Cancer Science最新文献

{"title":"Gastric Signet Ring Cell Carcinoma in a Helicobacter pylori-Positive 10-Year-Old Boy: A Case Report and Literature Review","authors":"Xiaoxuan Li,&nbsp;Xinchi Luan,&nbsp;Wenjuan Yu,&nbsp;Shibo Wang,&nbsp;Xiangxue Li,&nbsp;Lihua Zhang,&nbsp;Siyi Zhang,&nbsp;Jialin Song,&nbsp;Jing Guo,&nbsp;Shasha Wang,&nbsp;Wensheng Qiu,&nbsp;Jing Lv","doi":"10.1111/cas.70112","DOIUrl":"10.1111/cas.70112","url":null,"abstract":"<p>Gastric cancer is rare in pediatric populations, with gastric signet ring cell carcinoma (GSRCC) being an exceptionally infrequent subtype. We report a case of GSRCC in a 10-year-old Chinese boy with no family history of cancer. The diagnosis was established via gastroscopy, endoscopic ultrasound, and imaging examinations. Early detection allowed a successful distal gastrectomy with D2 lymph node dissection. Postoperative whole-exome sequencing (WES) revealed no clinically significant mutations but identified some somatic alterations. Notably, gastric biopsy pathology demonstrated strong positivity for <i>Helicobacter pylori</i> (<i>H. pylori</i>) infection. Additionally, we comprehensively reviewed the existing pediatric GSRCC cases, suggesting the potential role of <i>H. pylori</i> infection in the pathogenesis of pediatric gastric cancer.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 8","pages":"2064-2074"},"PeriodicalIF":4.3,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PC4 Potentially Predicts Chemoradiation-Induced Antitumor Immunity in Esophageal Squamous Cell Carcinoma","authors":"Jieyong Tian,&nbsp;Xiaoying Wei,&nbsp;Huiquan Liu,&nbsp;Qingsong Pang,&nbsp;Dong Qian,&nbsp;Haiming Dai","doi":"10.1111/cas.70117","DOIUrl":"10.1111/cas.70117","url":null,"abstract":"<p>Chemoradiotherapy (CRT) induces an antitumor immune response in esophageal squamous cell carcinoma (ESCC), and thereby has enormous potential by itself and in combination with immune checkpoint inhibitors (ICI). Our previous studies indicated that human positive cofactor 4 (PC4) was an independent predictor of poor survival in patients with ESCC or lung cancer who were treated with definitive chemoradiation, with a mechanism involving the enhancement of nonhomologous end joining (NHEJ)-mediated DNA repair. Due to the important role of double-strand DNA (dsDNA) in the antitumor immune response, the present study aims to investigate PC4 as a predictor of pathological response and antitumor immune response in ESCC patients who underwent neoadjuvant CRT. In ESCC, low PC4 expression levels have significant power to predict pCR. In particular, pCR is 61.2% in patients with low PC4 expression, but only 23.4% in patients with high PC4. Both disease-free survival (DFS) and overall survival (OS) are significantly longer for patients with low PC4 than for those with high PC4. In agreement with our previous finding that PC4 participates in NHEJ-mediated DNA repair, our further analysis indicates that the expression of PC4 is not only significantly negatively correlated with cyto-free dsDNA in postoperative specimens, but also with tumor-infiltrating CD8⁺T lymphocytes (CD8⁺TILs) and GZMB⁺CD8⁺TILs, suggesting a possible mechanism that high PC4 negatively regulates the antitumor response and therefore results in poor prognosis. Together, our findings demonstrate that low expression of PC4 is a potential biomarker for predicting the antitumor immune response to chemoradiation in patients with operable locally advanced ESCC.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 9","pages":"2362-2373"},"PeriodicalIF":4.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dauricine Overcomes Osimertinib Resistance in Lung Cancer by Inducing Ferroptosis via Stabilizing SAT1","authors":"Biying Men,&nbsp;Zhijie Chen,&nbsp;Haotian Ge,&nbsp;Zhuoying Yang,&nbsp;Liang Yun,&nbsp;Jianjun Jiang,&nbsp;Meijuan Dian,&nbsp;Yujing He,&nbsp;Zehao Zhou,&nbsp;Ruihao Zhang,&nbsp;Tianbao Yan,&nbsp;Zichao Li,&nbsp;Yingxin Zhang,&nbsp;Yongjie He,&nbsp;Junming He,&nbsp;Xuguang Rao,&nbsp;Shuan Rao","doi":"10.1111/cas.70113","DOIUrl":"10.1111/cas.70113","url":null,"abstract":"<p>Osimertinib is a third-generation EGFR tyrosine kinase inhibitor (TKI) widely used to treat advanced nonsmall cell lung cancer (NSCLC) with EGFR mutations. However, resistance to osimertinib frequently develops, limiting its long-term effectiveness. In this study, we used osimertinib-resistant lung cancer cell lines and lung cancer patient-derived organoids to demonstrate the potential of dauricine, a bioactive compound derived from menispermum dauricum, to overcome osimertinib resistance in lung cancer cells. Mechanistic studies reveal that dauricine, when combined with osimertinib, efficiently induces ferroptosis in resistant lung cancer cells. Notably, RNA interference and pharmacological inhibition assays identify SAT1, a key enzyme involved in polyamine metabolism and oxidative stress regulation, as a critical mediator of the synergistic effects observed with the dauricine-osimertinib combination therapy. Furthermore, we show that dauricine can directly interact with and stabilize SAT1 to enhance its activity. In vivo, when administered with osimertinib, dauricine significantly suppresses tumor growth in osimertinib-resistant lung cancer models. These findings provide novel insights into the role of SAT1 in overcoming osimertinib resistance and suggest that combining dauricine with osimertinib could be a promising therapeutic strategy to improve the efficacy of EGFR-TKI therapy in resistant NSCLC.