Translational Oncology最新文献

{"title":"Exploration of precise classification and therapeutic targets of breast cancer based on genes related to neuro-cancer crosstalk","authors":"Zhi Li ,&nbsp;Chang Sun ,&nbsp;Yangyang Cui ,&nbsp;Yue Huang ,&nbsp;Mingduo Liu ,&nbsp;Hui Xie ,&nbsp;Shui Wang","doi":"10.1016/j.tranon.2025.102647","DOIUrl":"10.1016/j.tranon.2025.102647","url":null,"abstract":"<div><div>This investigation examines neural-cancer crosstalk in breast cancer, utilizing TCGA/GEO transcriptomic and single-cell data to develop a neural-cancer crosstalk prognostic signature and evaluate its clinical relevance. We identified four core genes—L1CAM, TACR1, GFRA1, and NTRK3—using univariate Cox regression and LASSO-Cox regression to develop a risk scoring model. The prognostic signature showed consistent predictive accuracy across validation cohorts, with high-risk patients demonstrating markedly reduced survival. Multivariate analysis established the risk score as an independent prognostic indicator. Immune profiling identified an immunosuppressive phenotype in high-risk cases, featuring elevated Treg infiltration and impaired antigen presentation. Genomic analysis revealed significantly higher TP53 mutation frequency in high-risk versus low-risk patients. Drug sensitivity predictions indicated that the high-risk group exhibited increased sensitivity to targeted therapies such as Lapatinib, but enhanced resistance to conventional chemotherapy. Single-cell sequencing revealed the heterogeneity of breast cancer cells and elucidated a neuro-immune-tumor interaction network dominated by MIF and MDK signaling pathways. Functional validation studies demonstrated that L1CAM knockdown effectively suppressed malignant phenotypes in breast cancer cells, including proliferation, migration, and invasive capacity in vitro. This study provides new insights into the regulatory mechanisms of the neural microenvironment in breast cancer, and the established prognostic model and identified potential therapeutic targets hold significant clinical implications for personalized treatment.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102647"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circular RNA circSCMH1 regulates glycolysis to inhibit gastric cancer metastasis via miR-296–3p/HSPB7-GLUT3 axis","authors":"Yue Yang ,&nbsp;Qiushuang Wang ,&nbsp;Zhe Gong ,&nbsp;Jinsi Chen ,&nbsp;Ya’nan Yang ,&nbsp;Liqin Zhao ,&nbsp;Yujia Zhai ,&nbsp;Ting Zhao ,&nbsp;Wenfang Du ,&nbsp;Jieyun Zhang ,&nbsp;Weijian Guo","doi":"10.1016/j.tranon.2025.102644","DOIUrl":"10.1016/j.tranon.2025.102644","url":null,"abstract":"<div><div>Metastasis is main reason leading to gastric cancer (GC) caused death. GC metastasis is known to be associated with complex factors, of which circular RNAs (circRNAs) become hot molecules recently. How to effectively select key molecules participating in GC metastasis is still needing to be resolved. Through next-generation sequencing, metastasis-driven circRNAs were selected by comparing cancer and para-cancer tissues from GC patients with different metastasis tendency. The biological function of circSCMH1 was identified in vivo and in vitro. Through luciferase reporter system and functional rescue test, the downstream microRNA and target gene were identified. Glucose uptake, lactic acid production and ATP production were detected to estimate glycolysis level. Moreover, 110 GC samples were collected and following clinical association analysis was conducted. circSCMH1 showed significantly lower expression in high-metastasis GC. circSCMH1 could suppress glycolysis to inhibit GC proliferation and metastasis in vivo and in vitro, and played its biological function through miR-296–3p/HSPB7-GLUT3 axis. circSCMH1 showed closely association with GC lymph node metastasis and prognosis. circSCMH1 could inhibit gastric cancer metastasis through regulating glycolysis via miR-296–3p/HSPB7-GLUT3 axis. circSCMH1 could become potential biomarker for GC lymph node metastasis and even therapeutic target in the future.