Translational Oncology最新文献

{"title":"APOA1 promotes tumor proliferation and migration and may be a potential pan-cancer biomarker and immunotherapy target","authors":"Peiyi Xu ,&nbsp;Qiuyan Zhang ,&nbsp;Jing Zhai,&nbsp;Pu Chen,&nbsp;Xueting Deng,&nbsp;Lin Miao,&nbsp;Xiuhua Zhang","doi":"10.1016/j.tranon.2025.102344","DOIUrl":"10.1016/j.tranon.2025.102344","url":null,"abstract":"<div><h3>Introduction</h3><div>Aberrant expression of APOA1 has been reported in various cancers. However, a comprehensive investigation into its role in cancer is currently lacking.</div></div><div><h3>Methods</h3><div>Online websites and databases such as TIMER2.0, GEPIA2, UALCAN and GSCA were used to investigate the relationship between APOA1 expression and prognostic value, immune infiltration, gene mutations, and drug sensitivity. In addition, in vitro CCK-8 and transwell migration and invasion assays were performed to determine the biological functions of APOA1 in gastric cancer (GC) cells.</div></div><div><h3>Results</h3><div>The pan-cancer analysis showed that APOA1 is differentially expressed in different cancer types and significantly correlated with tumor stages. A survival analysis revealed that APOA1 predicted a poor prognosis in ACC, KIRC, STAD, and a good prognosis in BRCA, OV, and UCEC. We also found that the most common genetic alteration type of APOA1 was deep deletion, and the DNA methylation level of APOA1 decreased in various cancers. Furthermore, APOA1 expression negatively correlated with immune cells infiltration in cancers, including CD4+ T, CD8+ T, and myeloid dendritic cells. For STAD, GO/KEGG enrichment analysis revealed the possible involvement of APOA1 in cholesterol metabolism and PPAR signaling pathway. Finally, we further performed in vitro experiments to verify that overexpression of APOA1 could promote the proliferation, migration and invasion of GC cells.</div></div><div><h3>Conclusion</h3><div>The results of this study indicate that APOA1 is a potential tumor prognostic biomarker and immunotherapy target. In addition, APOA1 plays an essential role in the proliferation, migration, and invasion of GC cells by vitro experiments.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"55 ","pages":"Article 102344"},"PeriodicalIF":5.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620073","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":"Leveraging machine learning for integrative analysis of T-cell receptor repertoires in colorectal cancer: Insights into MAIT cell dynamics and risk assessment","authors":"Romi Goldner Kabeli ,&nbsp;Ben Boursi ,&nbsp;Alona Zilberberg ,&nbsp;Sol Efroni","doi":"10.1016/j.tranon.2025.102358","DOIUrl":"10.1016/j.tranon.2025.102358","url":null,"abstract":"<div><div>This study investigates the T-cell receptor (TCR) repertoires in colorectal cancer (CRC) patients by analyzing three distinct datasets: one bulk sequencing dataset of 205 patients with various tumor stages, all newly diagnosed at Sheba Medical Center between 2017 and 2022, with minimal recruitment in 2014 and 2016, and two (public) single-cell sequencing datasets of 10 and 12 patients. Despite the significant variability in the TCR repertoire and the low likelihood of sequence overlap, our analysis reveals an interesting set of TCR sequences across these data. Notably, we observe elevated presence of mucosal-associated invariant T (MAIT) cells in both metastatic and non-metastatic patients. Furthermore, we identify nine identical TCR alpha and TCR beta pairs that appear in both single-cell datasets, with 13 out of 18 sequences from these sequences also appearing in the bulk data. Clinical risk analysis over the bulk dataset, using a subset of these unique sequences, demonstrates a correlation between TCR repertoire disease stage and risk. These findings enhance our understanding of the TCR landscape in CRC and underscore the potential of TCR sequences as biomarkers for disease outcome.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"55 ","pages":"Article 102358"},"PeriodicalIF":5.