Molecular Oncology最新文献_第2页

Spatial biology in cancer epigenetics. 癌症表观遗传学中的空间生物学。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-10-01 Epub Date: 2026-07-23 DOI: 10.1002/1878-0261.70310

Eva Crespo-García, Manel Esteller

{"title":"Spatial biology in cancer epigenetics.","authors":"Eva Crespo-García, Manel Esteller","doi":"10.1002/1878-0261.70310","DOIUrl":"10.1002/1878-0261.70310","url":null,"abstract":"Cancer develops inside organized tissue environments wherein cellular behavior is heavily influenced by local interactions and spatially restricted regulatory programs. While bulk and single-cell sequencing technologies have fundamentally revolutionized our understanding of tumor biology, these techniques often disrupt tissue architecture and therefore fail to capture the spatial context in which molecular processes occur. Spatial transcriptomics has provided important insights into tumor heterogeneity, microenvironmental organization, and cell-to-cell communication. However, gene expression alone offers only an indirect view of the regulatory mechanisms governing cellular states. The emergence of spatial epigenomic technologies now enables the investigation of chromatin accessibility, histone modifications, and DNA methylation while preserving tissue structure. Here, we discuss the current landscape of spatial epigenomics, including spatial ATAC-seq, spatial CUT&Tag, emerging spatial CUT&RUN approaches, spatial DNA methylation profiling, and multimodal strategies integrating epigenetic, transcriptional, and proteomic information within the same tissue context. Despite remaining technical and computational challenges, continued advances are expected to establish spatial epigenomics as a powerful tool for studying cancer pathways and their regulation within intact tissues.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2393-2409"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562495","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

Unraveling the epigenetic code in cancer cell-tumor microenvironment crosstalk. 揭示癌细胞-肿瘤微环境串扰中的表观遗传密码。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-10-01 Epub Date: 2026-08-25 DOI: 10.1002/1878-0261.70321

Ji Hoon Park, Mi-Young Kim

{"title":"Unraveling the epigenetic code in cancer cell-tumor microenvironment crosstalk.","authors":"Ji Hoon Park, Mi-Young Kim","doi":"10.1002/1878-0261.70321","DOIUrl":"10.1002/1878-0261.70321","url":null,"abstract":"Epigenetics plays a central role in cancer development and progression by governing the expression of genes involved in these processes. Accumulating evidence strongly indicates that these mechanisms not only alter cancer cell-intrinsic properties but also mediate reciprocal interactions between cancer cells and the tumor microenvironment (TME). In the context of cancer cell-intrinsic changes, epigenetic alterations contribute to cancer cell plasticity by regulating stemness, cell state transitions, and therapy resistance. In addition, epigenetic changes are a key driver of the establishment of a tumor-supportive environment by modifying the states of TME components, including fibroblasts, macrophages, and myeloid-derived suppressor cells. Epigenetic reprogramming in cancer cells and TME components is often induced by factors such as hypoxia and the secretion of exosomal long noncoding RNAs (lncRNAs), cytokines, and metabolites. In this review, we discuss various epigenetic mechanisms controlling cancer cell-intrinsic states, cancer cell-TME crosstalk, current epigenetic therapies, and future research directions that may lead to the discovery of new biomarkers and the development of effective epigenetic anticancer therapeutics.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2510-2532"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813655","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

Translating whole-genome doubling into precision medicine in cancer. 将全基因组加倍转化为癌症的精准医疗。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-10-01 Epub Date: 2026-07-12 DOI: 10.1002/1878-0261.70302

Sejung Lee, Junghyeok Lim, Jinhyuk Bhin

引用次数: 0

Epigenetic heterogeneity and plasticity in therapy-induced tumor states through single-cell multi-omics. 通过单细胞多组学研究治疗诱导肿瘤状态的表观遗传异质性和可塑性。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-10-01 Epub Date: 2026-06-04 DOI: 10.1002/1878-0261.70285

