Anticancer research最新文献

{"title":"Thorough Lymphadenectomy Impairs Immunotherapy Outcomes for Postoperative Intrathoracic Recurrence of Non-small Cell Lung Cancer.","authors":"Masaya Aoki, G O Kamimura, Yusei Tsuneyoshi, Shoichiro Morizono, Takuya Tokunaga, Aya Harada-Takeda, Koki Maeda, Toshiyuki Nagata, Kota Kariatsumari, Kazuhiro Ueda","doi":"10.21873/anticanres.17755","DOIUrl":"https://doi.org/10.21873/anticanres.17755","url":null,"abstract":"<p><strong>Background/aim: </strong>Immune checkpoint inhibitors (ICIs) have emerged as a standard treatment for recurrent non-small cell lung cancer (NSCLC). However, the factors predicting their efficacy in postoperative recurrence remain unclear.</p><p><strong>Patients and methods: </strong>We retrospectively analyzed 30 patients who underwent complete surgical resection of NSCLC and subsequently received ICI monotherapy for recurrence. Clinicopathological factors, including the programmed death ligand 1 (PD-L1) expression and number of dissected lymph nodes (DLNs), were evaluated for their association with the treatment response and prognosis.</p><p><strong>Results: </strong>The high expression of PD-L1 (≥50%) in surgical specimens was significantly associated with higher response rates, prolonged progression-free survival (PFS), and overall survival (OS) after the initiation of ICI therapy. In contrast, patients with ≥15 DLNs had a significantly shorter PFS than those with <15 DLNs, particularly in patients without extrathoracic recurrence. A multivariate analysis identified the expression of PD-L1, the number of DLNs, and the presence of extrathoracic metastasis as independent prognostic factors for ICI-PFS.</p><p><strong>Conclusion: </strong>Extensive lymphadenectomy may worsen the prognostic outcomes of ICI monotherapy, possibly by impairing tumor-draining lymph node-mediated immunity. These findings highlight the importance of lymphatic preservation and support the clinical rationale for neoadjuvant ICI therapy for resectable NSCLC.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 9","pages":"3971-3981"},"PeriodicalIF":1.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multidisciplinary Therapy of Uterine Ewing's Sarcoma With the Preservation of Uterus and Ovarian Function by Laparoscopy: A Case Report and Literature Review.","authors":"Shigenori Furukawa, Shu Soeda, Hisahito Endo, Yuki Yoshimoto, Asami Kato, Chikako Okabe, Hideki Miura, Tetsu Sato, Norihito Kamo, Yuta Endo, Hisashi Yamaguchi, Yoshiaki Takagawa, Yoshihiro Ohara, Hideki Sano, Yuichiro Kiko, Hiroshi Hojo, Yuko Hashimoto, Keiya Fujimori","doi":"10.21873/anticanres.17760","DOIUrl":"https://doi.org/10.21873/anticanres.17760","url":null,"abstract":"<p><strong>Background/aim: </strong>Primary uterine Ewing's Sarcoma is an extremely rare and aggressive tumor. Due to its rarity, there is no established standard treatment, and most cases involve radical surgery, often compromising fertility and ovarian function. Recent advances in multimodal therapy have introduced fertility-preserving approaches for young patients.</p><p><strong>Case report: </strong>An 18-year-old woman visited our hospital for a detailed examination of a 10 cm-sized uterine tumor initially diagnosed as a leiomyoma by MRI. A GnRH agonist was administered to treat presumed myoma and associated anemia. Despite the administration of three cycles of the GnRH agonist, the patient's anemia did not improve. The size of the tumor was not reduced, and the inner structure of the tumor became irregular. A tumorectomy was performed and the uterus was repaired. Histological examination, including immunohistochemical staining, suggested Ewing's Sarcoma based on hematoxylin-eosin findings and strong CD99 positivity. Fluorescence in situ hybridization confirmed ESWR1 gene rearrangement in the tumor cells, leading to a definitive diagnosis of Ewing's Sarcoma. Since PET-CT showed pelvic and para-aortic lymph metastasis after laparotomy, VDC-IE chemotherapy was performed after oocyte cryopreservation. The multiple swellings of the lymph nodes were improved. To enhance curative potential, proton therapy was administered to the whole pelvis and para-aortic lymph nodes. To preserve ovarian function, a laparoscopic ovarian transposition was performed before proton therapy. Her right ovary was mobilized to the peritoneum at the level of the upper lobe of the right kidney <i>via</i> a retroperitoneal tunnel. 