CNKI databases, covering studies published up to January 2025. Although plant-derived natural products exhibit promising multi-target regulatory mechanisms in MM therapy, their clinical translation remains limited by poor bioavailability of single compounds and the lack of standardized extracts. Future research should integrate systems pharmacology with clinical studies to elucidate multi-component synergistic networks and develop novel targeted formulations, thereby accelerating the efficient translation of phytochemicals from bench to bedside.

多发性骨髓瘤（MM）是一种以异常浆细胞克隆增生为特征的血液系统恶性肿瘤，具有明显的异质性和治疗难治性。尽管引入了蛋白酶体抑制剂（pi）、免疫调节药物（IMiDs）、单克隆抗体（mab）和嵌合抗原受体t细胞（CAR-T）治疗，但复发和耐药仍然是迫切需要解决的主要挑战。近年来，植物源性天然产物因其多靶点协同作用而受到越来越多的关注，在诱导MM细胞凋亡、逆转耐药、调节免疫微环境等方面显示出独特的潜力，成为转化医学研究的热点。在这篇结构化的叙述综述中，我们系统地总结了14种植物源性天然产物的抗骨髓瘤机制，包括植物源性单体化合物（黄芩素、青蒿素、姜黄素、celastrol、藤黄酸、白藜芦醇、人参皂苷、淫羊藿苷、冬凌草苷、白桦柄花素）和标准化植物提取物（马钱子根提取物、蒲公英黄酮、白花蛇耳草多糖）。本文综述了它们在信号通路、细胞周期调节和免疫调节等方面的多靶点调控作用，并进一步讨论了它们在克服耐药和优化联合治疗策略方面的潜在翻译价值。文献检索自PubMed、Web of Science和CNKI数据库，涵盖截至2025年1月发表的研究。尽管植物来源的天然产物在多发性骨髓瘤治疗中显示出有希望的多靶点调节机制，但它们的临床转化仍然受到单一化合物生物利用度差和缺乏标准化提取物的限制。未来的研究应将系统药理学与临床研究结合起来，阐明多组分协同网络，开发新的靶向制剂，从而加快植物化学物质从实验室到床边的有效转化。

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引用次数: 0

A serum-derived 3D tumor model platform for personalized prediction and monitoring of chemotherapeutic response in pancreatic ductal adenocarcinoma 一个血清衍生的三维肿瘤模型平台，用于个性化预测和监测胰腺导管腺癌的化疗反应。

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2026-02-01 Epub Date: 2026-01-06 DOI: 10.1016/j.tranon.2025.102659

Sara Cherradi , Salomé Roux , Marie Dupuy , Eric Assenat , Hong Tuan Duong

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal cancer, largely due to late diagnosis, tumor heterogeneity, and a dense, immunosuppressive stroma that limits therapeutic efficacy. While regimens like FOLFIRINOX and gemcitabine-based therapies offer some benefit, treatment selection remains empirical, with no reliable predictive models to guide personalized decisions. We adapted our previously validated serum-derived educated spheroid technology creating 3D spheroids using PDAC patient serum. These spheroids maintained structural integrity, viability, and consistent size over eight days, avoiding overgrowth. They also exhibited extracellular matrix deposition such as type I collagen, and expressed key genes involved in drug resistance and tumor progression including COL1A1, FN1, MMP2, CXCL1, and CXCL2. Using the Target-Independent Cell Killing (TICK) strategy, we established individualized chemograms to assess true therapeutic response helping clinicians in refining the optimal treatment protocol. In a 16-case study, our model achieved high concordance with clinical responses across gemcitabine, Gem-Pac, and FOLFIRINOX treatments supporting its utility in personalized care. Finally, we demonstrated that predictive accuracy was highest when patient serum was collected within a short window prior to treatment initiation. These findings support PDAC patient serum-educated spheroids as a rapid, non-invasive, and physiologically relevant tool for guiding personalized chemotherapy and monitoring treatment response in real time.

胰腺导管腺癌（PDAC）仍然是一种高致死率的癌症，主要原因是诊断较晚、肿瘤异质性和致密的免疫抑制间质限制了治疗效果。虽然像FOLFIRINOX和基于吉西他滨的治疗方案提供了一些好处，但治疗选择仍然是经验主义的，没有可靠的预测模型来指导个性化的决策。我们采用了先前验证的血清衍生的教育球体技术，使用PDAC患者血清创建3D球体。这些球体在8天的时间里保持了结构的完整性、活力和一致的大小，避免了过度生长。它们还表现出细胞外基质沉积，如I型胶原蛋白，并表达参与耐药和肿瘤进展的关键基因，包括COL1A1、FN1、MMP2、CXCL1和CXCL2。使用目标非依赖性细胞杀伤（TICK）策略，我们建立了个性化的化疗图来评估真正的治疗反应，帮助临床医生完善最佳治疗方案。在一项16例研究中，我们的模型与吉西他滨、Gem-Pac和FOLFIRINOX治疗的临床反应高度一致，支持其在个性化护理中的应用。最后，我们证明，在治疗开始前的短时间内收集患者血清时，预测准确性最高。这些发现支持PDAC患者血清教育球体作为一种快速、无创和生理相关的工具，用于指导个性化化疗和实时监测治疗反应。

