Journal of CancerPub Date : 2025-04-13eCollection Date: 2025-01-01DOI: 10.7150/jca.106902
Sachin Kumar, Chung-Che Wu, Fitria Sari Wulandari, Chung-Chieh Chiao, Ching-Chung Ko, Hung-Yun Lin, Juan Lorell Ngadio, Cathleen Rebecca, Do Thi Minh Xuan, Dahlak Daniel Solomon, Michael Michael, Lidya Kristiani, Jian-Ying Chuang, Ming-Cheng Tsai, Chih-Yang Wang
{"title":"Integration of multi-omics and single-cell transcriptome reveals mitochondrial outer membrane protein-2 (MTX-2) as a prognostic biomarker and characterizes ubiquinone metabolism in lung adenocarcinoma.","authors":"Sachin Kumar, Chung-Che Wu, Fitria Sari Wulandari, Chung-Chieh Chiao, Ching-Chung Ko, Hung-Yun Lin, Juan Lorell Ngadio, Cathleen Rebecca, Do Thi Minh Xuan, Dahlak Daniel Solomon, Michael Michael, Lidya Kristiani, Jian-Ying Chuang, Ming-Cheng Tsai, Chih-Yang Wang","doi":"10.7150/jca.106902","DOIUrl":"https://doi.org/10.7150/jca.106902","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) remains to be one of the most prevalent and highly invasive forms of cancer. Mitochondrial outer membrane protein-2 or Metaxin-2 (MTX2), a key regulator of mitochondrial function, has been linked to cellular bioenergetics and stress response mechanisms. However, its roles in the progression and prognosis of LUAD remain largely unexplored. This study, employed a multi-omics approach, integrating transcriptomic and clinical patient data from public databases, to evaluate the expression and prognostic relevance of MTX2 in LUAD. Single-cell RNA sequencing was utilized to further explore MTX2's role in immune infiltration and interactions within the tumor microenvironment. Additionally, we validated these findings through a series of molecular biology and functional assays. Our results demonstrated that MTX2 expression was higher in LUAD tissues compared to normal lung tissues. Elevated MTX2 levels were significantly associated with poorer overall survival in LUAD patients. Functional analyses revealed that MTX2 regulates mitochondrial bioenergetics and facilitates tumor cell proliferation. Additionally, MTX2 expression was associated with increased immune cell infiltration. A pathway analysis identified cell metabolic and tumor growth pathways regulated by MTX2, supporting its role in tumor progression. Our research identifies MTX2 as a promising prognostic biomarker and therapeutic target for LUAD. Increased expression of MTX2 promotes tumor growth by altering metabolic pathways and modulating the immune response, underscoring its potential as a new target for LUAD treatment.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 7","pages":"2401-2420"},"PeriodicalIF":3.3,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Construction of a Prognostic Model based on CSC-related Genes in Patients with Colorectal Cancer.","authors":"Zi-Yue Li, Ming-Feng Li, Ying-Ying He, Guan-Sheng Zheng, Jie-Rong Chen, Yun-Miao Guo, Qizhou Lian, Cai-Feng Yue","doi":"10.7150/jca.108188","DOIUrl":"https://doi.org/10.7150/jca.108188","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is one of the most common and deadly malignancies. Lack of efficient biomarkers for prognosis has limited the improvement of survival outcome in patients with CRC. Numerous studies have demonstrated the important roles of cancer stem cells (CSCs) in both treatment resistance and disease recurrence of CRC. Thus, the current study aims to construct a prognostic model based on expression level of CSC-related genes for precise molecular subtyping of CRC patients with different prognoses, TME infiltration patterns and therapeutic responses. The RNA sequencing data and clinical information were obtained from UCSC Xena database, followed by identification of differential expressed genes, univariate Cox regression, and LASSO regression to identify prognostic CSC-related genes and construct a novel prognostic risk scoring model consisting of 21 CSC-related genes. The patients in high-risk group suffered poor survival outcome (<i>P</i><0.0001). Moreover, the performance of CSC-related prognostic model was validated in individual GEO datasets including GSE41258 and GSE39582 (<i>P</i><0.05). Furthermore, patients with high-risk score exhibited lower response rate to immune checkpoint inhibitors as compared to those in low-risk group (17.4% vs. 28.2%), indicating the potential of CSC-related prognostic model to predict the immunotherapy response. Collectively, our findings provide an effective model to predict the immunotherapy response and survival outcome in patients with CRC.