Translational Oncology最新文献

{"title":"BUB1B promotes cisplatin resistance in gastric cancer via Rad51-mediated DNA damage repair","authors":"Zhe Qin ,&nbsp;Fangzhou Ye ,&nbsp;Jiayi Wang,&nbsp;Jun Jiang,&nbsp;Xiaohong Zhang,&nbsp;Huanqing Li,&nbsp;Li Feng","doi":"10.1016/j.tranon.2025.102334","DOIUrl":"10.1016/j.tranon.2025.102334","url":null,"abstract":"<div><h3>Background</h3><div>Cisplatin resistance significantly impedes the treatment of gastric cancer (GC). This work examined the possible therapeutic target status and function of <em>BUB1B</em> in controlling cisplatin resistance.</div></div><div><h3>Methods</h3><div>Following the identification of differentially expressed genes (DEGs), protein-protein interaction (PPI) network analysis was conducted using datasets from the Cancer Genome Atlas-stomach adenocarcinoma (TCGA-STAD), GSE51575, and GSE79973. Functional tests assessed the effect of <em>BUB1B</em> overexpression and knockdown on the GC cells. Enrichment analysis and RNA-seq identified pathways linked to <em>BUB1B</em>. Additionally, the function of <em>BUB1B</em> in GC cells resistant to cisplatin in regulating DNA repair was examined, as its relationship with Rad51 inhibitor (B02) in regulating cell cycle, proliferation, and apoptosis. The combined effects of <em>Rad51</em> suppression and <em>BUB1B</em> overexpression on tumor development in cisplatin-resistant GC cells were further validated <em>in vivo</em> xenograft models.</div></div><div><h3>Results</h3><div>Significant overexpression of six critical overlapping genes was seen in GC tissues. The GC cell invasion, migration, and proliferation processes were improved by <em>BUB1B</em> overexpression, whereas <em>BUB1B</em> knockdown prevented these outcomes. Genes involved in DNA repair were downregulated by <em>BUB1B</em> knockdown, according to an RNA-seq study. <em>BUB1B</em> overexpression boosted cell survival via modulating cell cycle proteins, but <em>BUB1B</em> knockdown hampered DNA repair and increased death in cisplatin-resistant GC cells. Overexpression of <em>BUB1B</em> enhanced tumor development <em>in vivo</em> and counteracted the inhibitory effects of B02 on cell growth.</div></div><div><h3>Conclusion</h3><div><em>BUB1B</em> enhances cisplatin resistance in gastric cancer by regulating DNA repair and cell cycle progression, suggesting that targeting <em>BUB1B</em> may be a feasible therapeutic strategy.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102334"},"PeriodicalIF":5.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563660","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}

{"title":"Inflammasomes in lymphocytes as therapeutic targets","authors":"Zarema Albakova","doi":"10.1016/j.tranon.2025.102342","DOIUrl":"10.1016/j.tranon.2025.102342","url":null,"abstract":"<div><div>Inflammasomes are cytoplasmic macromolecular complexes playing an important role in sensing exogenous and endogenous stimuli. Inflammasome activation leads to IL-1β and IL-18 secretion and pyroptosis. The concept of non-self recognition triggering inflammasome activation has been well-established for myeloid cells. However, increasing evidence suggests the presence of functional inflammasome or inflammasome-related components in lymphocytes. Dysregulated expression of inflammasome contributes to the development of many diseases, including cardiovascular, infectious, neurodegenerative diseases and cancer. Multiple clinical trials are being conducted to assess drugs targeting various inflammasome components. This review discusses current knowledge on inflammasome activation in T, B and NK cells and explores their potential as therapeutic targets. Further understanding inflammasome and pyroptotic pathways in lymphocytes may have implications in the development of novel immunotherapeutic strategies.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102342"},"PeriodicalIF":5.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548887","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}

