Journal of Cancer Research and Clinical Oncology最新文献

{"title":"Artificial neural networks as a prognostic tool using hyperspectral imaging on pretherapeutic histopathological specimens of esophageal adenocarcinoma.","authors":"Christel Teresa Trifone, Marianne Maktabi, Philipp Bischoff, Katrin Schierle, Stefan Niebisch, Yusef Moulla, Patrick Sven Plum, Boris Jansen-Winkeln, Ines Gockel, René Thieme","doi":"10.1007/s00432-025-06340-5","DOIUrl":"10.1007/s00432-025-06340-5","url":null,"abstract":"<p><strong>Purpose: </strong>The integration of artificial intelligence (AI) with hyperspectral imaging (HSI) offers a promising avenue for improving pre-therapeutic prognosis, a key factor in optimizing cancer treatment strategies. This study explores the potential of artificial neural networks (ANNs) to predict the effectiveness of preoperative chemo- or radiochemotherapy in esophageal adenocarcinoma (EAC), using HSI data derived from histopathological tissue samples.</p><p><strong>Methods: </strong>HSI data were obtained from pre-therapeutic histopathological samples of 21 patients with EAC. Following annotation and spectral extraction, the data underwent pre-processing steps including normalization, shuffling, and batch organization. Three artificial neural network (ANN) models-2D convolutional neural networks (2D-CNNs), 3D convolutional neural networks (3D-CNNs), and Hybrid-Spectral Networks (Hybrid-SN)-were trained to predict treatment response. Model performance was assessed using sensitivity, specificity, accuracy, and F1-score, offering insights into their clinical utility RESULTS: The 3D-CNN model achieved the highest accuracy (0.68 ± 0.09) and F1-score (0.66 ± 0.08), highlighting its strength in capturing both spatial and spectral information. The Hybrid-SN model demonstrated the highest sensitivity (0.79 ± 0.19), indicating strong performance in identifying responders to neoadjuvant therapy. In contrast, the 2D-CNN model achieved the highest specificity (0.73 ± 0.15), reflecting its effectiveness in correctly identifying non-responders.</p><p><strong>Conclusion: </strong>This study demonstrates the potential of combining HSI with ANNs to predict treatment response in EAC. Among the models evaluated, the 3D-CNN showed the most balanced performance, effectively leveraging spatial and spectral features, while the Hybrid-SN and 2D-CNN models excelled in sensitivity and specificity, respectively. These findings underline the feasibility of using AI-driven analysis of histopathological HSI data to support personalized treatment planning in EAC, paving the way for more accurate and tailored therapeutic strategies.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 10","pages":"274"},"PeriodicalIF":2.8,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12495013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225088","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":"Mapping the global clinical landscape of NK cell therapies for solid tumors: an analysis based on the ClinicalTrials.gov for the 2005-2024 period.","authors":"Wenjuan Wei, Ximeng Wu, Lizhi Wang, Jianing Zhang, Chan Zhang, Daqing Wang","doi":"10.1007/s00432-025-06329-0","DOIUrl":"10.1007/s00432-025-06329-0","url":null,"abstract":"","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 10","pages":"277"},"PeriodicalIF":2.8,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225261","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":"Evaluation of the gut microbiome and sex hormones in postmenopausal women with newly diagnosed hormone receptor-positive breast cancer versus healthy women: a prospective case-control study.","authors":"Maryann Kwa, Grant Hussey, Yelena Novik, Adrian A Franke, Angelina Volkova, Karina Flores, Martin J Blaser, James Speyer, Ruth Oratz, Marleen Meyers, Komal Jhaveri, Ezeddin Fadel, Adriana Heguy, Jonas Schluter, Kelly V Ruggles, Sylvia Adams","doi":"10.1007/s00432-025-06338-z","DOIUrl":"10.1007/s00432-025-06338-z","url":null,"abstract":"<p><strong>Purpose: </strong>The functional composition and diversity of the gut microbiome may affect breast cancer risk by modulation of systemic sex hormones. Gut bacteria with β-glucuronidase enzymatic activity may deconjugate estrogens, leading to increased estrogen reabsorption into the circulation thereby increasing breast cancer risk. We investigated the relationship between the gut bacterial microbiome and endogenous estrogens and related sex hormones in women with hormone receptor-positive breast cancer compared to healthy control women. The goal was to determine if the estrobolome (i.e., bacteria capable of modulating the body's circulated estrogen levels) was altered in those with breast cancer compared with controls.