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 7","pages":"2375-2387"},"PeriodicalIF":3.3,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of CancerPub Date : 2025-04-13eCollection Date: 2025-01-01DOI: 10.7150/jca.103286
Qiang Xue, Ruicong Ma, YueYuan Chen, Xiaodi Yan, Jiajia Liu, Jianhua Xue, Yang Yang, Xianchen Liu
{"title":"MiR-371b-5p reduces osteosarcoma cell migration and proliferation to induce apoptosis by targeting FUT4.","authors":"Qiang Xue, Ruicong Ma, YueYuan Chen, Xiaodi Yan, Jiajia Liu, Jianhua Xue, Yang Yang, Xianchen Liu","doi":"10.7150/jca.103286","DOIUrl":"https://doi.org/10.7150/jca.103286","url":null,"abstract":"<p><p>In our previous study (PMID: 34671604), we found that miR-317b-5b not only exerted anti-tumor effect, but also downregulated FUT4 expression in human myeloma cell line 143B. This study aims to investigate the biological function of miR-371b-5p in osteosarcoma progression and the role of FUT4 in this process. For <i>in vitro</i> investigations, the human osteosarcoma cell lines (SaOS2, 143B, KHOS and U2OS) as well as the human osteoblast cell line (hFOB1.19) were employed as models. The QRT-PCR assay was utilized to determine the relative amounts of miR-371b-5p and FUT4 expression in the cells. The functions and effects of miR-371b-5p on the abilities to proliferate, migrate, apoptosis and invade of KHOS and U2OS in osteosarcoma cells were investigated using assays including CCK-8, colony formation, EDU, wound-healing, Western blot, TUNEL and Transwell assay. The correlations between miR-371b-5p, its downstream gene FUT4 and its potential mechanisms in mediating osteosarcoma progression were explored with the assistance of dual-luciferase reporter analysis together with rescue experiments. MiR-371b-5p was less expressed in osteosarcoma cells compared with osteoblasts. Its overexpression significantly inhibited the abilities to proliferate, invade and migrate to promote apoptosis of osteosarcoma cells. The correlations between FUT4 and miR-371b-5p was established by the gene analysis of the dual-luciferase reporter analysis. FUT4 expression was dramatically decreased after the process of miR-371b-5p mimics being transfected into KHOS and U2OS cells. Additionally, overexpression of FUT4 induced osteosarcoma cell apoptosis and partially overcame miR-371b-5p's inhibitory effects on osteosarcoma cell's abilities to proliferate, invade and migrate. Osteosarcoma cells exhibit down-regulation of miR-371b-5p, that prevents osteosarcoma cells from proliferating, invading and migrating in order to promote osteosarcoma cell apoptosis through concentrating on the breakdown of FUT4.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 7","pages":"2388-2400"},"PeriodicalIF":3.3,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identification of the role of MED6 in the development and prognosis of lung adenocarcinoma based on multi-omics profiling.","authors":"Changqing Yang, Ding Cheng, Shuo Wang, Baichuan Wang, Yingxi Li, Guixin Wang, Xingkai Wang, Cangchang Shi, Yao Tian, Keyun Zhu, Jing Feng","doi":"10.7150/jca.110981","DOIUrl":"https://doi.org/10.7150/jca.110981","url":null,"abstract":"<p><p><b>Background:</b> Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. Recent studies have highlighted the importance of Mediator complex subunits in cancer, but their specific roles in LUAD are still