54-Gy proton therapy was performed, and complete response was obtained.</p><p><strong>Conclusion: </strong>This case of primary uterine Ewing's Sarcoma was treated with multimodal therapy, achieving curative outcome while preserving ovarian function and fertility through laparoscopic ovarian transposition.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 9","pages":"4027-4035"},"PeriodicalIF":1.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ifosfamide-induced Catatonia - A Rare Presentation and Review of Ifosfamide-induced Central Nervous System Toxicity Along With Therapeutic Approaches.","authors":"Stanley Lyndon","doi":"10.21873/anticanres.17694","DOIUrl":"10.21873/anticanres.17694","url":null,"abstract":"<p><strong>Background/aim: </strong>Ifosfamide is a well-known chemotherapeutic agent used to treat various cancer types but is associated with central nervous system toxicity, termed ifosfamide-induced encephalopathy (IIE). Rarely, this toxicity manifests as catatonia.</p><p><strong>Case report: </strong>We present the case of a 61-year-old woman with diffuse large B-cell lymphoma who developed profound catatonia after ifosfamide infusion. Her symptoms resolved completely following a single intravenous dose of lorazepam.</p><p><strong>Conclusion: </strong>This case underscores the importance of recognizing catatonia as a manifestation of IIE and supports the use of lorazepam as both a diagnostic and therapeutic intervention.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 8","pages":"3341-3346"},"PeriodicalIF":1.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Comprehensive Genomic Profiling Testing \"Ion Torrent Genexus Sequencer\" With FoundationOne.","authors":"Kenji Fujiyoshi, Rie Sugihara, Naoki Miyamoto, Yoriko Watanabe, Tomoya Sudo, Sanae Numata, Jun Akiba, Hideyuki Abe, Yuka Ichinose, Kenji Inoue, Shuichi Ozono, Takeharu Ono, Kentaro Orioka, Masaki Kashihara, Ryousuke Kajiwara, Hiroyuki Kawano, Akihiko Kawahara, Ryuta Takase, Uhi Toh, Kazuaki Hashimoto, Toru Hisaka, Shingo Hirai, Masahiro Mitsuoka, Daiki Miyazaki, Fumi Yoshitomi, Ken Yamamoto, Hirohito Umeno, Masahisa Nomura, Yoshiki Naito","doi":"10.21873/anticanres.17709","DOIUrl":"https://doi.org/10.21873/anticanres.17709","url":null,"abstract":"<p><strong>Background/aim: </strong>Comprehensive genomic profiling (CGP) with tissue- and blood-based next-generation sequencing (NGS) is integral to the delivery of personalized medicine for targeted cancer therapy. This study aimed to evaluate the variant concordance for somatic variants using two clinical NGS systems for conducting both tissue- and blood-based analyses: Genexus-OCA v3 (OCA) <i>vs.</i> FoundationOne CDx (F1) for tissues and Genexus OPA (OPA) <i>vs.</i> FoundationOne CDx Liquid (F1L) for blood.</p><p><strong>Patients and methods: </strong>The concordance of genomic alterations between the two NGS analyses was compared in six patients with breast, head, and neck cancers using tissue and circulating tumor DNA biopsies.</p><p><strong>Results: </strong>A total of 130 genes were common between F1 and OCA, and 41 between F1L and OPA. When comparing FoundationOne to Genexus for common genes, the sensitivity and specificity of OCA and OPA were 55% and 99%, respectively. Nine single-nucleotide variants (SNVs), one copy number alteration (CNA), and one fusion were detected by both Genexus and FoundationOne. However, one SNV (<i>MAP2K1</i> F53V), two CNAs (<i>AKT3</i> and <i>MYC</i>), and one fusion (<i>ESR-CCDC170</i>) were detected only in Genexus, whereas two SNVs (<i>TP53</i> Q331* and <i>KRAS</i> G12V) were detected only in FoundationOne.