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620066","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":"Exploring the link between low germline mutational load and low breast cancer incidence: Lessons from the Xavante Indians","authors":"José Rueff ,&nbsp;João Conde ,&nbsp;Guilherme Castro","doi":"10.1016/j.tranon.2025.102356","DOIUrl":"10.1016/j.tranon.2025.102356","url":null,"abstract":"<div><div>The study of cancer, its initiation, and its mechanisms of progression has been a focal point in science for more than a century. Despite controversies among scientists, there is a growing consensus to determine the moment when a cell gains the capacity to be transformed and whether this mechanism is to be attributed to germinal or somatic events, or possibly both. The case of the Xavante Indians is a beacon for this journey, pointing toward the importance of genetic diversity in shaping our approach to cancer research and treatment. As we incorporated these lessons into clinical practice, we embarked on a new era of personalized preventative healthcare strategies against cancer. Based on recent data, we comment on the low germinal mutational load and low cancer incidence. Statistical analyses reveal a significantly lower mutation burden in Xavante women compared to global populations (<em>p</em> &lt; 0.0001), including rare deleterious variants in cancer-associated genes. Additionally, polygenic risk scores (PRS) for breast cancer are markedly lower in Xavante (mean PRS ∼35) compared to TCGA cohorts (∼80–90) (<em>p</em> &lt; 0.0001). The absence of breast cancer cases in Xavante is statistically significant when compared to expected rates (<em>p</em> &lt; 0.001), reinforcing the hypothesis of a protective genetic landscape.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"55 ","pages":"Article 102356"},"PeriodicalIF":5.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143611009","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":"Single cell analysis reveals that SPP1+ macrophages enhance tumor progression by triggering fibroblast extracellular vesicles","authors":"Haocheng Wang ,&nbsp;Bowen Qiu ,&nbsp;Xinyu Li ,&nbsp;Yao Ying ,&nbsp;Yue Wang ,&nbsp;Hungchen Chen ,&nbsp;Fanan Zeng ,&nbsp;Junyao Shi ,&nbsp;Junpeng Huang ,&nbsp;Ziying Wu ,&nbsp;Zequn Chen ,&nbsp;Xiao Che ,&nbsp;Qingzhong Li ,&nbsp;Yingming Fan ,&nbsp;Bingyao Li ,&nbsp;Qun Wang ,&nbsp;Chengyu Huang ,&nbsp;Yixuan Chen ,&nbsp;Ting Li ,&nbsp;Ke Mo ,&nbsp;Chunhui Cui","doi":"10.1016/j.tranon.2025.102347","DOIUrl":"10.1016/j.tranon.2025.102347","url":null,"abstract":"<div><div>Patients with liver metastatic colorectal cancer (mCRC) have a poor prognosis and are the leading cause of death in colorectal cancer (CRC) patients, but the mechanisms associated with CRC metastasis have not been fully elucidated. In this study, we obtained data from the Gene Expression Omnibus database and characterized the single-cell profiles of CRC, mCRC and healthy samples at single-cell resolution, and explored the cells that influence CRC metastasis. We find that AQP1⁺ CRC identified as highly malignant tumor cells exhibited proliferative and metastatic characteristics. Immunosuppressive properties are present in the tumor microenvironment (TME), while NOTCH3⁺ Fib is identified to play a facilitating role in the metastatic colonization of CRC. Importantly, we reveal that tumor-associated macrophages (TAM) characterized by SPP1-specific high expression may be involved in TME remodeling through intercellular communication. Specifically, SPP1⁺ TAM mediates the generation of Fib-derived extracellular vesicle through the APOE-LRP1 axis, which in turn delivers tumor growth-promoting factors in the TME. This study deepens the understanding of the mechanism of TME in mCRC and lays the scientific foundation for the development of therapeutic regimens for mCRC patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"55 ","pages":"Article 102347"},"PeriodicalIF":5.