Oncology Research最新文献

{"title":"OTUD7B Stabilization by METTL14-Mediated m6A Methylation Drives HIF-1<b>α</b> Expression in Esophageal Squamous Cell Carcinoma.","authors":"Fei Ren, Yansen Cai, Yang Song","doi":"10.32604/or.2025.061301","DOIUrl":"10.32604/or.2025.061301","url":null,"abstract":"<p><strong>Objectives: </strong>Epigenetic changes, particularly N6-methyladenosine (m6A) modifications, play a pivotal role in cancer development. This study explored the role of ovarian tumor deubiquitinase 7B (OTUD7B) in esophageal squamous cell carcinoma (ESCC) in the context of m6A methylation and the hypoxia-inducible factor-1α (HIF-1α) pathway.</p><p><strong>Methods: </strong>The GSE179267 dataset was used to conduct differential gene expression analysis to identify key m6A-enriched genes. The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), and Sequence-based RNA Adenosine Methylation Site Predictor (SRAMP) databases were used to evaluate the expression of OTUD7B in ESCC and its correlation with methyltransferase-like 14 (METTL14) and HIF-1α. The m6A content in total RNA extracted from ESCC cells was assessed using a dot blot assay. Gene-specific m6A-PCR was used to quantify m6A modifications in OTUD7B mRNA. The functional role of OTUD7B was explored using clonogenic and Transwell assays. The effect of OTUD7B on HIF-1α ubiquitination was detected using a co-immunoprecipitation assay.</p><p><strong>Results: </strong>OTUD7B was identified as a pivotal m6A-driven oncogene correlated with METTL14 and HIF-1α. METTL14 enhanced the mRNA stability and expression of OTUD7B through m6A methylation. OTUD7B overexpression counteracted the inhibitory effects of METTL14 knockdown on cell proliferation and invasion and stabilized HIF-1α by promoting deubiquitination.</p><p><strong>Conclusion: </strong>METTL14 plays a crucial role in the stabilization of OTUD7B through m6A methylation, thereby inhibiting the ubiquitin-proteasomal degradation of HIF-1α in ESCC. These findings highlight the potential of targeting the METTL14-OTUD7B axis as a therapeutic strategy for ESCC.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 8","pages":"2055-2074"},"PeriodicalIF":4.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation of senescence-related gene FEN1 on neuroblastoma progression and cisplatin chemotherapy sensitivity.","authors":"Youyang Hu, Yishu Luo, Tianyue Xie, Yuehua Chen, Jun Zhao, Weichao Ji, Zhiwei Yan, Sitong Qiu, Kexin Gao, Haixia Zhu, Limin Ma, Qiyou Yin","doi":"10.32604/or.2025.060021","DOIUrl":"10.32604/or.2025.060021","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;Neuroblastoma (NB) is frequently associated with high-risk pediatric cases that demonstrate limited response to cisplatin, contributing to a poor prognosis. Recent studies have explored the role of tumor cell senescence in increasing sensitivity to this chemotherapy agent. This study aims to identify genes related to cell senescence in children diagnosed with NB, evaluate their influence on cisplatin sensitivity, and investigate potential strategies to enhance the efficacy of chemotherapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Gene expression profiles and clinical data were obtained for 498 NB patients from the GEO database (GSE49710). The study focused on identifying genes that were differentially expressed between stage IV and other stages, particularly those linked to cell senescence and cisplatin resistance. To analyze the prognostic significance of these differentially expressed genes, we employed LASSO regression and multivariate Cox proportional hazards models. Transcriptomic and proteomic analyses of 15 NB specimens revealed a significant correlation between Flap endonuclease-1 (FEN1) expression levels and both cellular senescence and sensitivity to cisplatin. We quantified FEN1 expression and cisplatin IC50 values in four different NB cell lines. The influence of FEN1 knockdown and overexpression on NB cell proliferation, invasion, and migration was evaluated using cloning assays, transwell assays, and scratch assays. Furthermore, we utilized Western blotting to analyze senescence-associated proteins p21 and proliferating cell nuclear antigen (PCNA), thereby evaluating the role of FEN1 in cellular senescence. The impact of FEN1 on cisplatin sensitivity was