Hee Jung Kim, Hwiyeong Lee, Jin Hong, Daechan Park

{"title":"Epigenetic heterogeneity and plasticity in therapy-induced tumor states through single-cell multi-omics.","authors":"Hee Jung Kim, Hwiyeong Lee, Jin Hong, Daechan Park","doi":"10.1002/1878-0261.70285","DOIUrl":"10.1002/1878-0261.70285","url":null,"abstract":"Therapeutic resistance and disease recurrence remain major unresolved challenges in oncology, primarily driven by tumor heterogeneity and the inherent plasticity of cancer cells. Although multiple biological mechanisms contribute to these processes, epigenetic mechanisms are the key regulators of clonal diversification and adaptive transcriptional reprogramming under treatment pressure. This regulatory layer operates through reversible transcriptional changes that are independent of DNA sequence alterations, enabling cancer cells to respond to a selective environment. Recent advances in analytical methodologies, particularly single-cell multi-omics approaches, have markedly improved our capacity to dissect these regulatory processes at a single-cell resolution. This review explores how diverse therapeutics, including chemotherapy, targeted agents, immunotherapy, hormonal interventions, and epigenetic drugs, induce the widespread remodeling of DNA methylation patterns, histone modifications, and chromatin accessibility. These therapy-induced molecular changes drive transitions to distinct cellular states that confer survival advantages such as drug-tolerant persister (DTP) phenotypes, senescence-like populations, epithelial-mesenchymal transition (EMT) states, and immune-evasive cell populations. We further evaluated the current single-cell multi-omics platforms for profiling chromatin-based plasticity and identifying biomarkers with direct clinical relevance. Finally, we discuss how integrative multi-layer analyses enable comprehensive characterization of tumor-state evolution, providing a conceptual framework for precision oncology strategies aimed at overcoming resistance.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2424-2448"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148157139","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

Single-cell DNA methylation profiling: Technologies, computation, and applications in precision oncology. 单细胞DNA甲基化分析：技术、计算和精确肿瘤学应用。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-10-01 Epub Date: 2026-07-10 DOI: 10.1002/1878-0261.70303

Ik Soo Kim

{"title":"Single-cell DNA methylation profiling: Technologies, computation, and applications in precision oncology.","authors":"Ik Soo Kim","doi":"10.1002/1878-0261.70303","DOIUrl":"10.1002/1878-0261.70303","url":null,"abstract":"Cancer is an intrinsically heterogeneous disease characterized by distinct malignant subclones defined by specific genetic and epigenetic alterations, such as aberrant DNA methylation. Traditional bulk sequencing methods analyze large populations of cells in aggregate, yielding an averaged methylome signal that masks the rare but clinically significant epigenetic patterns driving tumor initiation, metastasis, and therapeutic resistance. The emergence of single-cell DNA methylation (scDNAme) sequencing has driven a paradigm shift in oncology by providing the resolution required to dissect this intratumoral heterogeneity. By profiling the epigenome of individual cells, scDNAme analysis enables the discovery of novel aberrant patterns, the precise reconstruction of cellular lineages, and the characterization of specific populations-such as cancer stem cells (CSCs) or drug-resistant clones-that possess distinct methylome signatures. This technological advance is not merely an incremental improvement; it is a prerequisite for understanding core cancer hallmarks, such as the evasion of growth control and resistance to apoptosis, which are frequently governed by these specific subclones. This review specifically provides a comprehensive comparative overview evaluating the technical and chemical capabilities of emerging single-cell modalities to distinguish DNA methylation profiles. By highlighting the strategic workflows of these emergent technologies alongside advanced computational tools, we emphasize how resolving these discrete cytosine variants empowers precise cell lineage tracing, the identification of refractory clones, and the implementation of locus-specific epigenetic editing therapies against causal tumor subclones.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2410-2423"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422513","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