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143611032","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":"A machine learning-based prognostic signature utilizing MSC proteomics for predicting bladder cancer prognosis and treatment response","authors":"Xinyu Zhang ,&nbsp;Pan Li ,&nbsp;Luhua Ji ,&nbsp;Yuanfeng Zhang,&nbsp;Ze Zhang,&nbsp;Yufeng Guo,&nbsp;Luyang Zhang,&nbsp;Suoshi Jing,&nbsp;Zhilong Dong,&nbsp;Junqiang Tian,&nbsp;Li Yang,&nbsp;Hui Ding,&nbsp;Enguang Yang,&nbsp;Zhiping Wang","doi":"10.1016/j.tranon.2025.102349","DOIUrl":"10.1016/j.tranon.2025.102349","url":null,"abstract":"<div><h3>Background</h3><div>Mesenchymal stem cells (MSCs), due to their tumor-targeting homing properties, are present in the tumor microenvironment (TME) and influence the biological behaviors of tumors. The purpose of this paper is to establish a signature based on the MSC secretome to predict the prognosis and treatment of bladder cancer (BLCA).</div></div><div><h3>Methods</h3><div>The presence of MSCs in BLCA was validated through flow cytometry and multiplex fluorescence immunohistochemistry (mFIHC), and the relationships between MSCs and clinical characteristics were explored. Unsupervised clustering analysis was performed on BLCA according to the differential proteins detected in MSC-conditioned medium (MSC<img>CM) using a cytokine array. Using the TCGA-BLCA, GSE32548, and GSE32894 datasets as background data, a risk signature was constructed according to the differential proteins in MSC<img>CM through machine learning. For the risk groups with high and low prognoses, we calculated Kaplan-Meier (K-M) curves. Additionally, we explored the relationships between the signature and the tumor immune landscape, response to immunotherapy, and chemotherapy drugs.</div></div><div><h3>Results</h3><div>Both flow cytometry and mFIHC confirmed the presence of MSCs in bladder tumors, and clinical samples revealed correlations between MSCs and the pathological grade, T stage, and Ki67 in BLCA. Based on differential proteins and unsupervised clustering analysis, BLCA patients were divided into two groups, and significant differences were found between these groups in terms of TME, immune response, and clinical treatments. Using machine learning, a signature was constructed with the combination algorithm Stepcox (both) + plsRcox, revealing significant survival differences between the high- and low-risk MSC groups. Regression analyses, along with ROC curves, further demonstrated that risk score independently predict the prognosis of patients with high predictive performance. Moreover, there were notable differences between the high- and low-risk groups in terms of the TME scores, immune infiltration, and immune checkpoints. For BLCA immunotherapy, the low-risk group suggested better efficacy, while conventional chemotherapy drugs such as gemcitabine and cisplatin might be less effective in the low-risk group.</div></div><div><h3>Conclusion</h3><div>The signature based on MSC secreted protein profiles could effectively predict the prognosis of BLCA and provided valuable guidance for treatment and drug resistance.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102349"},"PeriodicalIF":5.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143591652","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":"Single-cell insights into HNSCC tumor heterogeneity and programmed cell death pathways","authors":"Yuanhao Chai ,&nbsp;Jianlin Zhang ,&nbsp;Wenwen Shao ,&nbsp;Ziwei Zhang","doi":"10.1016/j.tranon.2025.102341","DOIUrl":"10.1016/j.tranon.2025.102341","url":null,"abstract":"<div><h3>Background</h3><div>Head and neck squamous cell carcinoma (HNSCC) is a prevalent malignancy often diagnosed in advanced stages. Despite advancements in therapy, it retains a high mortality rate and significant recurrence risk. This study utilizes single-cell sequencing (scRNA-seq) to unravel HNSCC's complexity, identify therapeutic targets, and refine prognostic models.</div></div><div><h3>Methods</h3><div>Pseudotime trajectory and stemness analyses were performed on HNSCC tumor subpopulations, focusing on the C2 <em>MALAT1</em>+ Tumors subpopulation, which had the lowest CytoTRACE Score and represented the Lineage 2 endpoint in Slingshot analysis. The study examined programmed death and metabolic pathways in each subpopulation and developed a novel prognostic model using LASSO regression.