</p><p><strong>Conclusion: </strong>The two cancer genome panels were equivalent but not perfect in terms of the detection of variants using tissue and blood, indicating that different assays and analytical methods may have influenced the results. When performing CGPs, it is important to consider the characteristics of each NGS-based CGP test and the genetic variants associated with each disease.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 8","pages":"3479-3486"},"PeriodicalIF":1.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Sulfonamide Group Modification on Celecoxib: Molecular Features of Matrix Metalloproteinase Interactive UTX-121 Derivative.","authors":"Kazuto Ohkura, Atsushi Tabata, Yoshihiro Uto","doi":"10.21873/anticanres.17706","DOIUrl":"https://doi.org/10.21873/anticanres.17706","url":null,"abstract":"<p><strong>Background/aim: </strong>Matrix metalloproteinases (MMPs) are important for extracellular matrix (ECM) degradation with MMP inhibition possibly leading to new antitumor therapies. To examine this possibility, UTX-121, in which the celecoxib sulfonamide was replaced with a methyl ester, was designed to examine the influence of UTX-121 derivatives on MMPs.</p><p><strong>Materials and methods: </strong>HT-1080 cells were incubated with UTX-121 derivatives over 48 h, and antitumor activities (IC₅₀) were examined using WST-8 assay. The inhibitory effect of UTX-121 derivatives on MMPs in HT-1080 cells was examined using gelatin zymography. Conformational analyses of UTX-121 derivatives were performed using CAChe-Conflex. The interaction of UTX-121 derivatives with MMPs was analyzed using Molegro Virtual Docker.</p><p><strong>Results: </strong>UTX-121 derivative a2 exhibited enhanced antitumor activity compared to UTX-121. Additionally, derivative a2 demonstrated stronger inhibitory effects on MMP-2, as indicated by reduced band intensity in gelatin zymography, compared to UTX-121. Molecular docking simulations revealed that a2 formed a hydrogen bond with the Tyr³⁶⁶ residue of MMP-2 <i>via</i> the oxygen atom of its methoxy group, supporting its enhanced interaction and inhibitory potency.</p><p><strong>Conclusion: </strong>UTX-121 derivative a2 showed improved MMP-2 inhibitory activity through specific hydrogen bonding interactions and holds promise as a lead compound for the development of novel MMP-2-targeted anticancer agents.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 8","pages":"3451-3457"},"PeriodicalIF":1.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silencing of Acyl-CoA Thioesterase 7 Inhibits Proliferation and Metastatic Potential in Colorectal Cancer Cells.","authors":"Sumi Lee, Jae Woong Koh, Jung-Hee Lee, Seon-Joo Park","doi":"10.21873/anticanres.17692","DOIUrl":"https://doi.org/10.21873/anticanres.17692","url":null,"abstract":"<p><strong>Background/aim: </strong>Acyl-CoA thioesterase 7 (<i>ACOT7</i>) has emerged as a candidate gene implicated in various malignancies. However, its functional relevance in colorectal cancer (CRC) remains poorly understood.</p><p><strong>Materials and methods: </strong>To investigate the role of ACOT7 in CRC, we examined its expression in normal colon epithelial cells and a panel of CRC cell lines using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Functional analyses were performed following siRNA-mediated knockdown of <i>ACOT7</i> to assess changes in cell proliferation, clonogenicity, cell cycle distribution, apoptosis, migration, and invasion using MTT, colony formation, flow cytometry, and Transwell-based assays.</p><p><strong>Results: </strong>ACOT7 was markedly over-expressed at both the mRNA and protein levels in CRC cells compared to normal epithelial cells. Silencing <i>ACOT7</i> substantially reduced cell proliferation and clonogenic potential. Flow cytometric analysis indicated cell cycle arrest and an increase in the sub-G₀/G₁ population, indicative of apoptosis in ACOT7-depleted cells. Furthermore, suppression of <i>ACOT7</i> substantially impaired both cell migration and invasion, suggesting its key role in metastatic progression.