ADP-ribosylation: An emerging regulator of the epigenome. adp核糖基化：一个新兴的表观基因组调控因子。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-10-01 Epub Date: 2026-08-10 DOI: 10.1002/1878-0261.70317

Cristel V Camacho, Chenqian Liu, W Lee Kraus

{"title":"ADP-ribosylation: An emerging regulator of the epigenome.","authors":"Cristel V Camacho, Chenqian Liu, W Lee Kraus","doi":"10.1002/1878-0261.70317","DOIUrl":"10.1002/1878-0261.70317","url":null,"abstract":"ADP-ribosylation (ADPRylation) is a post-translational modification best known for its roles in DNA damage responses and cytoplasmic signaling, but it also serves important functions in epigenome regulation. In the nucleus, ADPRylation modulates chromatin structure and gene expression through the coordinated modification of histones and chromatin-associated proteins. Although poly(ADP-ribosyl)ation (PARylation) has dominated the field, particularly as therapeutic targets in DNA repair deficient malignancies, a gap remains in our understanding of how mono(ADP-ribosyl)ation (MARylation)-mediated by mono(ADP-ribosyl) transferases (MARTs)-functions as a discrete, site-specific epigenomic mark. Nuclear MART-mediated ADPRylation modulates the activity, localization, and complex assembly of epigenomic enzymes, and directly modifies histones to influence chromatin accessibility and transcriptional dynamics. These reversible modifications intersect with canonical epigenomic marks, enabling rapid, context-dependent control of gene expression. Emerging studies further implicate dysregulated nuclear ADPRylation in cancer, where altered MARylation of chromatin regulators and transcription factors contributes to aberrant gene expression programs and may represent a novel class of therapeutic vulnerabilities. In this review, we synthesize emerging insights into nuclear ADPRylation, with a focus on MART-mediated regulation of histones and chromatin enzymes, and discuss how this regulatory layer expands current models of epigenomic control in physiology and how its alterations drive oncogenesis, offering novel, nonsynthetically lethal avenues for targeted cancer therapy.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2449-2465"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13458310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706885","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

Mutant p53^R273H disrupts PDPK1 homodimerization and contributes to PDPK1 activation. 突变体p53R273H破坏PDPK1二聚体并促进PDPK1激活。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-09-29 DOI: 10.1002/1878-0261.70341

Mei Chee Lim, Alvin Kunyao Guo, Yoko Itahana, Srinivasaraghavan Kannan, Valerie Goh, Mingmin Ong, Terina Yan Wen Tay, Weiying Ye, Sabhashina Radha Krishnan, Jun Nishiyama, Chandra S Verma, Koji Itahana

{"title":"Mutant p53R273H disrupts PDPK1 homodimerization and contributes to PDPK1 activation.","authors":"Mei Chee Lim, Alvin Kunyao Guo, Yoko Itahana, Srinivasaraghavan Kannan, Valerie Goh, Mingmin Ong, Terina Yan Wen Tay, Weiying Ye, Sabhashina Radha Krishnan, Jun Nishiyama, Chandra S Verma, Koji Itahana","doi":"10.1002/1878-0261.70341","DOIUrl":"10.1002/1878-0261.70341","url":null,"abstract":"The tumor suppressor p53 protein is frequently mutated in cancer, conferring oncogenic gain-of-function properties. One such mutant, p53R273H, is known to promote the activation of the PI3K/AKT pathway, but the underlying mechanism is unclear. Here, we demonstrated a direct interaction between p53R273H and 3-phosphoinositide-dependent protein kinase 1 (PDPK1), an upstream kinase of AKT. Interestingly, this interaction was unique to p53R273H, as it was not seen with wild-type p53 or other hotspot mutants such as p53R175H and p53R248W. Mechanistically, our in silico analysis revealed that the R273H mutation exposed a hydrophobic region within the p53R273H DNA-binding domain (DBD), facilitating PDPK1 binding. This binding disrupted PDPK1 homodimerization, a known inhibitory mechanism of PDPK1 activity. In contrast, the PDPK1-binding deficient mutant p53F270A/R273H did not disrupt PDPK1 homodimerization. We propose that p53R273H promotes AKT phosphorylation, potentially by enhancing PDPK1 homodimer dissociation. Supporting this, the small molecule PRIMA-1Met disrupted the p53R273H-PDPK1 interaction, resulting in reduced AKT phosphorylation. These findings highlight a new gain-of-function role of p53R273H, suggesting that targeting the p53R273H-PDPK1 interaction with PRIMA-1Met could dampen AKT phosphorylation in p53R273H-expressing cancers.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075410","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