investigated via the CCK-8 cell counting assay. Additionally, we investigated how FEN1 inhibitors might impact NB cell proliferation and enhance the therapeutic efficacy of cisplatin treatment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;FEN1 was found to be highly expressed in stage IV NB and showed a strong association with cisplatin sensitivity, establishing it as a critical molecular marker linked to poor patient prognosis. Notably, elevated FEN1 expression correlated with reduced sensitivity to cisplatin, as evidenced by higher IC50 values. In the SH-SY5Y cell line, FEN1 knockdown led to significant reductions in cell proliferation, invasion, and migration, along with an increase in β-galactosidase staining-indicative of senescence. This knockdown also resulted in elevated levels of the p21 protein and decreased expression of PCNA, concurrently lowering cisplatin IC50 values. Conversely, FEN1 overexpression in the SK-N-SH cell line resulted in enhanced cell proliferation, invasion, and migration. This overexpression was associated with reduced β-galactosidase staining, decreased levels of p21, and increased expression of PCNA, ultimately resulting in higher cisplatin IC50 values. Importantly, FEN1 inhibitors alone significantly impeded NB cell proliferation, and their","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 7","pages":"1695-1708"},"PeriodicalIF":2.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction: Inhibition of Proliferation, Migration, and Invasion by Knockdown of Pyruvate Kinase-M2 (PKM2) in Ovarian Cancer SKOV3 and OVCAR3 Cells.","authors":"","doi":"10.32604/or.2025.068988","DOIUrl":"https://doi.org/10.32604/or.2025.068988","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.3727/096504016X14685034103671.].</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 7","pages":"1801-1802"},"PeriodicalIF":2.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasticity of myeloid-derived suppressor cells in cancer and cancer therapy.","authors":"Jiajia Lv, Xiaoyou Zhong, Lin Wang, Weifei Fan","doi":"10.32604/or.2025.060063","DOIUrl":"10.32604/or.2025.060063","url":null,"abstract":"<p><p>The tumor microenvironment (TME) is a complex and dynamic network comprised of tumor cells, surrounding cellular components, various signaling molecules, and the stroma. Myeloid-derived suppressor cells (MDSCs) are pivotal players in the immunosuppressive landscape of the TME, effectively hindering antitumor immune responses and facilitating tumor progression. Originating from pathologically activated myeloid precursors and relatively immature myeloid cells, MDSCs retain plasticity to further differentiate into other myeloid cells, such as macrophages or dendritic cells, which underpins their heterogeneity and adaptability in response to the TME. In this review, we delve into the plasticity of MDSCs in the tumor microenvironment and illuminate the underlying mechanisms that enable them to modulate immune responses. Furthermore, we explore the implications of MDSCs plasticity for cancer therapy, particularly its role in enhancing the efficiency of combination treatments.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 7","pages":"1581-1592"},"PeriodicalIF":2.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research review of the mechanism and clinical application prospects of tertiary lymphoid structures in the immune micro-environment of gastrointestinal tumors.","authors":"Jiang Zhu","doi":"10.32604/or.2025.058957","DOIUrl":"10.32604/or.2025.058957","url":null,"abstract":"<p><p>Changes in the intestinal immune micro-environment of the gastrointestinal tract are indispensable in the occurrence and development of gastrointestinal cancer. Tertiary lymphoid structure (TLS) is an immune cell aggregation structure found around gastrointestinal cancer in recent years. More and more research proves that tertiary lymphoid structure plays a key biological role and clinical value in disease progression, patient prognosis, and adjuvant treatment. This review aims to explore the research progress, biological significance, and potential clinical applications of TLSs in gastrointestinal tumors. The formation, development, and interaction of TLSs with tumor microenvironment have been reviewed and analyzed in recent years. Meanwhile, this review not only evaluates the clinical value of TLSs as prognostic biomarkers and predictors of treatment response but also explores their role in guiding the formulation of immunotherapy strategies for gastrointestinal tumors. In addition, this review points out the main problems in the current research of TLSs and looks forward to their future development, especially their broad application prospects in the diagnosis, treatment, and prognostic evaluation of gastrointestinal tumors.