</p><p><strong>Methods: </strong>In this prospective case-control study, postmenopausal women (n = 46) with newly diagnosed stage I-III estrogen and/or progesterone receptor-positive breast cancer were compared with healthy postmenopausal female controls (n = 22). Bacterial composition of the gut microbiome was analyzed by 16S rRNA gene sequencing from fecal specimens. Plasma and urine sex hormones were quantified using high-performance liquid chromatography/mass spectrometry.</p><p><strong>Results: </strong>We found evidence that some β-glucuronidase positive bacteria were enriched in the breast cancer patients compared to healthy controls, whereas abundances of some β-glucuronidase negative bacteria were reduced. There was also a wide distribution of prevalence of β-glucuronidase positive taxa in both breast cancer subjects and healthy controls, as well as higher probability of breast cancer subjects having higher average β-glucuronidase levels. Significant differences were found in endogenous progesterone levels between the breast cancer patients and healthy controls.</p><p><strong>Conclusion: </strong>This pilot study showed differences in the gut microbiome and endogenous progesterone levels among postmenopausal women with hormone receptor-positive breast cancer compared with healthy controls. These interesting findings may have implications for breast cancer risk and prevention and warrant further exploration.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 10","pages":"275"},"PeriodicalIF":2.8,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225074","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":"tRF-34-86J8WPMN1E8Y2Q promotes the occurrence and development of gastric cancer by combining with LRAT.","authors":"Chunli Cao, Shengli Xu, Zhe Li","doi":"10.1007/s00432-025-06332-5","DOIUrl":"10.1007/s00432-025-06332-5","url":null,"abstract":"<p><strong>Background: </strong>A large number of studies have demonstrated that tRNA-derived fragments (tRFs) are implicated in the progression and nociception associated with various malignancies. However, the biological role of tRF-34-86J8WPMN1E8Y2Q (tRF-34) in cancer, particularly in gastric cancer (GC), remains elusive and warrants investigation. This study aimed to investigate the clinical and mechanistic significance of tRF-34 in GC pathogenesis and potential as novel biomarker for early detection.</p><p><strong>Methods: </strong>The quantitative expression levels of tRF-34 in GC cell lines, tissues, and plasma were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Subsequently, the functional impact of tRF-34 downregulation on GC progression was investigated using Cell Counting Kit-8 (CCK-8) assays to assess cell proliferation and transwell assays to evaluate migration and invasion. Downstream target genes of tRF-34 were identified through database analysis and validated using RNA Binding Protein Immunoprecipitation (RIP) experiments.</p><p><strong>Results: </strong>tRF-34 exhibits elevated expression levels in GC tissues cells and preoperative (1 day) plasma compared with normal counterparts and postoperative (10 day) plasma. Also, it was associated with neural and vascular invasion in patients with GC. Moreover, tRF-34 downregulation impedes the proliferative, migratory, and invasive capacities of GC cells. Mechanistically, RIP and bioinformatic analyses demonstrated that tRF-34 directly bound to lecithin retinol acyltransferase (LRAT), and this interaction promoted the progression of GC.</p><p><strong>Conclusion: </strong>tRF-34 has high expression specificity in GC and the potential to be a biomarker for early detection. Also, tRF-34 directly binds to LRAT, facilitating GC progression.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 10","pages":"276"},"PeriodicalIF":2.8,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225177","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":"EYA1 promotes tumor angiogenesis in colorectal cancer by activating HIF-1β through LSD2-mediated H3K4me2 demethylation.","authors":"Shaoxin Cai, Jiansheng Wu, Naisen Wang, Chengchuan Zheng, Jianglin Su, Changqing Zeng, Jinsi Wang","doi":"10.1007/s00432-025-06270-2","DOIUrl":"10.1007/s00432-025-06270-2","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is one of the most common cancers worldwide, with tumor angiogenesis playing a crucial role in its progression. The Drosophila Eyes Absent Homologue 1(Eya1) has been implicated in various cancers, but its mechanism in CRC angiogenesis remains unclear. This study explores the mechanism by which Eya1 regulates angiogenesis in CRC by activating HIF-1β through Lysine-specific demethylases 2 (LSD2).