Translational Oncology最新文献

{"title":"Mechanisms of radioresistance and radiosensitization strategies for Triple Negative Breast Cancer","authors":"Yuxuan Wang ,&nbsp;Zhiwei Liu ,&nbsp;Yulu Lv ,&nbsp;Jiayang Long ,&nbsp;Yao Lu ,&nbsp;Panpan Huang","doi":"10.1016/j.tranon.2025.102351","DOIUrl":"10.1016/j.tranon.2025.102351","url":null,"abstract":"<div><div>Breast cancer is one of the most common malignant tumors in women. Triple-negative breast cancer (TNBC) is a molecular subtype of breast cancer that is characterized by a high risk of recurrence and poor prognosis. With the increasingly prominent role of radiotherapy in TNBC treatment, patient resistance to radiotherapy is an attractive area of clinical research. Gene expression changes induced by multiple mechanisms can affect the radiosensitivity of TNBC cells to radiotherapy through a variety of ways, and the enhancement of radioresistance is an important factor in the malignant progression of TNBC. The above pathways mainly include DNA damage repair, programmed cell death, cancer stem cells (CSC), antioxidant function, tumor microenvironment, and epithelial–mesenchymal transition (EMT) pathway. Tumor cells can reduce the damage of radiotherapy to themselves through the above ways, resulting in radioresistance. Therefore, in this review, we aim to summarize the strategies for immunotherapy combined with radiotherapy, targeted therapy combined with radiotherapy, and epigenetic therapy combined with radiotherapy to identify the best treatment for TNBC and improve the cure and survival rates of patients with TNBC. This review will provide important guidance and inspiration for the clinical practice of radiotherapy for TNBC, which will help deepen our understanding of this field and promote its development.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"55 ","pages":"Article 102351"},"PeriodicalIF":5.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643718","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":"Tubeimoside I induces mitophagy by activating the PINK1/Parkin/Mfn2 signaling pathway in acute myeloid leukemia cells","authors":"Jing Xu ,&nbsp;Fanggang Ren ,&nbsp;Jinjuan Wang ,&nbsp;Jianbing Liu ,&nbsp;Xiaohua Cui ,&nbsp;Jianqing Hao ,&nbsp;Wanfang Yang ,&nbsp;Yaofang Zhang ,&nbsp;Dongmin Cao ,&nbsp;Li Li ,&nbsp;Hongwei Wang","doi":"10.1016/j.tranon.2025.102355","DOIUrl":"10.1016/j.tranon.2025.102355","url":null,"abstract":"<div><div>Acute myeloid leukemia (AML) is the most prevalent kind of acute leukemia in adults. Despite the availability of new targeted therapies, AML remains connected with a poor prognosis and decreased rate of survival. Tubeimoside I (TBMS1), a critical compound extracted from <em>Bolbostemma paniculatum</em>, has demonstrated potential anticancer effects in lung and colorectal cancers. Nevertheless, the TBMS1 anticancer pathway against AML is still elusive. This study aimed to explore the potential role of TBMS1 in anti-AML and its molecular mechanism. <em>In vitro</em>, TBMS1 treatment suppressed AML cells proliferation, induced apoptosis, and mitochondrial damage, and elevated ROS levels. Network pharmacological analysis suggested, and subsequent studies confirmed, that TBMS1 induced mitophagy in AML cells by modulating the PINK1/Parkin/Mfnh2 signaling pathway, an effect that was effectively reversed following PINK1 knockdown. <em>In vivo,</em> TBMS1 treatment suppressed the proliferation of AML cells after 21 days, improved the survival rates of nude mice, and showed no evident organ toxicity. These evidences suggest that TBMS1 may have significant therapeutic potential in treating AML.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"55 ","pages":"Article 102355"},"PeriodicalIF":5.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671009","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":"Molecular profile of non-small cell lung cancer in a predominantly Black African population in Kenya: A single institution review","authors":"Sitna Mwanzi ,&nbsp;Shahin Sayed ,&nbsp;Swati Das ,&nbsp;Jonathan Wawire ,&nbsp;Priscilla Njenga ,&nbsp;Jasmit Shah ,&nbsp;Asim Jamal Shaikh","doi":"10.1016/j.tranon.2025.102348","DOIUrl":"10.1016/j.tranon.2025.102348","url":null,"abstract":"<div><h3>Introduction</h3><div>Targeted therapies for patients with non-small cell lung cancer (NSCLC) have significantly improved the outcomes for patients with oncogenic driver mutations. Testing for epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) rearrangement, c-ros oncogene 1 (ROS1) rearrangement and programmed death ligand 1 (PDL 1) testing are now highly recommended for all patients with NSCLC. There are clear geographical differences in the rate of driver mutations with higher EGFR mutation rates in the Asian population in comparison to the Caucasian population. Little is known about the rate of oncogenic driver mutations in predominantly Black African populations like those living in the East African region. This study describes the oncogenic driver mutations found in lung cancer patients diagnosed in a single institution in Kenya.