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引用次数: 0

Integrated spatial and single-cell transcriptomics reveals RPL8 as a prognostic biomarker and therapeutic target in hepatocellular carcinoma 综合空间和单细胞转录组学显示RPL8是肝细胞癌的预后生物标志物和治疗靶点。

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2026-02-01 Epub Date: 2026-01-06 DOI: 10.1016/j.tranon.2025.102663

Jinna Tan , Junzhu Liang , Yaoyang Li , Jiaqian He , Hui Yin , Hemeng Wu , Yuzhen Luo , Mingfen Li , Fuli Long , Hongsheng Lin

Background & aims

Ribosomal protein L8 (RPL8) is up-regulated in hepatocellular carcinoma (HCC), yet its clinical value and microenvironment role remain unclear.

Methods

Multi-omics (TCGA, CPTAC), scRNA-seq (GSE146115) and spatial transcriptomics were integrated; function was tested by RPL8 knockdown, proliferation/migration assays and drug-sensitivity screens.

Results

RPL8 mRNA/protein were markedly elevated (p < 0.001) with AUC 0.95 for diagnosis. High RPL8 independently predicted shorter overall (HR 1.42) and disease-specific survival (HR 1.35). Mechanistically, RPL8 co-activated MYC/G2M signaling, rewired glutathione metabolism and correlated with cell-cycle/DNA-repair scores (p < 0.001). scRNA-seq showed selective RPL8 enrichment in malignant hepatocytes and exhausted CD8⁺ T cells; spatial maps revealed tumor-confined expression inversely linked to immune infiltration (p < 0.01). Silencing RPL8 suppressed proliferation, migration and glutathione synthesis (p < 0.001), while sensitizing cells to sirolimus and sclareol (p < 0.05).

Conclusions

RPL8 drives HCC progression and immune evasion, qualifying it as a diagnostic biomarker and therapeutic target.

背景与目的：核糖体蛋白L8 （RPL8）在肝细胞癌（HCC）中表达上调，但其临床价值和微环境作用尚不清楚。方法：整合多组学（TCGA、CPTAC）、scRNA-seq （GSE146115）和空间转录组学；通过RPL8敲除、增殖/迁移试验和药敏筛选检测功能。结果：RPL8 mRNA/蛋白显著升高（p < 0.001），诊断AUC为0.95。高RPL8独立预测较短的总生存率（HR 1.42）和疾病特异性生存率（HR 1.35）。在机制上，RPL8共同激活MYC/G2M信号，重新连接谷胱甘肽代谢，并与细胞周期/ dna修复评分相关（p < 0.001）。scRNA-seq显示，RPL8在恶性肝细胞和耗尽CD8+T细胞中选择性富集；空间图显示肿瘤受限表达与免疫浸润呈负相关（p < 0.01）。沉默RPL8抑制细胞增殖、迁移和谷胱甘肽合成（p < 0.001），同时使细胞对西罗莫司和巩膜醇敏感（p < 0.05）。结论：RPL8驱动HCC进展和免疫逃避，使其成为一种诊断生物标志物和治疗靶点。

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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 : 2026-02-01 Epub 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。

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引用次数: 0

MAZ-Mediated ubiquitin-conjugating enzyme E2C upregulation promotes breast cancer progression via the MAPK signaling pathway maz介导的泛素偶联酶E2C上调通过MAPK信号通路促进乳腺癌进展。

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2026-02-01 Epub Date: 2026-01-06 DOI: 10.1016/j.tranon.2025.102646

Jinhui Bai , Mei Deng , Xueting Wu , Chao Xiong , Huixian Wu , Li Wang , Jie Qin

Background

Malignant proliferation and invasion of tumor cells are the primary causes of death among patients with breast cancer, yet the molecular mechanisms orchestrating cancer metastasis are not well elucidated. Ubiquitin-conjugating enzyme E2C (UBE2C) has been reported to be involved in the tumorigenesis and development of various malignant tumors; however, the biological roles and underlying mechanisms of UBE2C in breast cancer remain unclear.

Methods

UBE2C expression was analyzed in breast cancer tissue and cell lines using immunohistochemistry, quantitative reverse transcription PCR (RT-qPCR) and Western blot. The biological roles of UBE2C and its transcription factor MAZ were investigated in vitro using CCK-8, plate cloning, scratch, Transwell, cell cycle and apoptosis assays, while a nude mouse subcutaneous tumorigenic model was employed for the in vivo studies. Dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were conducted to validate the binding relationship between MAZ and UBE2C.