{"title":"Targeting FEN1/EXO1 to enhance efficacy of PARP inhibition in triple-negative breast cancer","authors":"Mallory I. Frederick ,&nbsp;Elicia Fyle ,&nbsp;Anna Clouvel ,&nbsp;Djihane Abdesselam ,&nbsp;Saima Hassan","doi":"10.1016/j.tranon.2025.102337","DOIUrl":"10.1016/j.tranon.2025.102337","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. The only targeted therapeutic approach that has emerged for early TNBC patients with BRCA-mutations (BRCA^MUT) are PARP inhibitors (PARPi). In combination, PARPi may benefit a larger cohort of TNBC patients. We used our previously identified 63-gene signature that was associated with PARPi response to identify candidate genes that could be therapeutic targets. We selected FEN1 for further investigation since its knockdown was associated with an increase in G2/M arrest, DNA damage, and apoptosis. We first tested LNT1, a FEN1/EXO1 inhibitor, in a panel of 10 TNBC cell lines. LNT1 sensitivity was identified predominantly in <em>BRCA1</em>-mutant/deficient cell lines. However, the combination of PARPi and LNT1 demonstrated a synergistic or additive effect in 7/10 cell lines, mainly in <em>BRCA1/2</em> wild-type (BRCA^WT) and <em>BRCA2</em>-mutant cell lines, with intrinsic and acquired resistance to PARPi. The greatest synergy was observed in a <em>BRCA2</em>-mutant cell line with acquired resistance to olaparib (HCC1395-OlaR), with a combination index value of 0.20. In the synergistic cell lines, BT549 (BRCA^WT) and HCC1395-OlaR, the combination was associated with a rapid progression in DNA replication fork speed, an early and sustained increase in DNA damage in comparison to each of the single-agents. However, in the additive BRCA1/2 wild-type cell lines, MDAMB231 and HCC1806, the combination demonstrated a high DNA damage response that was largely driven by either talazoparib or LNT1. Therefore, targeting FEN1/EXO1 with PARPi is a promising targeted combination approach, particularly in the context of PARPi-resistant and BRCA^WT TNBC.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102337"},"PeriodicalIF":5.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548886","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}

{"title":"TTC7A-ALK, a novel ALK fusion variant identified in a patient with metastatic lung adenocarcinoma, exhibits excellent response to crizotinib","authors":"Meijin Huang ,&nbsp;Xiangqing Zhu ,&nbsp;Wenmang Xu ,&nbsp;Jun Zhu ,&nbsp;Xin Xun ,&nbsp;Bin Su ,&nbsp;Hong Chen","doi":"10.1016/j.tranon.2025.102345","DOIUrl":"10.1016/j.tranon.2025.102345","url":null,"abstract":"<div><div>Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. <em>ALK</em> gene rearrangement has been identified in 3 % to 5 % of the patients with NSCLC. Thanks to the advancements in second-generation sequencing technology, an increasing number of novel fusion partners have been identified. In our research, we discovered a rare <em>ALK</em> fusion, <em>TTC7A-ALK</em>, in a patient with advanced lung adenocarcinoma using targeted next-generation sequencing (NGS). After being diagnosed with advanced lung adenocarcinoma with <em>TTC7A-ALK</em> fusion<em>,</em> the patient received crizotinib treatment and achieved a progression-free survival of 29 months. Additonanlly, we conducted further functional analyses on this fusion protein to assess its oncogenic potential. Similar to <em>EML4-ALK</em>, the <em>TTC7A-ALK</em> fusion protein can promote the growth of Ba/F3 cells under IL-3-independent conditions in vitro. In vivo studies demonstrate that the <em>TTC7A-ALK</em> fusion protein could enhance the tumorigenesis of NIH3T3 cells in nude mice, which can be suppressed by crizotinib. Mechanistic studies indicated that the ectopic expression of <em>TTC7A-ALK</em> in 293T cells led to the hyperactivation of downstream MAPK and PI3K/Akt pathways, which can be inhibited by crizotinib. Furthermore, upon tumor progression, the patient transitioned to alectinib, which provided rapid symptom relief and controlled the majority of lesions. Conclusionly, we identified and validated <em>TTC7A-ALK</em> as a oncogenic fusion in NSCLC. The patient demonstrated a significant clinical benefit from sequential treatment with crizotinib and alectinib, highlighting <em>TTC7A-ALK</em> as a novel therapeutic target for <em>ALK</em> inhibitors. These findings extend the spectrum of actionable <em>ALK</em> fusions and promote the inclusion of rare fusion detection in clinical diagnostic processes and treatment strategies.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102345"},"PeriodicalIF":5.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563588","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}