</div></div><div><h3>Patients and methods</h3><div>We retrospectively reviewed the charts of patients who had a pathological diagnosis of NSCLC at Aga Khan University Hospital, Nairobi (AKUHN) between January 2012 and December 2022. Data was analyzed for socio-demographic characteristics, smoking status, clinical stage, histological sub-type and presence or absence of driver mutations.</div></div><div><h3>Results</h3><div>123 cases of non-small cell lung cancer (NSCLC) were included in the analysis. The median age at diagnosis was 62 years (IQR: 53.0 – 71.0) and 41.5 % (<em>n</em> = 51) of patients were under 60 years at time of diagnosis, 47.2 % (<em>n</em> = 58) were female and 78.9 % (<em>n</em> = 97) were of Black African descent. Only 29.4 % (<em>n</em> = 30) were known smokers whereas 73.2 % (<em>n</em> = 90) had stage IV disease. Adenocarcinoma was the most common sub-type in 85.4 % (<em>n</em> = 105) patients and 60 % of cases had EGFR testing done and a mutation was detected in 35 % (<em>n</em> = 26/74) patients tested. ALK and ROS rearrangement was positive in 19.5 % (<em>n</em> = 8/41) and 6.0 % (<em>n</em> = 2/33) patients tested respectively. Only 23.5 % (<em>n</em> = 8/34) of patients tested for PDL1 had an expression of &gt;1 %. There was no significant association between gender, ethnicity and smoking with EGFR mutation.</div></div><div><h3>Conclusion</h3><div>In our setting, EGFR testing was the most common molecular test done for lung cancer with a positive rate like that reported in Asian communities. Further studies are needed in a larger population to define further the molecular profile of lung cancer in Sub Saharan Africa. Access to testing will enhance targeted therapies for patients leading to improved outcomes.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"55 ","pages":"Article 102348"},"PeriodicalIF":5.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643720","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":"Frequent PD-L1 expression in oral squamous cell carcinoma of non-smokers and non-drinkers, and association of tumor infiltrating lymphocytes with favorable prognosis.","authors":"FJ Mulder ,&nbsp;EJ de Ruiter ,&nbsp;TFB Gielgens ,&nbsp;F Farshadpour ,&nbsp;R de Bree ,&nbsp;MFCM van den Hout ,&nbsp;B Kremer ,&nbsp;SM Willems ,&nbsp;EJM Speel","doi":"10.1016/j.tranon.2025.102357","DOIUrl":"10.1016/j.tranon.2025.102357","url":null,"abstract":"<div><h3>Objectives</h3><div>To determine the presence and prognostic value of PD-L1 and PD-L2 expression, and tumor-infiltrating lymphocytes (TILs) in oral squamous cell carcinoma (OSCC) of non-smokers and non-drinkers (NSND).</div></div><div><h3>Materials and methods</h3><div>Clinical characteristics and tumor tissue of 86 NSND with OSCC were retrospectively collected and analyzed for protein expression on tissue microarrays. Immunohistochemistry was performed for expression of PD-L1 CPS, PD-L2 TPS, and PD-1, CD45, CD8, CD4, CD3, and FoxP3-positive TILs/mm². Slides were digitally evaluated using QuPath. Differences in 5-year DFS and OS were determined by log rank analysis. Predictors for survival were determined by multivariable cox regression analysis.</div></div><div><h3>Results</h3><div>Eighty-eight percent (76/86) of OSCC showed PD-L1 expression (CPS ≥1). Patients with high numbers of CD4-positive TILs showed a better DFS and OS than patients with low numbers of CD4-positive TILs. In the best multivariable model, CD4-positive TILs were an independent predictor for DFS (<em>p</em> = 0.010) and OS (<em>p</em> = 0.002) too. Additionally, patients with high numbers of CD45-positive TILs and a high CD8/FoxP3 ratio showed a better OS, of which the CD8/FoxP3 ratio was a near significant independent predictor (<em>p</em> = 0.050). Over 40 % of OSCC were PD-L1+/TIL+.</div></div><div><h3>Conclusion</h3><div>A large number of OSCC in NSND show PD-L1 expression (CPS ≥1). CD4 was a significant predictor for DFS and OS, in addition to the CD8/FoxP3 ratio being a near significant predictor for OS. The combination of frequent high CD8-positive TIL infiltrates in PD-L1-positive tumors makes NSND with OSCC in theory interesting candidates for treatment with immune checkpoint inhibitors.