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 7","pages":"1571-1580"},"PeriodicalIF":2.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking the potential of tumor-targeting peptides in precision oncology.","authors":"Hafiz Muhammad Rehman, Sidra Ahmad, Azeem Sarwar, Hamid Bashir","doi":"10.32604/or.2025.062197","DOIUrl":"10.32604/or.2025.062197","url":null,"abstract":"<p><p>Targeted cancer therapy has emerged as a promising alternative to conventional chemotherapy, which is often plagued by poor selectivity, off-target effects, and drug resistance. Among the various targeting agents in development, peptides stand out for their unique advantages, including minimal immunogenicity, high tissue penetration, and ease of modification. Their small size, specificity, and flexibility allow them to target cancer cells while minimizing damage to healthy tissue selectively. Peptide-based therapies have shown great potential in enhancing the efficacy of drug delivery, improving tumor imaging, and reducing adverse effects. With cancer responsible for millions of deaths worldwide, the development of peptide-based therapeutics offers new hope in addressing the limitations of current treatments. As detailed studies on different aspects of targeting peptides are crucial for optimizing drug development, this review provides a comprehensive overview of the literature on tumor-targeting peptides, including their structure, sources, modes of action, and their application in cancer therapy-both as standalone agents and in fusion drugs. Additionally, various computational tools for peptide-based tumor-targeting drug design and validation are explored. The promising results from these studies highlight peptides as ideal candidates for targeted cancer therapies, offering valuable insights for researchers and accelerating the discovery of novel anti-tumor peptide base drug candidates.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 7","pages":"1547-1570"},"PeriodicalIF":2.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ETV1 transcriptional manipulation of KIFC1 regulates the progression of pancreatic cancer.","authors":"Fangfang Hu, Zhibin Bai, Yang Wang, Haodong Tang, Jiahua Zhou","doi":"10.32604/or.2025.059631","DOIUrl":"10.32604/or.2025.059631","url":null,"abstract":"<p><strong>Background: </strong>Kinesin-14 family protein 1 (KIFC1) is abnormally overexpressed in various cancers, and the transcription factor ETS variant 1 (ETV1) is an oncogenic transcription factor in tumors. The potential binding sites on the KIFC1 promoter by ETV1 were observed; however, no evidence supports that ETV1 targets KIFC1. Aims: This study aimed to investigate the relationship between KIFC1 and ETV1, and their effects and mechanisms in pancreatic cancer.</p><p><strong>Methods: </strong>Pan-cancer analysis of KIFC1 expression was performed in GEPIA2 database. KIFC1 expression levels were determined by immunohistochemistry (IHC) in our pancreatic cancer cohort. The correlation between KIFC1 expression and prognosis, tumor mutation burden, tumor purity, mismatch repair, and high-frequency tumor mutated genes was analyzed using a series of bioinformatic tools. ETV1 targeting of KIFC1 promoter transcription was determined using luciferase reporter assay. KIFC1 knockdown and ETV1 overexpression were used to determine the role of the ETV1/KIFC1 axis in cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells <i>in vitro</i> and tumor growth <i>in vivo</i>.</p><p><strong>Result: </strong>KIFC1 expression was increased in clinical specimens and pancreatic cancer cell lines and positively correlated with tumor mutation burden, tumor purity, mismatch repair, and KRAS and TP53 mutations. High KIFC1 expression was significantly associated with poor prognosis. Knockdown of KIFC1 suppressed the proliferation, migration, and invasion of pancreatic cancer cells and tumor growth. ETV1 overexpression increased KIFC1 expression and affected KIFC1 transcription. ETV1 overexpression reversed the role of KIFC1 knockdown in inhibiting cell proliferation, invasion, migration, and EMT, as validated <i>in vivo</i>.