</p><p><strong>Methods: </strong>CRC tissues and cell lines were analyzed to assess Eya1 and LSD2 using qPCR and Western blot. VEGFA expression and endothelial cell proliferation were measured using ELISA and tube formation assays. Co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP) assays were used to investigate protein interactions and histone modifications.</p><p><strong>Results: </strong>We found that Eya1 and LSD2 were significantly upregulated in CRC tissues and cell lines. Eya1 overexpression increased VEGFA expression and promoted endothelial cell proliferation and tube formation, and the effects were abolished upon silencing LSD2 or HIF-1β. Additionally, Eya1 was shown to interact with Dach1, a co-stimulatory factor, to regulate LSD2 expression and its activity in promoting HIF-1β-mediated angiogenesis.</p><p><strong>Conclusion: </strong>This study demonstrates that Eya1 promotes CRC angiogenesis through the LSD2/HIF-1β/VEGF pathway. These findings identify a novel mechanism of angiogenesis regulation in CRC, suggesting that targeting the Eya1-LSD2-HIF-1β axis may provide new therapeutic strategies for CRC treatment.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 10","pages":"278"},"PeriodicalIF":2.8,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12495011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225211","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":"Pellino ubiquitin ligases: double-edged swords in hematologic malignancies-from oncogenic stabilizers to therapeutic vulnerabilities.","authors":"Mingfeng Yang, Ya Li, Jianhong Wang","doi":"10.1007/s00432-025-06331-6","DOIUrl":"10.1007/s00432-025-06331-6","url":null,"abstract":"<p><p>The Pellino protein family is an evolutionarily conserved group of E3 ubiquitin ligases comprising Pellino1, Pellino2, and Pellino3. This family plays a central role in modulating inflammatory responses and immune signaling pathways through substrate ubiquitination. Recent studies have revealed that the Pellino family performs a unique dual regulatory function within the immune microenvironment of hematological malignancies. On the one hand, it contributes to tumor progression by promoting an immunosuppressive environment, such as enhancing the function of myeloid-derived suppressor cells (MDSCs) and increasing tumor cell drug resistance. On the other hand, it exhibits tumor-suppressive properties by activating antitumor immune responses, including the regulation of CD8⁺T-cell effector functions and the enhancement of NK cell cytotoxicity. The underlying molecular mechanisms involve bidirectional regulation of multiple signaling pathways, such as the Toll-like receptor, IL-1R, T-cell receptor, and nonclassical nuclear factor kappa B(NF-κB) pathways, thereby dynamically balancing the immune status within the tumor microenvironment. Clinical studies have demonstrated that the expression levels of Pellino family members are closely associated with the diagnosis, classification, and prognosis of hematological tumors, indicating their potential as biomarkers. Moreover, targeted intervention strategies based on their E3 ubiquitin ligase activity may offer novel approaches to increase the efficacy of immunotherapies. This review summarizes the structural and functional characteristics of the Pellino protein family, its dual regulatory mechanisms in the immune microenvironment of hematological tumors, and recent advances in clinical translation, aiming to provide a theoretical foundation for further understanding its biological roles and promoting targeted therapeutic research.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 10","pages":"273"},"PeriodicalIF":2.