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"55 ","pages":"Article 102357"},"PeriodicalIF":5.0,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629499","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":"Cardiotoxicity of breast cancer drug treatments","authors":"Maria Haque ,&nbsp;Nehal Atallah ,&nbsp;Rodhan Patke ,&nbsp;Anna E Harris ,&nbsp;Corinne L Woodcock ,&nbsp;Dhruvika Varun ,&nbsp;Rachel L Thompson ,&nbsp;Jorja Jackson-Oxley ,&nbsp;Cyntholia H Okui ,&nbsp;Alexander Dean ,&nbsp;Mansour Alsaleem ,&nbsp;Emad Rakha ,&nbsp;Sheeba Irshad ,&nbsp;Melissa B Davis ,&nbsp;Jennie N Jeyapalan ,&nbsp;Nigel P Mongan ,&nbsp;Catrin S Rutland","doi":"10.1016/j.tranon.2025.102352","DOIUrl":"10.1016/j.tranon.2025.102352","url":null,"abstract":"<div><div>Breast cancer (BC) is a leading cause of cancer-related mortality among women worldwide. BC is regarded as a systemic disease. Consequently, the majority of BC patients undergo systemic therapy to reduce the risk of distant metastasis (DM) and associated mortality. Although systemic therapies improve patients’ outcome, they are associated with significant side effects, particularly cardiotoxicity and cardiovascular complications. Such side effects vary significantly in severity and duration. Cardiotoxicity may remain undetected for years post-treatment until the symptoms of heart failure (HF) present in the patient, which can reduce life expectancy, quality of life, and even lead to death. Therefore, it is vital to investigate the cardiotoxic and cardiovascular risks of BC treatment regimens to identify patients who would benefit most from cardiac monitoring. As it stands, cardiotoxicity is reported from individual studies or for selected drug therapies only. This review fulfils a gap in the literature by combining clinical studies of cardiotoxicity together from clinical trial data published on clinicaltrials.gov.uk.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"55 ","pages":"Article 102352"},"PeriodicalIF":5.0,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628054","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":"Alteration in ATR protein level does not account for the inherent radiosensitivity of HPV-positive head and neck squamous cell carcinoma","authors":"Sibylla Kohl ,&nbsp;Florentine S.B. Subtil ,&nbsp;Vanessa Climenti ,&nbsp;Houmam Anees ,&nbsp;Ann C. Parplys ,&nbsp;Rita Engenhart-Cabillic ,&nbsp;Sebastian Adeberg ,&nbsp;Ekkehard Dikomey ,&nbsp;Ulrike Theiß","doi":"10.1016/j.tranon.2025.102359","DOIUrl":"10.1016/j.tranon.2025.102359","url":null,"abstract":"<div><h3>Objectives</h3><div>Human papilloma virus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) cells are highly radiosensitive resulting from an elevated number of DNA double-strand breaks (DSB) remaining after irradiation. Partially this effect is due to a defective homologous recombination (HR). HPV-positive cells also show pronounced instability of chromosome 3, which codes for the kinase ataxia-telangiectasia and Rad3-related (ATR) protein, a central player of HR. If there is a contribution of ATR to the radiosensitivity of HPV-positive cells remains unclear, and this in-vitro study tested a functional involvement of ATR expression.</div></div><div><h3>Methods</h3><div>The study was performed with six HPV-negative and six HPV-positive HNSCC cell lines. Gene copy number and gene expression were determined via qRT-PCR, protein expression by Western Blot. Response of cells towards irradiation in dependence of ATR expression was tested after siRNA Knock-down (ATRKD). Clonogenic survival after photon irradiation was evaluated by colony formation assay and DSBs were visualized by γH2AX/53BP1 co-staining.</div></div><div><h3>Results</h3><div>ATR gene copy number and expression were not altered. Protein level was almost two-fold lower in HPV-positive compared to HPV-negative cells, but fully functional as observed by active phosphorylation in response towards irradiation. ATRKD resulted in a further increase in both, radiosensitivity as well as number of residual DSBs, but only for HPV-positive cells.</div></div><div><h3>Conclusion</h3><div>Since the effect of ATRKD was compensated in HPV-negative but not in HPV-positive cells, these data revealed that the two-fold lower level of ATR in HPV-positive cells does not account for their enhanced inherent radiosensitivity, but acts additive to irradiation.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"55 ","pages":"Article 102359"},"PeriodicalIF":5.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620065","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":"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}