NAPRT loss promotes lung tumor initiation and growth through AKT signaling independently of NAD⁺ biosynthesis. NAPRT缺失通过AKT信号传导促进肺肿瘤的发生和生长，而不依赖于NAD+的生物合成。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-09-25 DOI: 10.1002/1878-0261.70330

Myung Joon Oh, Ji Yun Jang, Yoon Jeon, Gi-Cheon Kim, Hwanho Lee, Jooyoung Lee, Ju-Hwa Kim, Hakhyun Kim, Minjee Kim, Ho-Keun Kwon, Ho Lee, Hyun Seok Kim

{"title":"NAPRT loss promotes lung tumor initiation and growth through AKT signaling independently of NAD+ biosynthesis.","authors":"Myung Joon Oh, Ji Yun Jang, Yoon Jeon, Gi-Cheon Kim, Hwanho Lee, Jooyoung Lee, Ju-Hwa Kim, Hakhyun Kim, Minjee Kim, Ho-Keun Kwon, Ho Lee, Hyun Seok Kim","doi":"10.1002/1878-0261.70330","DOIUrl":"10.1002/1878-0261.70330","url":null,"abstract":"Nicotinamide adenine dinucleotide (NAD+) metabolism is frequently rewired in cancer, creating metabolic vulnerabilities that can be therapeutically exploited. Loss of nicotinate phosphoribosyltransferase (NAPRT), a rate-limiting enzyme of the Preiss-Handler pathway, renders tumor cells dependent on nicotinamide phosphoribosyltransferase (NAMPT)-mediated NAD+ synthesis and serves as a predictive biomarker for NAMPT inhibitor sensitivity. However, whether NAPRT loss actively contributes to tumorigenesis remains unclear. Here, we show that NAPRT depletion promotes tumorigenic phenotypes in lung cancer through a noncanonical mechanism independent of NAD+ biosynthesis. NAPRT knockdown enhanced clonogenic initiation, sphere formation, and invasive capacity. Mechanistically, NAPRT loss drives mTORC2-dependent activation of the AKT signaling axis. This effect was not reversed by nicotinic acid or NAD+ supplementation or recapitulated by catalytic inhibition of NAPRT, indicating a function distinct from its metabolic role. Pharmacologic AKT inhibition attenuated the enhanced growth induced by NAPRT depletion. In vivo, lung-specific Naprt deletion significantly increased tumor burden in KrasG12D-driven mice without altering tumor histology or immune cell composition. Together, these findings identify a previously unrecognized tumor-suppressive role for NAPRT in lung tumor initiation and growth.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13613957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040052","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

Cancer-associated mutations in endometriosis reframe a benign disease through molecular oncology. 子宫内膜异位症的癌症相关突变通过分子肿瘤学重新定义了一种良性疾病。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-09-23 DOI: 10.1002/1878-0261.70295

Clarissa Mujacic, Maria Concetta Vitale, Rita Siino, Emilia Di Giovanni, Carla Ferrante Bannera, Enrico Di Marco, Andrea Gottardo, Tancredi Didier Bazan Russo, Nadia Barraco, Alessandro Perez, Valerio Gristina, Antonio Galvano, Giuseppe Badalamenti, Antonio Russo, Viviana Bazan, Lorena Incorvaia