</div></div><div><h3>Results</h3><div>The C2 <em>MALAT1</em>+ Tumors subpopulation exhibited reduced expression of programmed death pathways (e.g., Entotic cell death, Apoptosis, Pyroptosis) and metabolic pathways (e.g., Riboflavin metabolism, Glycolysis/Gluconeogenesis). Key transcription factors included LEF1, RFX3, CREM, MZF1, and ZNF202. Prognostic models based on the <em>MALAT1</em> Tumors Risk Score (MTRS) revealed worse survival and higher tumor purity in the high MTRS group. Risk genes included <em>ADM, RPL31, EIF5B</em>, and <em>TAF7</em>. Additionally, activated CD4 memory T cells were enriched in the high MTRS group, which also showed greater sensitivity to Cisplatin, Docetaxel, and Paclitaxel.</div></div><div><h3>Conclusions</h3><div>ScRNA-seq revealed the heterogeneity of HNSCC subpopulations, highlighting the unique features of the C2 <em>MALAT1</em>+ Tumors subpopulation. This study identified novel prognostic markers and therapeutic targets, offering insights into HNSCC progression, drug resistance, and potential treatments.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102341"},"PeriodicalIF":5.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579646","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":"Tumor-stroma proportion is associated with increased M2 macrophage abundance and predicts the resistance to immune checkpoint blockade in breast cancer","authors":"Yincheng Liu ,&nbsp;Ningyi Xue ,&nbsp;Yuelin Liu ,&nbsp;Jie Mei ,&nbsp;Yun Cai ,&nbsp;Zhenghui Wang ,&nbsp;Hongxin Lin ,&nbsp;Mengyun Wan ,&nbsp;Ji Zhou ,&nbsp;Tiansong Xia ,&nbsp;Yichao Zhu ,&nbsp;Shui Wang","doi":"10.1016/j.tranon.2025.102343","DOIUrl":"10.1016/j.tranon.2025.102343","url":null,"abstract":"<div><h3>Background</h3><div>The tumor stroma has been reported to be associated with worse prognosis in several solid tumors, but its prognostic value in breast cancer (BRCA) is still undefined.</div></div><div><h3>Methods</h3><div>In this research, multiple public and in-house patient cohorts were collected to demonstrate the clinical and immune correlations of tumor-stroma proportion (TSP) in BRCA. In addition, <em>in vitro</em> assays uncovered the oncogenic role of TSP-related collagen in BRCA.</div></div><div><h3>Results</h3><div>High TSP status based on hematoxylin and eosin (HE) staining was associated with positive hormone receptor status, advanced clinical stages, and poor immune checkpoint blockade (ICB) response. In addition, we developed a RNA-sequencing (RNA-seq)-based stromal score based on four critical genes expression (AEBP1, COL6A3, CTSK, and PLAC9). Both TSP status and stromal score were positively associated with increased M2 macrophage abundance in BRCA. Moreover, tumor collagen has been found to be enriched in samples with the high TSP status, and collagen promoted BRCA cells aggressiveness and macrophage M2 polarization.</div></div><div><h3>Conclusions</h3><div>The tumor stroma was found to be notably related to poor ICB response in patients with BRCA as a result of tumor stroma-macrophage interactions. Thus, the TSP status could predict the clinical outcomes of BRCA patients receiving ICB therapy.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102343"},"PeriodicalIF":5.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579647","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":"Comprehensive assessment of serum 3′-tRFArg as a novel diagnostic biomarker for gastric cancer","authors":"Rui Ding ,&nbsp;Yang Li ,&nbsp;Yu Zhang ,&nbsp;Xun Li ,&nbsp;Yunjian Song ,&nbsp;Xinliang Gu ,&nbsp;Xianjuan Shen ,&nbsp;Shaoqing Ju","doi":"10.1016/j.tranon.2025.102338","DOIUrl":"10.1016/j.tranon.2025.102338","url":null,"abstract":"<div><div>Gastric cancer is one of the malignant tumors with the highest morbidity and mortality rates worldwide. Yet, there is a lack of diagnostic markers with high sensitivity in the clinic. tRNA-derived small RNAs are a novel type of non-coding small RNAs, which are abundant in tumor cells and body fluids. In this study, we explored the potential of 3′-tRF^Arg as a tumor marker for the diagnosis of GC. Differential expression of 3′-tRF^Arg was screened by high-throughput sequencing, and Quantitative real-time PCR confirmed its low expression in GC serum with good stability. Differential expression of serum 3′-tRF^Arg could distinguish between GC patients, gastritis patients, and healthy donors and was significantly correlated with clinical pathological features such as tumor differentiation, lymph node metastasis, and TNM staging. The receiver operating characteristic curve showed that 3′-tRF^Arg had a higher diagnostic value compared with conventional biomarkers, especially in the diagnosis of early gastric cancer. In conclusion, our results suggest that 3′-tRF^Arg can serve as a highly sensitive biomarker with a certain value for monitoring tumor development and prognosis.