{"title":"Evaluation of a novel ensemble model for preoperative ovarian cancer diagnosis: Clinical factors, O-RADS, and deep learning radiomics","authors":"Yimin Wu ,&nbsp;Lifang Fan ,&nbsp;Haixin Shao ,&nbsp;Jiale Li ,&nbsp;Weiwei Yin ,&nbsp;Jing Yin ,&nbsp;Weiyu Zhu ,&nbsp;Pingyang Zhang ,&nbsp;Chaoxue Zhang ,&nbsp;Junli Wang","doi":"10.1016/j.tranon.2025.102335","DOIUrl":"10.1016/j.tranon.2025.102335","url":null,"abstract":"<div><h3>Background</h3><div>Accurate early diagnosis of ovarian cancer is crucial. The objective of this research is to create a comprehensive model that merges clinical variables, O-RADS, and deep learning radiomics to support preoperative diagnosis and assess its efficacy for sonographers.</div></div><div><h3>Materials and methods</h3><div>Data from two centers were used: Center 1 for training and internal validation, and Center 2 for external validation. DL and radiomics features were extracted from transvaginal ultrasound images to create a DL radiomics model using the LASSO method. A machine learning model ensemble was created by merging clinical variables, O-RADS scores, and DL radiomics model predictions. The model's effectiveness was evaluated by measuring the area under the receiver operating characteristic curve (AUC) and analyzing its impact on improving the diagnostic skills of sonographers. Moreover, the model's additional usefulness was assessed through integrated discrimination improvement (IDI), net reclassification improvement (NRI), and subgroup analysis.</div></div><div><h3>Results</h3><div>The ensemble model demonstrated superior diagnostic performance for ovarian cancer compared to standalone clinical models and clinical O-RADS models. Notably, there were significant improvements in the NRI and IDI across all three datasets, with p-values &lt; 0.05. The ensemble model exhibited exceptional diagnostic performance, achieving AUCs of 0.97 in both the internal and external validation sets. Moreover, the implementation of this ensemble model substantially improved the diagnostic precision and reliability of sonographers. The sonographers' average AUC improved by 11 % in the internal validation set and by 7.7 % in the external validation set.</div></div><div><h3>Conclusions</h3><div>The ensemble model significantly enhances preoperative ovarian cancer diagnosis accuracy and improves sonographers' diagnostic capabilities and consistency.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102335"},"PeriodicalIF":5.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548901","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}

{"title":"Targeted mitochondrial therapy for pancreatic cancer","authors":"Xinya Zhao ,&nbsp;Guoyu Wu ,&nbsp;Xufeng Tao ,&nbsp;Deshi Dong ,&nbsp;Jing Liu","doi":"10.1016/j.tranon.2025.102340","DOIUrl":"10.1016/j.tranon.2025.102340","url":null,"abstract":"<div><div>Pancreatic cancer (PC) is a highly invasive tumor characterized by delayed diagnosis, rapid progress, and resistance to chemotherapy. Mitochondria, as the \"power chamber\" of cells, not only play a central role in energy metabolism but also participate in the production of reactive oxygen species (ROS), calcium signaling, regulation, and differentiation of the cell cycle. The abnormal activity of mitochondria is closely related to the development of PC. In this paper, we discussed the key role of mitochondria in PC, including mitochondrial DNA, mitochondrial biogenesis, mitochondrial dynamics, metabolic regulation, ROS generation, and mitochondrial-dependent apoptosis. We elaborated on the importance of these mitochondrial mechanisms in the development of PC and emphasized the potential of targeted mitochondrial therapy strategies for these mechanisms in the treatment of PC. In addition, this article also reviews the latest developments in innovative drug carriers such as cell-penetrating peptides, nucleic acid aptamers, and nanomaterials, which can achieve precise localization of mitochondria and drug delivery. Therefore, this article comprehensively analyzed the important role of mitochondria in the treatment of PC and clarified the effectiveness and necessity of targeting mitochondria in the treatment of PC.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102340"},"PeriodicalIF":5.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548899","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}