</p><p><strong>Conclusion: </strong>These findings highlight <i>ACOT7</i> as a critical regulator of the proliferation, survival, and metastatic potential of CRC cells and support its candidacy as a potential therapeutic target for colorectal malignancies.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 8","pages":"3315-3325"},"PeriodicalIF":1.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nucleoporin 188 as a Predictive Biomarker of Poor Prognosis in Muscle-invasive Bladder Cancer.","authors":"Mingxing Zheng, Jianming Lu, Wenshi Yu, Yaxian Li, Yonglu Wu, Yuhui Yao, Huizhen Tian, Liangliang Huang, L E Zhang, Junhong Deng","doi":"10.21873/anticanres.17686","DOIUrl":"https://doi.org/10.21873/anticanres.17686","url":null,"abstract":"<p><strong>Background/aim: </strong>Muscle-invasive bladder cancer (MIBC) represents a significant clinical challenge due to its aggressive nature. Identifying reliable biomarkers to predict prognosis is critical for improving patient outcomes. Nucleoporin 188 (NUP188), a component of nuclear pore complexes, has emerged as a potential candidate, yet its role in MIBC remains underexplored.</p><p><strong>Materials and methods: </strong>This study analyzed NUP188 expression across multicenter MIBC cohorts from TCGA, GSE48075, and GSE169455, as well as the immunotherapy cohorts, using Kaplan-Meier survival analysis and Cox regression to assess prognostic significance. <i>In vitro</i> assays in 5637 and UM-UC-3 cell lines evaluated the effects of NUP188 knockdown on proliferation and migration. Pathway enrichment and Gene Set Variation Analysis (GSVA) were employed to investigate mechanistic associations.</p><p><strong>Results: </strong>Elevated NUP188 expression was consistently associated with poor overall survival, progression-free interval, and disease-specific survival across MIBC cohorts, establishing it as an independent adverse prognostic factor. In the immunotherapy cohorts, high NUP188 levels correlated with reduced survival and immunotherapy non-responsiveness. <i>In vitro</i>, NUP188 silencing significantly suppressed proliferation and migration of MIBC cell lines. In addition, NUP188 was linked to metabolic reprogramming, particularly lipid metabolism, and exhibited distinct mutational profiles.</p><p><strong>Conclusion: </strong>NUP188 emerges as a novel biomarker predictive of poor prognosis in MIBC. Its influence on cellular proliferation, migration, and metabolic pathways underscores its potential as a therapeutic target.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 8","pages":"3245-3261"},"PeriodicalIF":1.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-6 Secreted from Cancer-associated Fibroblast Inhibits Cancer Growth in Biliary Tract Cancer.","authors":"Naoki Tani, Shimpei Eguchi, Kenjiro Kimura, Ryota Tanaka, Masahiko Kinoshita, Kohei Nishio, Hiroji Shinkawa, G O Ohira, Shogo Tanaka, Masakazu Yashiro, Takeaki Ishizawa","doi":"10.21873/anticanres.17681","DOIUrl":"https://doi.org/10.21873/anticanres.17681","url":null,"abstract":"<p><strong>Background/aim: </strong>Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment and can either promote or suppress tumor growth. This study aimed to identify CAFs that inhibit proliferation in biliary tract cancer (BTC) cell lines and explore the underlying mechanisms.</p><p><strong>Materials and methods: </strong>Three BTC cell lines and one pancreatic cancer cell line were treated with conditioned media (CM) from CAFs isolated from BTC specimens. Cell proliferation was assessed, and cytokine profiles in CM were analyzed using protein arrays. Expression of interleukin-6 (IL-6) pathway proteins was examined via western blot and immunohistochemistry (IHC) in BTC tissues. Survival outcomes were analyzed using Kaplan-Meier curves.