unclear. <b>Methods:</b> The CRISPR-Cas9 loss-of-function data was used to assess gene dependency in cell growth. RNA-seq data were analyzed to evaluate the prognostic value of Mediator subunits and explore their downstream pathways. Single-cell sequencing data were utilized to examine the tumor microenvironment in LUAD. A drug sensitivity analysis was performed to identify potential therapeutic options. <b>Results:</b> Mediator complex subunit 6 (MED6) was found to influence tumor cell growth in LUAD. Additionally, MED6 expression levels were associated with patient prognosis. MED6-positive tumor cells showed more active interactions with other cells in the LUAD microenvironment, promoting tumor progression. Based on MED6 expression, drugs such as paclitaxel, afatinib, and brivanib were identified as potential treatments. <b>Conclusions:</b> This study revealed the role of MED6 in LUAD and its potential as a biomarker. Our findings suggest that MED6 has an effect on LUAD progression and provide valuable insights for patient stratification and personalized treatment strategies.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 7","pages":"2362-2374"},"PeriodicalIF":3.3,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Erratum: Co-delivery of Cyclopamine and Doxorubicin Mediated by Bovine Serum Albumin Nanoparticles Reverses Doxorubicin Resistance in Breast Cancer by Down-regulating P-glycoprotein Expression: Erratum.","authors":"Yong-Lin Lu, Ya-Bin Ma, Chan Feng, Dong-Lei Zhu, Jie Liu, Lv Chen, Shu-Jing Liang, Chun-Yan Dong","doi":"10.7150/jca.113959","DOIUrl":"https://doi.org/10.7150/jca.113959","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.7150/jca.30323.].</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 7","pages":"2360-2361"},"PeriodicalIF":3.3,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"<i>SF3a1</i>: A Novel Potential Tumor Biomarker or Therapeutic Target.","authors":"Xueqian Shuai, Yaoqi Sun, Shupeng Liu, Zhongping Cheng","doi":"10.7150/jca.103209","DOIUrl":"https://doi.org/10.7150/jca.103209","url":null,"abstract":"<p><p>Alternative splicing is an evolutionarily conserved and essential cellular process that is catalyzed by a multi-complex spliceosome. Dysregulation of this process has been implicated in various tumors over the recent years. <i>SF3a1</i> is a critical subunit of U2 small nuclear ribonucleoprotein (snRNP) in the spliceosome, which has been found to be aberrant in several human diseases. Recent reports suggest that <i>SF3a1</i> might be a novel therapeutic target. However, a comprehensive description of <i>SF3a1</i> is lacking. In this review, we present the findings of <i>SF3a1</i> from protein structure, biological function to strong associations with human diseases including cancer. Studies have reported that <i>SF3a1</i> dysregulation and associated alternative splicing events mediate tumorigenesis and other immune-related disorders. However, further functional and mechanistic studies are needed to fully understand the regulatory network of <i>SF3a1</i> in human diseases. In conclusion, <i>SF3a1</i> could serve as a promising prognostic biomarker and therapeutic target for specific cancer types, including prostate cancer, colorectal cancer and hepatocellular carcinoma.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 7","pages":"2353-2359"},"PeriodicalIF":3.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nano-strategies for Targeting Tumor-Associated Macrophages in Cancer immunotherapy.","authors":"Qian Li, Jingwei Xu, Runjia Hua, Hanye Xu, Yongyou Wu, Xiaju Cheng","doi":"10.7150/jca.108194","DOIUrl":"https://doi.org/10.7150/jca.108194","url":null,"abstract":"<p><p>Tumor-associated macrophages (TAMs) are one type of the most abundant immune cells within tumor, resulting in immunosuppresive tumor microenvironment and tumor resistance to immunotherapy. Thus, targeting TAMs is a promising therapeutic strategy for boosting cancer immunotherapy. This study