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12480165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191660","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":"Retrospective analysis of asparaginase-associated pancreatitis in pediatric acute lymphoblastic leukemia: focus on rechallenge with pegaspargase.","authors":"Chenhong Jia, Qian Li, Xiaoying Zhai, Meijie Quan, Bing Bai, Xiangyu Ding","doi":"10.1007/s00432-025-06333-4","DOIUrl":"10.1007/s00432-025-06333-4","url":null,"abstract":"<p><strong>Purpose: </strong>The incidence of asparaginase-associated pancreatitis (AAP) in children with acute lymphoblastic leukemia (ALL) may lead to treatment delays and insufficient drug exposure, thereby increasing the risk of ALL relapse. We aimed to understand the clinical characteristics and management of AAP, which are crucial for improving treatment outcomes in children with ALL.</p><p><strong>Methods: </strong>We retrospectively analyzed the medical records of children diagnosed with AAP and admitted to Hebei Children's Hospital between April 2019 and July 2024. We analyzed the clinical characteristics and management strategies of AAP in children with ALL, with a particular focus on the treatment strategies and AAP recurrence in children who were rechallenged with pegaspargase (PEG-ASP).</p><p><strong>Results: </strong>Among 474 patients treated for ALL, 32 were diagnosed with AAP (incidence rate, 6.8%). Of these 32 cases, mild pancreatitis accounted for 50.0% (16/32), moderately severe pancreatitis for 43.8% (14/32), and severe pancreatitis for 6.3% (2/32). AAP occurred most frequently during the induction and early intensive therapy phases. The median time to onset of AAP was 10.5 (1-26) days, and the median number of PEG-ASP doses administered was three (range 1-11). Notably, 53.1% (17/32) patients were rechallenged with PEG-ASP, of whom seven experienced AAP recurrence, including one with three episodes. Despite these statuses, all patients either recovered or showed improvement in their disease status, and no mortality was reported.</p><p><strong>Conclusion: </strong>AAP in children with ALL can be effectively managed through early detection and appropriate treatment. Rechallenge with PEG-ASP should be individualized to balance the risk of recurrence against the benefits of continued therapy.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 10","pages":"272"},"PeriodicalIF":2.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12480329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191652","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":"Real-world evidence on the additional cancer risk reduction of ezetimibe: a 10-year nationwide retrospective cohort study emulating a target trial.","authors":"Yohwan Lim, Eunji Kim, Eunjung Hwang, Koanhoi Kim, Yonghae Son, Sang Yeoup Lee, Young Hye Cho, Eun-Ju Park, Youngin Lee, Sae Rom Lee, Jung-In Choi, Han-Sol Jeong, Su-Jung Park, Soo Min Son, Ryuk Jun Kwon","doi":"10.1007/s00432-025-06339-y","DOIUrl":"10.1007/s00432-025-06339-y","url":null,"abstract":"","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 10","pages":"271"},"PeriodicalIF":2.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185872","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":"Management of hepatotoxicity associated with CDK4/6 inhibitors and rechallenge strategies in metastatic hormone-positive, HER2-NEGATIVE BREAST CANCER.","authors":"Nurullah İlhan, Süleyman Baş, Onur Alkan, Akif Doğan, Nargiz Majidova, Mustafa Alperen Tunç, Engin Erdemoğlu, Buğra Öztosun, İlker Nihat Ökten, Mahmut Gümüş","doi":"10.1007/s00432-025-06336-1","DOIUrl":"10.1007/s00432-025-06336-1","url":null,"abstract":"<p><strong>Background: </strong>Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy have significantly improved clinical outcomes in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR + /HER2-) metastatic breast cancer. Hepatotoxicity is a known class-related adverse event that may interrupt or modify treatment. However, real-world evidence on its incidence, risk factors, and management strategies-particularly rechallenge approaches-remains limited. This study aimed to evaluate the frequency and clinical characteristics of CDK4/6 inhibitor-associated hepatotoxicity, to identify risk factors, and to assess the outcomes and safety of rechallenge following liver injury.</p><p><strong>Methods: </strong>This retrospective multicenter study included 544 patients with HR+ /HER2- metastatic breast cancer who were treated with ribociclib or palbociclib between January 2017 and July 2024 in oncology centers across Turkey. Abemaciclib was not included due to reimbursement limitations during the study period. Patient characteristics, comorbidities, concomitant medications, and herbal or dietary supplement use were recorded. Liver function tests and viral hepatitis serologies were analyzed. Hepatotoxicity was graded using the Common Terminology Criteria for Adverse Events (CTCAE v5.0), and causality was assessed with the Roussel Uclaf Causality Assessment Method (RUCAM). Management strategies-including dose interruption, dose reduction, switching to another CDK4/6 inhibitor, and outcomes of rechallenge were evaluated.