{"title":"Synergistic effects of HO-1 inhibition and chemotherapy on tumor proliferation and immune infiltration: An in vitro and in vivo approach to enhancing prostate cancer treatment","authors":"Ramia J. Salloom ,&nbsp;Dania Z. Sahtout ,&nbsp;Iman M. Ahmad ,&nbsp;Maher Y. Abdalla","doi":"10.1016/j.tranon.2025.102339","DOIUrl":"10.1016/j.tranon.2025.102339","url":null,"abstract":"<div><div>Prostate cancer (PC) remains a leading cause of morbidity and mortality among men worldwide, highlighting the need for novel therapeutic strategies. Our study investigates the therapeutic potential of targeting the heme degradation pathway through heme oxygenase-1 (HO-1) inhibition in PC. Using both <em>in vitro</em> and <em>in vivo</em> models, we explored the effects of combining HO-1 inhibition with chemotherapy, represented by docetaxel (Doc), on tumor growth and immune infiltration. <em>In vitro</em> experiments demonstrated that HO-1 inhibition, as well as HO-1 knockout (KO), significantly reduced tumor cell proliferation and enhanced chemosensitivity in RM-1 cells. Additionally, U937 cells co-cultured with HO-1 KO cells shifted cell polarization toward an M1 phenotype. <em>In vivo</em>, the combined treatment of the HO-1 inhibitor, tin protoporphyrin (SnPP), with Doc significantly enhanced anti-tumor efficacy in mouse models compared to chemotherapy or SnPP alone. This combination therapy not only reduced Ki67 expression and increased CC3 expression in tumor tissues but also shifted macrophage polarization toward an M1 phenotype and enhanced CD4⁺ and CD8⁺ T cells infiltration, indicating an augmented immune response. Further investigation using macrophage-specific HO-1 knockout mice revealed a direct role of HO-1 inhibition in driving macrophage polarization, confirming its involvement in promoting the shift toward an M1 phenotype. Although this response was significant, it was more robust with systemic HO-1 inhibition. Our findings indicate that HO-1 inhibition can potentiate the effects of chemotherapy, offering a promising avenue for improving PC treatment outcomes.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102339"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548900","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}

{"title":"Corrigendum to “PMAIP1-Mediated Glucose Metabolism and its Impact on the Tumor Microenvironment in Breast Cancer: Integration of Multi-Omics Analysis and Experimental Validation” [Translational Oncology 52C (2024) 102267]","authors":"Yidong Zhang ,&nbsp;Hang Xu ,&nbsp;Xuedan Han ,&nbsp;Qiyi Yu ,&nbsp;Hua Xiao ,&nbsp;Lufeng Zheng","doi":"10.1016/j.tranon.2025.102285","DOIUrl":"10.1016/j.tranon.2025.102285","url":null,"abstract":"","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"53 ","pages":"Article 102285"},"PeriodicalIF":5.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510791","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}