provides an overview of current therapeutic strategies targeting TAMs, which focus on blocking the recruitment of TAMs by tumors, regulating the polarization of TAMs, and directly eliminating TAMs using various nanodrugs, especially with a new categorization based on the specific signaling pathways, such as NF-κB, HIF-1α, ROS, STAT, JNK, PI3K, and Notch involved in their regulatory mechanism. The latest developments of nanodrugs modulating these pathways are discussed in determining the polarization of TAMs and their role in the tumor microenvironment. Despite the challenges in clinical translation and the complexity of nanodrug synthesis, the potential of nanodrugs in enhancing the effectiveness of cancer immunotherapy is worthy of expecting.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 7","pages":"2261-2274"},"PeriodicalIF":3.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"circ_0046599 Promotes HCC Progression by Competing with miR-1322 to Enhance NT5DC2 Expression.","authors":"Xiaobo Zhang, Suxin Li, Luhao Li, Dingyang Li, Huashan Zhao, Xiaole Gao, Xiaowei Dang","doi":"10.7150/jca.103661","DOIUrl":"https://doi.org/10.7150/jca.103661","url":null,"abstract":"<p><p><b>Background</b>: This study aimed to investigate the impact of circ_0046599 on hepatocellular carcinoma (HCC). <b>Methods:</b> Analysis of the GEO dataset identified circ_0046599 as significantly upregulated in HCC, and its impact on cell proliferation, apoptosis, migration, and invasion was assessed. Bioinformatics and dual-luciferase assays identified miR-1322 as a target of circ_0046599, which in turn regulates NT5DC2 expression. In vitro and in vivo experiments confirmed the ceRNA mechanism of circ_0046599 in HCC. <b>Results:</b> circ_0046599 was significantly upregulated in HCC, and predicts a worse survival in HCC patients. Increased expression of circ_0046599 promoted HCC cell proliferation, migration, invasion, and inhibited apoptosis. circ_0046599 bound to miR-1322, which exerted a tumor-suppressive effect in HCC cells. miR-1322 targeted NT5DC2, and circ_0046599 regulated the expression of NT5DC2 by competitively binding to miR-1322. Modulation of NT5DC2 expression affected the oncogenic role of circ_0046599. In <i>in vivo</i> experiments, inhibition of circ_0046599 suppressed the growth of xenograft tumors by upregulating miR-1322 expression and suppressing NT5DC2. <b>Conclusion</b>: circ_0046599 promoted the progression of HCC by competitively binding to miR-1322 and regulating the expression of NT5DC2.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 7","pages":"2275-2288"},"PeriodicalIF":3.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of Exercise Intensity and Time on Efficacy of Paclitaxel and Doxorubicin and Immune Microenvironment in the 4T1 Breast Cancer Model.","authors":"Liang Zhou, Yonghong Yang, Xiang Luo, Xinling Gan, Chengqi He, Yong Xia, Siyi Zhu","doi":"10.7150/jca.105352","DOIUrl":"https://doi.org/10.7150/jca.105352","url":null,"abstract":"<p><p><b>Background</b>: Chemotherapy is the mainstay treatment for metastatic triple negative breast cancer (TNBC). However, many patients still die of metastasis after chemotherapy, making it worthwhile to develop strategies to increase chemotherapy efficacy when treating metastatic TNBC. Previous studies have shown that exercise has the potential to inhibit breast cancer metastasis and enhance the effect of chemotherapy, and the level of exercise had a significant effect on tumor metastasis. However, the effect of different doses of exercise-referring to the combination of intensity and duration-on tumor metastasis during breast cancer chemotherapy remains unclear. <b>Methods</b>: 4T1 TNBC subcutaneous tumors were treated with paclitaxel (PTX) and doxorubicin hydrochloride (DOX), as well as different intensities and duration of exercise. Tumor growth, survival, metastatic burden, and the frequencies of some important immune cells were measured to determine the