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102644"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145769320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A monoclonal antibody targeting B7-H3 in human embryonic stem cells exhibits anti-tumor activity in hepatocellular carcinoma xenografts","authors":"San Ha Han ,&nbsp;Hyosun Seo ,&nbsp;Ji Yoon Lee ,&nbsp;Yoo Jin Cheon ,&nbsp;Sein Han ,&nbsp;Mun Ju Choi ,&nbsp;Hyun Min Lee ,&nbsp;Dae Shick Kim ,&nbsp;Dongho Choi ,&nbsp;Chun Jeih Ryu","doi":"10.1016/j.tranon.2025.102638","DOIUrl":"10.1016/j.tranon.2025.102638","url":null,"abstract":"<div><div>B7-H3 is highly expressed with limited heterogeneity in various cancer types including hepatocellular carcinoma (HCC) but shows low expression in normal tissues. We generated monoclonal antibodies (MAbs) against surface molecules on human embryonic stem cells (hESCs) and found that NPB40, one of the MAbs, binds to HCC cells, but only weakly to primary hepatocytes. Immunoprecipitation with mass spectrometry identified that NPB40 recognizes B7-H3. In tumorsphere cultures, the expression of B7-H3 interacting with NPB40 was significantly increased, as were known cancer stem cell (CSC) markers. After cell sorting by NPB40, NPB40-high HCC cells showed higher clonogenic survival than NPB40-low HCC cells, suggesting B7-H3 as a potential CSC marker on HCC cells. NPB40 and Chi-NPB40, a chimeric form of NPB40, induced internalization of B7-H3 and inhibited cell proliferation of HCC cells by toxic payload delivery via anti-human secondary antibody drug conjugates (ADCs) and Chi-NPB40 was able to induce antibody-dependent cellular cytotoxicity (ADCC) against HCC cells <em>in vitro</em>. NPB40 and Chi-NPB40 injection also suppressed tumor growth in a xenograft nude mouse model of HCC. The results suggest that NPB40 may be developed as a therapeutic antibody for HCC patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102638"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of a TOP2A based index clinical model for kidney renal clear cell carcinoma","authors":"Xiaodong Shi ,&nbsp;Baiyang Song ,&nbsp;Boqian Wang ,&nbsp;Anyi Chen ,&nbsp;Jiasheng Hu ,&nbsp;Guohai Xie ,&nbsp;Jialing Huang ,&nbsp;Caiyun Huang ,&nbsp;Yue Cheng ,&nbsp;Zejun Yan ,&nbsp;Wei Du","doi":"10.1016/j.tranon.2025.102625","DOIUrl":"10.1016/j.tranon.2025.102625","url":null,"abstract":"<div><h3>Objective</h3><div>TOP2A (Topoisomerase II alpha) is significantly overexpressed in kidney renal clear cell carcinoma (KIRC), and its expression level is significantly associated with accelerated tumor progression and poor prognosis in patients. Therefore, the aim of this study is to systematically analyze the biological functions of TOP2A-related molecular markers in KIRC by constructing a TOP2A based index clinical model. Additionally, we aim to screen potential therapeutic targets to guide the optimization of clinical intervention strategies.</div></div><div><h3>Methods</h3><div>Integrated TCGA-KIRC data were standardized and analyzed via PCA. Differentially expressed genes between TOP2A high/low expression groups were screened and functionally annotated (GO/KEGG). WGCNA identified core TOP2A-associated modules, combined with Cox regression to construct a prognostic model. GSEA evaluated pathway activity, immune infiltration, and immune checkpoint correlations. Regulatory networks (miRNA/lncRNA/RBP), mutation profiles, and methylation-transcriptome interactions were explored.</div></div><div><h3>Results</h3><div>5500 TOP2A-related deregulated genes were identified, with core modules enriched in cell cycle/DNA replication pathways. The TOP2A-index model inversely correlated with patient survival. High TOP2A expression scores showed positive associations with immune checkpoint genes. Multi-omics analyses revealed global regulatory networks linking TOP2A to tumor microenvironment modulation.</div></div><div><h3>Conclusion</h3><div>This study developed a TOP2A based index clinical model that will aid in predicting the prognosis of KIRC patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102625"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The CHPT-pSTAT3-SLC7A11 signaling axis controls progression and ferroptosis susceptibility of pancreatic cancer","authors":"Jianhui Yang ,&nbsp;Jiang Liu ,&nbsp;Zeyin Rong ,&nbsp;Zhen Tan ,&nbsp;Wei Wang ,&nbsp;Qingcai Meng ,&nbsp;Miaoyan Wei ,&nbsp;Jie Hua ,&nbsp;Bo Zhang ,&nbsp;Xianjun Yu ,&nbsp;Jin Xu ,&nbsp;Chen Liang","doi":"10.1016/j.tranon.2025.102624","DOIUrl":"10.1016/j.tranon.2025.102624","url":null,"abstract":"<div><h3>Background</h3><div>Pancreatic ductal adenocarcinoma (PDAC) exhibits profound chemoresistance and metastasis, driving its dismal prognosis. Gemcitabine (GEM) resistance remains a critical barrier, necessitating exploration of metabolic regulators like choline phosphotransferase 1 (CHPT1) and ferroptosis in PDAC therapy.