</p><p><strong>Results: </strong>Hepatotoxicity occurred in 10.5% of patients, most commonly in a hepatocellular pattern. Ribociclib was the most frequently used agent. Younger age, herbal supplement use, and hepatitis B carrier status were significantly associated with increased risk of hepatotoxicity. All hepatotoxic events were managed conservatively. None of the patients developed acute liver failure or required invasive evaluation. Dose reduction or switching to the alternate agent was attempted in most patients after enzyme normalization and was successful in the majority, with no recurrence of severe hepatotoxicity.</p><p><strong>Conclusion: </strong>CDK4/6 inhibitor-related hepatotoxicity is manageable with careful monitoring and individualized strategies. Timely dose interruption, switching agents, or cautious rechallenge allowed most patients to resume therapy safely. These findings support the continued use of CDK4/6 inhibitors in eligible patients, even after hepatotoxicity events.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 10","pages":"270"},"PeriodicalIF":2.8,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145175455","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":"Casein kinase 1 family member CSNK1E can regulate proliferation and migration in hepatocellular carcinoma.","authors":"Jie Zhou, Yu-Hui Wang, Yong-Le Li, Xiao-Mei Xie, Zhou Jiang, Xin Zhuo, Xu-Dong Shan, Shu-Tin Cheng, Li-He Jiang","doi":"10.1007/s00432-025-06321-8","DOIUrl":"10.1007/s00432-025-06321-8","url":null,"abstract":"<p><strong>Purpose: </strong>Some studies have shown that circadian rhythms are associated with the development and progression of hepatocellular carcinoma (HCC). In this study, we aimed to elucidate the characterization, prognostic significance and targeting value of circadian rhythm gene CSNK1E in HCC.</p><p><strong>Methods: </strong>In this study, relevant datasets were downloaded from TCGA and GEO databases and analyzed for differences respectively. The key modules of the prognosis-related gene set were identified using WGCNA, and the intersection of the key module genes with 48 circadian rhythm genes was taken and analyzed in single-cell data. The identification of key circadian rhythm genes in HCC aimed to analyze the expression, prognostic significance, and clinically relevant features of CSNK1E in cancer. The expression characteristics of CSNK1E were further examined by immunohistochemistry, western blotting (WB), and Real-time quantitative PCR (qRT-PCR). The effects of CSNK1E on the phenotypes of HCC cells were evaluated using Cell Counting Kit-8 (CCK8), flow cytometry, Transwell assay and Wound healing assay. Furthermore, transcriptomic analysis identified HIPPO signaling pathway as a potential pathway involving CSNK1E. The functional role of CSNK1E in HIPPO signaling was subsequently validated through western blotting (WB) and quantitative real-time PCR (qRT-PCR) assays.</p><p><strong>Results: </strong>We constructed a prognostic model of key circadian rhythm-related genes (CSNK1E, CSNK1D, CSNK2A1, and CSNK2B) to predict the prognosis and survival of HCC patients. The high-risk group had a worse prognosis compared to the low-risk group, which was confirmed by ROC curves and survival curves. CSNK1E expression levels were significantly associated with clinicopathological features and identified as a robust and independent prognostic biomarker in HCC. Higher CSNK1E expression levels were associated with poorer overall survival in various clinical subgroups. The cell experiment showed that CSNK1E knockdown suppressed cell proliferation, migration, and invasion while promoting apoptosis; its overexpression produced opposite effects. Moreover, CSNK1E may mediate HCC cell proliferation through Hippo signaling pathway.</p><p><strong>Conclusions: </strong>The finding that the circadian gene CSNK1E contributes to HCC progression through activation of HIPPO signaling pathway suggests that it may be a promising therapeutic target for HCC.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 10","pages":"269"},"PeriodicalIF":2.8,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145175443","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}