</p><p><strong>Conclusions: </strong>KIFC1 serves as a tumor activator in pancreatic cancer by promoting proliferation, migration, invasion, and tumor growth, which may be partly manipulated by ETV1.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 7","pages":"1723-1737"},"PeriodicalIF":2.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL1A: a novel prognostic biomarker and potential therapeutic target for renal clear cell carcinoma.","authors":"J I Zeng, Xueteng Meng, Yuan Zhang, Jun Li, Taotao Ma, Cheng Huang","doi":"10.32604/or.2025.061978","DOIUrl":"10.32604/or.2025.061978","url":null,"abstract":"<p><strong>Background: </strong>Renal cell carcinoma (RCC) is a prevalent malignancy characterized by a rising incidence and significant mortality. Interleukins (ILs) are crucial in regulating immune cell trafficking and exhibit anti-tumor properties. However, limited research has explored the expression levels and prognostic significance of interleukins in RCC.</p><p><strong>Methods: </strong>In this comprehensive study, we performed a detailed analysis of interleukins in RCC patients using multiple bioinformatics tools, including Oncomine, UALCAN, GEPIA, Kaplan-Meier plotter, cBioPortal, GeneMANIA, TRRUST, STRING, and Linked Omics.</p><p><strong>Results: </strong>Our analysis demonstrated a significant upregulation in the transcriptional levels of IL4, IL7, IL15, IL16, IL23A, IL26, and IL32 were significantly upregulated in RCC tissues, indicating their potential involvement in the pathogenesis of this malignancy. In contrast, IL1A, IL11, and IL27 were downregulated, indicating their potential function as tumor suppressors. Significant correlations were identified between the expression levels of IL11, IL23A, IL27, IL32, and the pathological stage of RCC patients. The expression levels of IL1A, IL4, IL11, IL15, IL16, IL23A, IL26, IL27, and IL32 were significantly correlated with improved prognosis. The differentially expressed interleukins primarily function in cytokine-cytokine receptor interactions and immune response-regulating signaling pathways. homeobox A10 (HOXA10), v-myb myeloblastosis viral oncogene homolog (avian) (MYB), v-rel reticuloendotheliosis viral oncogene homolog A (avian) (RELA), and nuclear factor of kappa light polypeptide gene enhancer in B-cells 1(NFKB1) are key transcription factors for ILs, while LCK proto-oncogene (LCK), LYN proto-oncogene (LYN), spleen associated tyrosine kinase (SYK), Janus kinase 3 (JAK3), and FER tyrosine kinase (FER) are IL targets. IL expression significantly correlated with the infiltration of six distinct immune cell types. IL1A potentially exerts an anti-tumor effect in RCC prognosis by inducing neutrophil extracellular traps (NETs). Additionally, NFKB1 may positively regulate IL1A, providing a rationale for further <i>in vivo</i> and clinical studies.</p><p><strong>Conclusion: </strong>In conclusion, our study demonstrates the potential role of IL 1A in the prognosis of RCC and establishes a theoretical foundation for subsequent <i>in vivo</i> and clinical investigations.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 7","pages":"1739-1755"},"PeriodicalIF":2.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing a prognostic signature and characterizing the tumor microenvironment based on centrosome-related genes in lung adenocarcinoma.","authors":"Lingjie Xu, Yiqin Xia, Qin Qin, Guiqun Wang, Kai Tao, Wei Wei","doi":"10.32604/or.2025.056176","DOIUrl":"10.32604/or.2025.056176","url":null,"abstract":"<p><strong>Background: </strong>The centrosome, a crucial cellular structure involved in the mitotic process of eukaryotic cells, plays a significant role in tumor progression by regulating the growth and differentiation of neoplastic cells. This makes the centrosome a promising target for therapeutic strategies in cancer treatment.