</div></div><div><h3>Method</h3><div>GEM-resistant PDAC cells were generated through stepwise induction. Metabolomics, RNA sequencing, and functional assays (CCK-8, EdU, Transwell) identified CHPT’s role. CHPT1 and SLC7A11 were genetically modulated using lentiviral vectors. Xenograft models assessed tumor growth.</div></div><div><h3>Results</h3><div>CHPT1 was downregulated in PDAC tissues and GEM-resistant cells. Restoring CHPT1 suppressed proliferation, migration, and epithelial–mesenchymal transition while enhancing GEM sensitivity. Mechanistically, CHPT1 recruited phosphatase PTPN1 to dephosphorylate STAT3 at Y705, inhibiting SLC7A11 transcription and triggering ferroptosis via lipid peroxidation. PTPN1 knockdown abolished CHPT1’s tumor-suppressive effects. Combining ferroptosis inducers (e.g., Erastin) with GEM synergistically inhibited tumor growth in vitro and in vivo.</div></div><div><h3>Conclusion</h3><div>The CHPT1-pSTAT3-SLC7A11 axis governs ferroptosis-dependent chemoresistance in PDAC. Dual targeting of CHPT1 and ferroptosis pathways represents a promising strategy to overcome GEM resistance, highlighting metabolic-kinase crosstalk as a therapeutic vulnerability.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102624"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145669829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of local recurrence in cohorts of head and neck cancer patients after intensity-modulated radiation therapy based on CT radiomics: A double-center observation study","authors":"Jing Xu,&nbsp;Qing Liu,&nbsp;Yue Yin,&nbsp;Junhang Gao,&nbsp;Guanglu Dong","doi":"10.1016/j.tranon.2025.102622","DOIUrl":"10.1016/j.tranon.2025.102622","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to develop and validate a CT-based radiomics model for predicting the prognosis of head and neck cancer patients, particularly those with nasopharyngeal carcinoma (NPC), following intensity-modulated radiation therapy (IMRT).</div></div><div><h3>Methods</h3><div>We conducted a retrospective analysis involving 392 pathologically confirmed NPC patients from two centers. Center A contributed 226 patients to the training cohort, while Center B provided 64 patients for the validation cohort. Features extracted from CT images were utilized to develop two predictive models: a clinically combined radiomics model and a standalone radiomics model. Dimensionality reduction and nested cross-validation were employed in the model development process. The performance of the models was assessed and validated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA), with differences between the models evaluated using the DeLong test.</div></div><div><h3>Results</h3><div>Our findings indicate that the clinically combined radiomics model outperforms the standalone radiomics model in prognostic prediction. The area under the curve (AUC) for the combined model was 0.90 in the training cohort, while the validation cohort achieved an AUC of 0.86. DCA further confirmed that the performance of all models exceeded that of blindly predicting patient outcomes as either all negative or all positive. Subsequent comparisons using the DeLong test revealed significant differences in predictive performance between the standalone radiomics model and the clinically combined radiomics model, with P-values &lt;0.05.</div></div><div><h3>Conclusion</h3><div>The clinically combined radiomics model demonstrates promising performance in predicting the prognosis of NPC patients following IMRT.