</p><p><strong>Results: </strong>Some BTC-derived CAFs suppressed cancer cell growth. IL-6 was identified in the CM as a key inhibitory cytokine. IL-6 treatment significantly reduced BTC cell proliferation, accompanied by increased suppressor of cytokine signaling 3 (SOCS3) and decreased activator of transcription 3 (STAT3) expression. In BTC patient tissues, stromal IL-6 expression correlated with improved relapse-free survival (RFS; 60.8 <i>vs.</i> 18.5 months, <i>p</i>=0.008) and overall survival (OS; 61.6 <i>vs.</i> 33.9 months, <i>p</i>=0.05). Patients with positive expression of IL-6 receptor subunits CD130 and CD126, as well as SOCS3, had significantly longer RFS and/or OS compared to negative cases. For CD130, median RFS and OS were 60.8 <i>vs.</i> 17.4 months (<i>p</i>=0.02) and 60.7 <i>vs.</i> 34.6 months (<i>p</i>=0.05), respectively. For SOCS3, RFS and OS were 60.8 <i>vs.</i> 21.1 months (<i>p</i>=0.05) and 51.6 <i>vs.</i> 34.8 months (<i>p</i>=0.04). CD126 positivity was associated with longer RFS (60.8 <i>vs.</i> 21.1 months, <i>p</i>=0.04), but OS did not differ significantly.</p><p><strong>Conclusion: </strong>A subset of CAFs in BTC has tumor-suppressive activity mediated by IL-6, which inhibits cancer cell proliferation <i>via</i> the SOCS3/STAT3 pathway and correlates with better clinical outcomes.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 8","pages":"3183-3196"},"PeriodicalIF":1.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preface.","authors":"Toshiyuki Tsunoda, Toyofumi Hirakawa","doi":"10.21873/anticanres.17719","DOIUrl":"https://doi.org/10.21873/anticanres.17719","url":null,"abstract":"","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 8","pages":"3575"},"PeriodicalIF":1.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deletion of the <i>POLR2J4</i> Gene in Breast Cancer Cells Promotes Bone Metastatic Tumor Growth.","authors":"Seong-Ho Park, DA Hyun Yoon, Jungwoo Kim, Serk In Park, Junho K Hur, Sung Bae Park","doi":"10.21873/anticanres.17687","DOIUrl":"https://doi.org/10.21873/anticanres.17687","url":null,"abstract":"<p><strong>Background/aim: </strong>Multiple genetic alterations accumulate during the progression of bone metastasis. Previously, we identified <i>POLR2J4</i> as a causal gene associated with breast cancer bone metastasis. This study aimed to investigate the roles of <i>POLR2J4</i> in breast cancer bone metastasis in a murine model.</p><p><strong>Materials and methods: </strong>We engineered and knocked out the <i>POLR2J4</i> gene in luciferase-labeled MDA-MB-231 breast cancer cells using the CRISPR-spCas9 system. Parental or <i>POLR2J4</i>-knockout cells were injected into the systemic circulation of female nude mice. Development and growth of bone metastatic lesions were monitored by weekly bioluminescence imaging. After four weeks, mice were sacrificed for histological analysis of their bone lesions. In addition, transcriptomics analysis using RNA sequencing was performed in <i>POLR2J4</i> knockout <i>vs.</i> parental cells to investigate gene expression changes. POLR2J4 knockout was confirmed by target sequencing and quantitative RT-PCR.</p><p><strong>Results: </strong>The <i>POLR2J4</i> knockout group had significantly increased incidence of bone metastasis, compared with the control group (<i>p</i><0.01, Fisher's exact test, <i>n</i>=28/group). However, no statistical significance was observed in the metastatic tumor size measured by bioluminescence signal intensities. Bioluminescence-positive metastatic lesions were confirmed for tumor cells microscopically. Among the genes differentially expressed between the knockout and control cells, CD74 was significantly up-regulated.</p><p><strong>Conclusion: </strong><i>POLR2J4</i> is a negative regulator of breast cancer bone metastasis, and CD74 up-regulation in the <i>POLR2J4</i> knockout cells contributes to the pro-metastatic phenotype. Overall, our data warrant further investigation on the role of <i>POLR2J4</i> as a causal gene of breast cancer bone metastasis.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 8","pages":"3263-3273"},"PeriodicalIF":1.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}