{"title":"SPRY1 regulates macrophage M1 polarization in skin aging and melanoma prognosis","authors":"Rongxin Zhao ,&nbsp;Xun Zhang ,&nbsp;Yingnan Geng ,&nbsp;Dan Lu ,&nbsp;Yuqing Wang ,&nbsp;Han Xie ,&nbsp;Xiaofei Zhang ,&nbsp;Shunming Xu ,&nbsp;Yanyun Cao","doi":"10.1016/j.tranon.2025.102331","DOIUrl":"10.1016/j.tranon.2025.102331","url":null,"abstract":"<div><h3>Introduction</h3><div>Skin aging is a complex, multifactorial process involving cellular damage, inflammation, and increased susceptibility to diseases. Despite its importance, the role of SPRY1 in skin aging remains poorly understood. This study aims to investigate the function of SPRY1 in skin aging, particularly its impact on macrophage M1 polarization, and explore its potential as a therapeutic target for mitigating skin aging and melanoma.</div></div><div><h3>Methods</h3><div>Bioinformatics analyses were performed using datasets from the GTEx and GEO databases, alongside in vitro cellular experiments. These included Weighted Gene Co-expression Network Analysis (WGCNA), single-cell sequencing, and various cellular assays in RAW264.7 murine monocyte/macrophage leukemia cells and NIH/3T3 mouse skin fibroblasts. The assays comprised gene transfection, Cell Counting Kit-8 (CCK-8) assays, quantitative real-time PCR (qRT-PCR), and measurements of reactive oxygen species (ROS) and superoxide dismutase (SOD) activity.</div></div><div><h3>Results</h3><div>SPRY1 was identified as a key gene within modules linked to skin aging. Single-cell sequencing revealed its enrichment in macrophages and keratinocytes. Knockdown of SPRY1 in RAW264.7 cells resulted in a shift from M1 to M2 macrophage polarization, reduced oxidative stress, and decreased expression of inflammatory markers. In NIH/3T3 cells, SPRY1 knockdown reduced cell viability and lowered the expression of inflammatory genes. Additionally, SPRY1 expression was downregulated in melanoma, and its reduced levels were associated with poorer survival outcomes.</div></div><div><h3>Conclusions</h3><div>SPRY1 accelerates skin aging by promoting macrophage M1 polarization and may serve as a promising therapeutic target. Future research should focus on in vivo validation and further exploration of its regulatory networks to develop novel treatments.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102331"},"PeriodicalIF":5.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520377","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}

{"title":"Discovering the Potential Role of the C2 DUSP2+ MCs Subgroup in Lung Adenocarcinoma","authors":"Shengyi Zhang ,&nbsp;Xinhan Li ,&nbsp;Zhikai Xiahou ,&nbsp;Ailing Chen ,&nbsp;Renfang Sun ,&nbsp;Chao Liu ,&nbsp;Jie Yuan","doi":"10.1016/j.tranon.2025.102295","DOIUrl":"10.1016/j.tranon.2025.102295","url":null,"abstract":"<div><h3>Objective</h3><div>In both industrialized and developing nations worldwide, lung adenocarcinoma is one of the deadliest malignant tumors and the primary cause of cancer-related deaths. Its cellular heterogeneity is unclear to the fullest extent, although in recent years, its prevalence in younger individuals has increased. Therefore, it is urgent to deepen the understanding of lung adenocarcinoma and explore new therapeutic methods.</div></div><div><h3>Methods</h3><div>CytoTRACE, Monocle, SCENIC, and enrichment analysis were used to analyze the single cell RNA data, we characterized the biological characteristics of mast cells (MCs) in lung adenocarcinoma patient samples. CellChat was used to analyze and validate the interaction between MCs and tumor cells in lung adenocarcinoma. Prognostic models were used to evaluate and predict the development trend and outcome of a patient's disease, such as the survival time of cancer patients. The python package SCENIC was used to evaluate the enrichment of transcription factors and the activity of regulators in lung adenocarcinoma cell subgroups. CCK-8 assay could validate the activity of a specific cell subgroup sequenced in single cell sequencing to confirm the role of this cell subgroup in tumor proliferation.</div></div><div><h3>Results</h3><div>Our analysis identified seven major cell types, further grouping MCs within them and identifying four distinct subgroups, including MCs with high <em>DUSP2</em> expression, which showed some tumor-related characteristics. In addition, we identified the key signaling receptor <em>EGFR</em> and validated it through in vitro knockdown experiments, demonstrating its role in promoting cancer. In addition, we established an independent prognostic indicator, the <em>DUSP2</em>+ MCs risk score, which showed an association between groups with high risk scores and poor outcomes.</div></div><div><h3>Conclusion</h3><div>These findings shed light on the complex interactions in the lung adenocarcinoma tumor microenvironment and suggest that targeting specific MCs subgroups, particularly through the <em>EGFR</em> signaling pathway, may provide new therapeutic strategies.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102295"},"PeriodicalIF":5.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508252","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}