effects, and underlying mechanism, of different exercise doses on the anti-cancer efficacy of PTX and DOX. <b>Results</b>: The combination of high-dose exercise with PTX and DOX promoted metastasis formation, shortened mouse survival, and up-regulated the neutrophil/T lymphocyte ratio in the lungs. In contrast, low-dose exercise synergized with PTX and DOX to suppress metastasis, prolonged the survival of mice, decreased the neutrophil/T lymphocyte ratio, and up-regulated the percentages of NK cells within the metastatic microenvironment. The combination of different exercise dose with PTX and DOX did not affect primary tumor growth. <b>Conclusions</b>: The intensity and time of exercise might affect efficacy of PTX and DOX; however, TNBC patients should be careful concerning the intensity and time of exercises while undergoing chemotherapy. Breast cancer patients might be best served by participating in low levels of exercise, and avoiding excessive exercise, during PTX and DOX therapy.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 7","pages":"2298-2311"},"PeriodicalIF":3.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of CancerPub Date : 2025-03-31eCollection Date: 2025-01-01DOI: 10.7150/jca.108685
Danqing Zhu, Keyi Shi, Dongxiao Hu, Wanrun Lin, Xiaofei Zhang, Feng Zhou, Yang Li
{"title":"Clinicopathological and Molecular Characterization of Non-Endometrioid Endometrial Carcinoma.","authors":"Danqing Zhu, Keyi Shi, Dongxiao Hu, Wanrun Lin, Xiaofei Zhang, Feng Zhou, Yang Li","doi":"10.7150/jca.108685","DOIUrl":"https://doi.org/10.7150/jca.108685","url":null,"abstract":"<p><p><b>Objective:</b> Molecular classification has become an essential tool in endometrial carcinoma; however, its application in non-endometrioid carcinoma (NEEC), particularly rare histological subtypes, remains relatively unexplored. This study aims to investigate the potential utility of molecular classification in NEEC. <b>Methods</b>: A retrospective analysis was conducted on 167 NEEC cases diagnosed at the Women's Hospital of Zhejiang University from 2013 to 2020. The cases were categorized into four molecular subtypes: <i>POLE</i> ultra-mutated (<i>POLE</i>mut), mismatch repair-deficient (MMRd), p53-abnormal (p53abn), and no specific molecular profile (NSMP) molecular subgroups<i>.</i> Statistical significance was set at <i>P</i><0.05. <b>Results:</b> Among the cases, 13 (7.8%) patients were classified as <i>POLE</i>mut, 25 (15.0%) as MMRd, 84 (50.3%) as p53abn, and 45 (27.0%) as NSMP. Most <i>POLE</i>mut cases were at early stages (11/13, 84.6% at stages I-II), whereas p53abn cases were predominantly at advanced stages (32/49, 65.3% at stages III-IV). Additionally, p53abn was the most common subtype in serous carcinoma (41/45, 91.1%) and mixed adenocarcinoma (24/57, 42.1%). The 3-year recurrence-free survival (RFS) rates for <i>POLE</i>mut, MMRd, NSMP, and p53abn were 100.0%, 88.0%, 73.3%, and 71.4% , respectively. The 3-year overall survival (OS) rates were 100.0%, 88.0%, 82.2%, and 73.8%, respectively. Univariate analysis revealed significant associations of age ≥60 years (<i>P</i>=0.01), hypertension (<i>P</i>=0.03), FIGO stage (<i>P</i><0.001), lymphovascular space invasion (<i>P</i>=0.01), lymph node metastasis (<i>P</i><0.001), myometrial invasion (<i>P</i><0.001), and postoperative adjuvant therapy (<i>P</i>=0.01) with 3-year RFS. Multivariate analysis identified age ≥60 years (<i>P</i>=0.03), myometrial invasion (<i>P</i>=0.01), and FIGO stage (<i>P</i>=0.046) as independent risk factors for 3-year OS. <b>Conclusion:</b> Molecular classification is crucial for accurately predicting the prognosis of NEEC, enabling more tailored treatment approaches in clinical practice. Furthermore, patient age may have a significant influence on NEEC classification and progression.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 7","pages":"2312-2320"},"PeriodicalIF":3.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}