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102622"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145669760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nutritional strategies against skeletal muscle wasting in cancer-associated cachexia: the role of β-hydroxybutyrate and polyunsaturated fatty acids","authors":"Benjamin Hay ,&nbsp;Aurélien Brun ,&nbsp;Anne Fougerat ,&nbsp;Vera Mazurak ,&nbsp;Olivier Le Bacquer ,&nbsp;Jérémie Talvas ,&nbsp;Frédéric Capel","doi":"10.1016/j.tranon.2025.102596","DOIUrl":"10.1016/j.tranon.2025.102596","url":null,"abstract":"<div><div>Cachexia is a multifactorial syndrome that occurs in many cancers, particularly in their advanced stages, decreasing the quality of life and lifespan of patients. One of the hallmarks of cancer-associated cachexia is skeletal muscle wasting. Multiple causes include inflammation, metabolic deregulation, energy utilization, endoplasmic reticulum and oxidative stress. Loss of skeletal muscle is characterised by an imbalance in protein homeostasis, with decreased anabolism (regulated by the Akt/GSK3/eIF2α and Akt/mTORC1 pathways) and increased catabolism (regulated by autophagy and the ubiquitin-proteasome system), as well as an impairment in myogenesis. Accumulating evidence suggests that dietary intervention of β-hydroxybutyrate, the major ketone body produced by ketogenesis, and n-3 polyunsaturated fatty acids may mitigate skeletal muscle wasting. Polyunsaturated fatty acids and β-hydroxybutyrate are able to favourably modulate inflammation, insulin resistance, unfolded protein response and stresses (such as metabolic stress and oxidative stress). A well-adapted nutritional strategy may include a “classic” diet supplemented with β-hydroxybutyrate and polyunsaturated fatty acids to maintain skeletal muscle integrity and reduce wasting.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102596"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145496962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aurintricarboxylic acid, an inhibitor of cystathionine γ-lyase, enhances the sensitivity of chemotherapy drugs in TNBC","authors":"Xue Han ,&nbsp;Han Fu ,&nbsp;Zhenshuai Zhang ,&nbsp;Jian Wang ,&nbsp;Shasha Feng ,&nbsp;Li Jiang ,&nbsp;Lu Chen ,&nbsp;Hui Li ,&nbsp;Tianxiao Wang","doi":"10.1016/j.tranon.2025.102602","DOIUrl":"10.1016/j.tranon.2025.102602","url":null,"abstract":"<div><div>The current treatments for triple-negative breast cancer (TNBC) rely mainly on chemotherapy. Enhancing the effect of chemotherapy drugs or exploring new targeted drugs is expected to provide more treatment options for patients with TNBC. Our previous studies have shown that the cystathionine-γ-lyase (CSE) plays an important role in the progression of TNBC. So inhibition of CSE may provide a new direction for the treatment of TNBC. This study aimed to explore the relationship between CSE expression and chemotherapy drug sensitivity, as well as the potential therapeutic role of CSE inhibitor Aurintricarboxylic acid (ATA) in TNBC. The results suggest that the expression of CSE is negatively correlated with the sensitivity of chemotherapy drugs and changes in CSE levels affect the sensitivity of chemotherapy drugs in TNBC cells. The CSE inhibitor ATA has significantly enhanced the sensitivity of chemotherapeutic drugs in MDA-MB-231 cells and 4T1 mouse transplanted tumor model. Further mechanism research has found that ATA enhances the sensitivity of chemotherapeutic drugs via SIRT1-STAT3-C-myc-Bcl-2 signaling pathway in TNBC cells. In addtion, ATA also enhances the sensitivity of chemotherapeutic drugs in TNBC cells by regulating the expression of P-glycoprotein (P-gp), glutathione (GSH) and reactive oxygen species (ROS). These findings suggest that ATA may be a promising therapeutic agent for TNBC treatment by enhancing the sensitivity of chemotherapy drugs through multiple mechanisms.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102602"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145557766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel NOTCH2-NTRK1 fusion confers osimertinib resistance in EGFR-mutant non-small cell lung cancer by interacting with EGFR","authors":"Hui Li ,&nbsp;Huiting Wei ,&nbsp;Tiantian Zhen ,&nbsp;Huabin Gao ,&nbsp;Huicong Liu ,&nbsp;Shuai Zheng ,&nbsp;Huijuan Shi ,&nbsp;Jiangtao Liang ,&nbsp;Fenfen Zhang ,&nbsp;Jiecheng Ye ,&nbsp;Gengpeng Lin ,&nbsp;Anjia Han","doi":"10.1016/j.tranon.2025.102577","DOIUrl":"10.1016/j.tranon.2025.102577","url":null,"abstract":"<div><h3>Background</h3><div>Overcoming osimertinib resistance in epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) is challenging due to unclear mechanisms. We previously reported a NSCLC case with EGFR mutations progressed on osimertinib therapy, revealing a novel NOTCH2-NTRK1 fusion gene in the plasma and tumor tissue. Although the NTRK gene fusion has been identified in NSCLC and a range of tumor types, the role of NOTCH2-NTRK1 in osimertinib resistance is unclear.