Results

UBE2C expression is elevated in breast cancer, and higher levels of UBE2C are associated with poorer survival among patients with breast cancer. UBE2C promotes the progression of breast cancer both in vivo and in vitro. Additionally, UBE2C is a direct transcriptional target of MAZ, which also accelerates malignant development of breast cancer. Furthermore, UBE2C exerts its oncogenic effects dependent on the MAPK signaling pathway.

Conclusion

Our findings highlight the critical role of the MAZ/UBE2C/MAPK signaling axis in the progression of breast cancer and identify potential novel therapeutic targets for its treatment.

背景：肿瘤细胞的恶性增殖和侵袭是乳腺癌患者死亡的主要原因，但调控肿瘤转移的分子机制尚不清楚。据报道，泛素偶联酶E2C （UBE2C）参与多种恶性肿瘤的发生和发展；然而，UBE2C在乳腺癌中的生物学作用和潜在机制尚不清楚。方法：采用免疫组织化学、定量反转录PCR （RT-qPCR）和Western blot技术分析乳腺癌组织和细胞系中UBE2C的表达。采用CCK-8法、平板克隆法、scratch法、Transwell法、细胞周期法和细胞凋亡法研究UBE2C及其转录因子MAZ在体外的生物学作用，并采用裸鼠皮下致瘤模型进行体内研究。通过双荧光素酶报告基因实验和染色质免疫沉淀（ChIP）实验验证MAZ与UBE2C的结合关系。结果：UBE2C在乳腺癌中表达升高，且UBE2C水平升高与乳腺癌患者较差的生存率相关。UBE2C在体内和体外均促进乳腺癌的进展。此外，UBE2C是MAZ的直接转录靶点，也加速了乳腺癌的恶性发展。此外，UBE2C依赖于MAPK信号通路发挥其致癌作用。结论：我们的研究结果强调了MAZ/UBE2C/MAPK信号轴在乳腺癌进展中的关键作用，并确定了潜在的新治疗靶点。

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引用次数: 0

Single-cell analysis identifies a stemness-associated tumor cell subpopulation and develops a prognostic scoring model in esophageal squamous cell carcinoma 单细胞分析确定了一个干细胞相关的肿瘤细胞亚群，并在食管鳞状细胞癌中建立了一个预后评分模型。

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2026-02-01 Epub Date: 2026-01-06 DOI: 10.1016/j.tranon.2025.102653

Wei Ye , Wei Su , Chang Lei , Chenjun Huang , Mingjun Du

Esophageal squamous cell carcinoma (ESCC) exhibits marked heterogeneity and poor prognosis, but the contribution of stemness‑related tumor cells remains unclear. Using single‑cell RNA sequencing, we identified eight tumor subpopulations in ESCC, among which one cluster displayed prominent stem‑like and proliferative features with high expression of MKI67, STMN1, and UBE2C. Based on its marker genes, we established a stemness‑associated scoring model (SASM). Validation in independent TCGA and GSE53624 cohorts confirmed that higher SASM scores predicted shorter overall survival and reduced immune infiltration, particularly of CD8⁺ T cells. SASM scores were positively correlated with tumor mutational burden (TMB), and patients with high SASM and low TMB exhibited the poorest outcomes. Further analysis identified TFDP1 as a key gene associated with SASM and adverse prognosis, which was upregulated in tumor tissues and promoted ESCC cell proliferation in vitro. Overall, our study delineates stemness‑related tumor heterogeneity in ESCC, proposes a prognostic scoring system with immunological relevance, and highlights TFDP1 as a potential therapeutic target.

食管鳞状细胞癌（ESCC）具有明显的异质性和较差的预后，但与干性相关的肿瘤细胞的作用尚不清楚。通过单细胞RNA测序，我们在ESCC中鉴定出8个肿瘤亚群，其中一个亚群表现出突出的干细胞样和增殖特征，MKI67、STMN1和UBE2C高表达。基于其标记基因，我们建立了茎干相关评分模型（SASM）。在独立的TCGA和GSE53624队列中的验证证实，较高的SASM评分预示着更短的总生存期和更少的免疫浸润，尤其是CD8 + T细胞。SASM评分与肿瘤突变负荷（TMB）呈正相关，SASM高、TMB低的患者预后最差。进一步分析发现TFDP1是与SASM及不良预后相关的关键基因，在肿瘤组织中表达上调，促进体外ESCC细胞增殖。总的来说，我们的研究描述了ESCC中与干细胞相关的肿瘤异质性，提出了一种具有免疫学相关性的预后评分系统，并强调了TFDP1是一个潜在的治疗靶点。

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