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102338"},"PeriodicalIF":5.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143580306","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":"Immunomodulation on tumor immune microenvironment in acquired targeted therapy resistance and implication for immunotherapy resistance","authors":"Ming-Yu Chou ,&nbsp;Muh-Hwa Yang","doi":"10.1016/j.tranon.2025.102353","DOIUrl":"10.1016/j.tranon.2025.102353","url":null,"abstract":"<div><div>The emergence of molecularly targeted therapies and immunotherapies has revolutionized cancer treatment, yet the optimal sequencing of these modalities remains debated. While targeted therapies often induce initial immunostimulatory effects, the development of resistance is accompanied by dynamic alterations in the tumor-immune microenvironment. These changes can promote tumor growth, hinder immune surveillance, and contribute to subsequent immunotherapy resistance. This review focuses on solid tumors and summarizes the immunomodulatory effects arising in the context of targeted therapy resistance, highlighting the challenges they pose for the subsequent immunotherapy efficacy.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102353"},"PeriodicalIF":5.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579648","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":"The pancreatitis-cancer transformation-related factor, human rhomboid family-1, promotes pancreatic cancer progression through the SRC/YAP signaling pathway","authors":"Zhilong Ma ,&nbsp;Jie Hua ,&nbsp;Miaoyan Wei ,&nbsp;Lin Han ,&nbsp;Mingwei Dong ,&nbsp;Wangcheng Xie ,&nbsp;Tingyi Luo ,&nbsp;Qingcai Meng ,&nbsp;Wei Wang ,&nbsp;Zhenshun Song ,&nbsp;Si Shi ,&nbsp;Xianjun Yu ,&nbsp;Jin Xu","doi":"10.1016/j.tranon.2025.102346","DOIUrl":"10.1016/j.tranon.2025.102346","url":null,"abstract":"<div><div>Pancreatic cancer is an aggressive malignancy characterized by rapid progression, unfavorable outcomes, and a low early detection rate. Elucidating the mechanisms underlying the onset and progression of pancreatic tumors is essential for early detection and for developing preventive measures. Even though human rhomboid family-1 (RHBDF) acts as an oncogene in various tumors, the role of RHBDF in pancreatic cancer progression remains unexplored. Here, publicly available datasets, including samples of chronic pancreatitis associated with pancreatic cancer from our center, were used for bioinformatics analyses, including differential expression, survival, and enrichment studies. The findings were validated by immunohistochemical staining and in vitro experiments. We found that RHBDF1 was significantly upregulated in tumor samples relative to adjacent non-tumor and pancreatitis tissues, and its expression increased in correlation with the progression of pancreatitis to cancer. Furthermore, RHBDF1 promoted the proliferation, migration, and invasion of pancreatic cancer cells, and in vivo studies demonstrated that RHBDF1 promoted pancreatic cancer progression, tissue fibrosis, and the formation of new blood vessels. RNA-sequencing and cell functional experiments indicated that RHBDF1 promotes the progression of pancreatic cancer through the SRC-YAP signaling pathway. In summary, the pancreatitis-cancer transformation-related factor, RHBDF1, promotes pancreatic cancer progression by activating the SRC-YAP signaling cascade, indicating that RHBDF1 could be a viable target for the diagnosis and treatment of early-stage pancreatic cancer.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102346"},"PeriodicalIF":5.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143580305","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}