</div></div><div><h3>Methods</h3><div>We utilized both in vitro and in vivo models exhibiting NOTCH2-NTRK1 fusion positivity to explore the biological function of NOTCH2-NTRK1, as well as its role and mechanism in osimertinib resistance.</div></div><div><h3>Results</h3><div>The NOTCH2-NTRK1 fusion protein has been demonstrated to transform the human bronchial epithelial cell line BEAS-2B and promote the proliferation of NSCLC cells both in vitro and in vivo. It induces osimertinib resistance by activating MAPK and PI3K-AKT pathways. Phosphoproteomic analyses revealed a significant increase in the phosphorylation level of EGFR compared to the control group. Further investigations demonstrated that the NOTCH2-NTRK1 protein is capable of interacting with the EGFR protein. Protein molecular docking studies identified seven interacting sites between NOTCH2-NTRK1 and EGFR protein. Mutations within the region encompassing these seven interaction sites effectively reversed osimertinib resistance, leading to a significant reduction in the expression of key proteins within the MAPK and PI3K-AKT pathways. Notably, the interaction between NOTCH2-NTRK1 and EGFR was maintained even with combined osimertinib and entrectinib treatment.</div></div><div><h3>Conclusion</h3><div>Our study reveals a novel mechanism by which the NOTCH2-NTRK1 fusion confers resistance to osimertinib through its interaction with EGFR in NSCLC.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102577"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145606189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prognostic value of tumor macroscopic morphology in colorectal cancer","authors":"Hsinyi Lin ,&nbsp;Zimin Zhao ,&nbsp;Yao Ma ,&nbsp;Xiangchao Shi ,&nbsp;Limei Guo ,&nbsp;Junwei Wang ,&nbsp;Wei Fu ,&nbsp;Xin Zhou","doi":"10.1016/j.tranon.2025.102607","DOIUrl":"10.1016/j.tranon.2025.102607","url":null,"abstract":"<div><h3>Background</h3><div>This study aims to evaluate the prognostic value of tumor macroscopic morphology in colorectal cancer (CRC) and understand the molecular mechanism behind different tumor morphologies.</div></div><div><h3>Methods</h3><div>642 eligible patients were enrolled in this study, including 335 patients in the prospective study and 307 patients in the retrospective study. CRCs were categorized into protruded, ulcerative, and infiltrative types according to our morphological classification, and their clinicopathological features and prognosis were analyzed. Furthermore, bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq) and immunohistochemistry were performed to map the tumor microenvironment of different tumor morphologies.</div></div><div><h3>Results</h3><div>In the prospective cohort, CRC with infiltrative type were significantly associated with unfavorable clinicopathological characteristics and poor survival compared with ulcerative type and protruded type. Bulk RNA sequencing revealed that the infiltrative type correlated with higher expression of fibroblast activation protein-α (FAP), periostin and platelet endothelial cell adhesion molecule-1 (PECAM-1), which corresponded with elevated cell proportions of stromal cells and endothelial cells in scRNA-seq. Additionally, a retrospective cohort was conducted to assess the value of preoperative endoscopic morphology and radiological morphology, both independently associated with disease-free survival (DFS).</div></div><div><h3>Conclusion</h3><div>We proposed a revised tumor macroscopic morphology classification system in CRC. The infiltrative type is associated with poorer clinical outcomes, characterized by increased cancer-associated fibroblast (CAF) infiltration and enhanced angiogenesis compared with other types. Importantly, when expanded to endoscopy and CT preoperatively, both endoscopic and radiological morphology can serve as preoperative predictors of DFS.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102607"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}