</p><p><strong>Methods: </strong>Utilizing data from the TCGA database, we identified centrosome-related genes and constructed a prognostic model for 518 lung adenocarcinoma patients. Prognosis-associated genes were initially screened using univariate Cox regression, with overfitting minimized by applying LASSO regression to remove collinearity. Finally, a set of 12 genes was selected through multivariable Cox regression for inclusion in the prognostic model.</p><p><strong>Results: </strong>The model's performance was assessed using ROC curve analysis, demonstrating a robust predictive ability with an AUC of 0.728 in the training group and 0.695 in the validation group. Differential expression analysis between high-risk (HRLAs) and low-risk (LRLAs) individuals was performed, followed by enrichment analyses using KEGG, GO, Progeny, GSVA, and GSEA. These analyses revealed significant differences in immune-related pathways between the two groups. Immune microenvironment assessment through ssGSEA and ESTIMATE indicated that individuals with poor prognosis exhibited lower immune, stromal, and ESTIMATE scores, along with higher tumor purity, suggesting an impaired immune microenvironment in HRLAs patients. Drug susceptibility analysis and molecular docking showed that HRLAs individuals were more responsive to docetaxel, emphasizing the therapeutic relevance of paclitaxel in this cohort.</p><p><strong>Conclusion: </strong>We successfully developed and validated a centrosome-associated gene-based prognostic model, offering clinicians valuable insights for improved decision-making and personalized treatment strategies. This model may facilitate the identification of high-risk patients and guide therapeutic interventions in lung adenocarcinoma.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 7","pages":"1649-1666"},"PeriodicalIF":2.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-expressing PD-L1 regulates NT5E expression through MAPK/ERK pathway in triple-negative breast cancer.","authors":"Cheng Cheng, Chao Shi, Shang Wu, Weixing Wu, Jingping Li, Sinuo Gao, Meng Han, Yimin Wang, Xiangmei Zhang, Yunjiang Liu","doi":"10.32604/or.2025.061637","DOIUrl":"10.32604/or.2025.061637","url":null,"abstract":"<p><strong>Objectives: </strong>While programmed cell death 1 (PD-1) inhibitors have improved cancer treatment, the function and mechanisms of programmed cell death ligand 1 (PD-L1), particularly when expressed by cancer cells, remain unclear. This study aims to explore the role of PD-L1 within breast cancer cells and identify key targets for future immunotherapy.</p><p><strong>Methods: </strong>RNA-seq was performed on breast cancer cells with silenced PD-L1 to screen for differentially expressed genes, followed by bioinformatics analysis. Clinical specimens from breast cancer patients undergoing primary surgery without preoperative treatment were collected, along with <i>in vitro</i> analysis to validate the potential mechanism.</p><p><strong>Results: </strong>RNA-seq data revealed a significant positive correlation between Ecto-5'-nucleotidase (NT5E) expression and PD-L1. Bioinformatics analysis corroborated this positive correlation. Immunohistochemistry staining demonstrated higher NT5E expression associated with increased lymph node metastasis. High expression of the NT5E gene was associated with poor overall survival (OS) in breast cancer patients, as determined by KM plotter analysis. Following PD-L1 gene silencing by siRNA in breast cancer cells, NT5E mRNA and protein expression significantly decreased. Conversely, no significant changes were observed in PD-L1 expression after NT5E gene silencing. <i>In vitro</i> experiments confirmed that cancer cell proliferation and metastasis abilities were significantly reduced by either PD-L1 or NT5E gene down-regulation. Western blotting demonstrated that PD-L1 expressed by cancer cells regulates NT5E expression through the MAPK/ERK signaling pathway.</p><p><strong>Conclusion: </strong>This study proposes a potential mechanism wherein tumor-expressing PD-L1 regulates NT5E through the MAPK/ERK pathway. Down-regulation of PD-L1 or NT5E can significantly inhibit the proliferation and metastatic ability of cancer cells, potentially providing practical therapeutic targets and prognostic markers for combined PD-L1 immunotherapy in breast cancer.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 7","pages":"1633-1648"},"PeriodicalIF":2.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}