{"title":"Cancer-associated mutations in endometriosis reframe a benign disease through molecular oncology.","authors":"Clarissa Mujacic, Maria Concetta Vitale, Rita Siino, Emilia Di Giovanni, Carla Ferrante Bannera, Enrico Di Marco, Andrea Gottardo, Tancredi Didier Bazan Russo, Nadia Barraco, Alessandro Perez, Valerio Gristina, Antonio Galvano, Giuseppe Badalamenti, Antonio Russo, Viviana Bazan, Lorena Incorvaia","doi":"10.1002/1878-0261.70295","DOIUrl":"10.1002/1878-0261.70295","url":null,"abstract":"Endometriosis is a benign yet debilitating condition, and its molecular complexity remains unexplored. Although clinically recognized, its genetic landscape has long been overlooked. This review analyses cancer-associated mutations (CAMs) identified in endometriotic lesions, revealing parallels with malignancy. Recurrent mutations in key oncogenic and tumour suppressor genes-PIK3CA, CTNNB1, KRAS, PTEN and ARID1A-emerge with patterns distinct from cancer, yet suggesting shared mechanisms. Despite the limited genomic data, these findings position endometriosis as a valuable model for investigating early tumour-like processes. By reframing endometriosis through the lens of molecular oncology, this study offers new insights into its pathogenesis and proposes a translational framework for advancing diagnostics and understanding disease progression at the benign-malignant interface.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024146","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

Extracellular matrix remodeling and immune reprogramming drive residual tumor progression of liver cancer after incomplete microwave ablation. 细胞外基质重塑和免疫重编程驱动肝癌不完全微波消融后残余肿瘤的进展。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-09-22 DOI: 10.1002/1878-0261.70337

Yu Liu, Yubei He, Nikolaus Berndt, Michael Mülleder, Kathrin Textoris-Taube, Jing Guo, Matthias Stechele, Justus Ramtke, Shraga Nahum Goldberg, Lynn Jeanette Savic

{"title":"Extracellular matrix remodeling and immune reprogramming drive residual tumor progression of liver cancer after incomplete microwave ablation.","authors":"Yu Liu, Yubei He, Nikolaus Berndt, Michael Mülleder, Kathrin Textoris-Taube, Jing Guo, Matthias Stechele, Justus Ramtke, Shraga Nahum Goldberg, Lynn Jeanette Savic","doi":"10.1002/1878-0261.70337","DOIUrl":"10.1002/1878-0261.70337","url":null,"abstract":"Although microwave ablation (MWA) constitutes an effective targeted treatment for liver cancer, the mechanisms driving high recurrence rates remain poorly understood. To elucidate these processes, we established an incomplete MWA (iMWA) model in rabbit VX2 tumors and conducted proteomic profiling of residual tumors at Days 3 (D3) and 14 (D14) postablation. By integrating genomic profiles from mouse radiofrequency ablation (RFA) models, we identified 81 and 92 upregulated proteins at D3 and D14, respectively. Functional enrichment analysis (STRING and Enrichr) revealed acute injury response and extracellular matrix (ECM) remodeling predominating at D3, then markedly declining by D14. Conversely, pathways associated with signal transduction, tumorigenesis, and immune pathways were substantially upregulated at D14. Specifically, protein-protein interaction (PPI) analysis revealed that macrophage remodeling and immune checkpoint networks are functionally coupled at D14 to orchestrate an immunosuppressive microenvironment. Stouffer analysis confirmed the shift from matrix remodeling at an early stage to late-stage oncogenic signal transduction and immune suppression at progression. Overall, these findings characterize the dynamic mechanisms of postablation residual tumor growth and highlight potential therapeutic targets to inhibit protumorigenic pathways while enhancing antitumor immunity.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025224","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