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 8","pages":"2256-2269"},"PeriodicalIF":4.3,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Histone Methyltransferase SETDB1 in Normal and Malignant Hematopoiesis","authors":"Yu-Hsuan Chang,&nbsp;Susumu Goyama","doi":"10.1111/cas.70116","DOIUrl":"10.1111/cas.70116","url":null,"abstract":"<p>SET domain bifurcated histone methyltransferase 1 (SETDB1) is a histone H3 lysine 9 (H3K9) methyltransferase, functioning in transcriptional silencing of the transposable elements (TEs), endogenous retroviruses (ERVs), interferon-stimulated genes (ISGs), and immune cell-related molecules. SETDB1 collaborates with cofactors such as ATF7IP and TRIM28 and functions in concert with DNA methylation to maintain gene repression in both stem cells and differentiated somatic cells. Given its gene targets, recent studies have shown that SETDB1 is a critical immune checkpoint gene in both solid and hematological tumors. In this review, we first discuss the role of SETDB1 in gene regulation through its histone methyltransferase activity, including an overview of its structural features and key cofactors. We then highlight the lineage-specific roles of SETDB1 in both normal hematopoietic processes and hematological malignancies, emphasizing its function as an immune checkpoint molecule that suppresses natural killer (NK) cell-mediated antileukemia responses.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 9","pages":"2331-2339"},"PeriodicalIF":4.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Profiling Reveals the Distinctions Among MTX-Associated DLBCL, EBV-Positive Mucocutaneous Ulcer, and EBV + DLBCL","authors":"Takumi Takahashi,&nbsp;Keisuke Sawada,&nbsp;Takahisa Yamashita,&nbsp;Wataru Yamamoto,&nbsp;Yosuke Iijima,&nbsp;Akiko Adachi,&nbsp;Makoto Kashimura,&nbsp;Takayuki Tabayashi,&nbsp;Masahiro Kizaki,&nbsp;Takahiro Kaneko,&nbsp;Jun-ichi Tamaru,&nbsp;Morihiro Higashi,&nbsp;Shuji Momose","doi":"10.1111/cas.70111","DOIUrl":"10.1111/cas.70111","url":null,"abstract":"<p>The WHO recently changed the outline of immunodeficiency/dysregulation (IDD)-associated lymphoproliferative disorders (LPDs)/lymphomas from underlying IDD settings to an overarching framework and accommodates commonalities in histology, the involvement of various oncogenic viruses, and specific clinical/therapeutic consequences. A mutational analysis has been performed on post-transplantation and HIV-positive lymphomas, but not on other iatrogenic immunodeficiency (OII)-associated LPDs mainly caused by methotrexate (MTX) to treat rheumatoid arthritis. We herein conducted next-generation sequencing (NGS) to examine the genetic spectrum along with a fluorescence in situ hybridization analysis of 9p24.1 and PD-L1 expression in 37 MTX-associated diffuse large B-cell lymphoma (DLBCL) cases, 17 Epstein–Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) cases, and 26 EBV-positive DLBCL (EBV + DLBCL) cases. Targeted NGS identified 177 mutations. The mutation frequency was significantly higher in EBV⁻ MTX-DLBCL than in EBV-positive LPDs/lymphomas (EBVMCU, EBV⁺ MTX-DLBCL, and EBV + DLBCL). Regrowth or resistance to spontaneous regression after MTX withdrawal was more likely in EBV⁻ MTX-DLBCL than in EBV⁺ MTX-DLBCL. Therefore, accumulated gene mutations, sustained by the restored immune status in EBV⁻ MTX-DLBCL, may affect clinical outcomes after MTX discontinuation. Several unique genetic findings were obtained for each category. Fewer <i>TET2/DNMT3A</i> and <i>CD58</i> mutations in OII-LPD/lymphomas (EBVMCU and MTX-DLBCL) than in EBV + DLBCL indicate that clonal hematopoiesis and an immune evasion-related background contributed less to lymphomagenesis in OII-LPDs. <i>MYD88</i>^L265P/<i>CD79B</i>^Y196 mutations were only detected in EBV⁻ MTX-DLBCL. <i>SOCS1</i> mutations were significantly more frequent in EBV-positive LPD/lymphoma categories, irrespective of the immune status, than in EBV⁻ MTX-DLBCL. These results reveal distinct genetic features among MTX-DLBCL (EBV+/−), EBVMCU, and EBV + DLBCL.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 8","pages":"2306-2316"},"PeriodicalIF":4.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70111","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Landscape Analysis of CLDN18 Expression and Isoform Distribution in Solid Tumors: Insights From MONSTAR-SCREEN-2 Study","authors":"Tadayoshi Hashimoto,&nbsp;Naoko Iida,&nbsp;Yoshiaki Nakamura,&nbsp;Norio Nonomura,&nbsp;Chigusa Morizane,&nbsp;Hiroji Iwata,&nbsp;Susumu Okano,&nbsp;Wataru Yamagami,&nbsp;Naoya Yamazaki,&nbsp;Shigenori Kadowaki,&nbsp;Makoto Ueno,&nbsp;Shogen Boku,&nbsp;Eiji Oki,&nbsp;Yoshito Komatsu,&nbsp;Satoshi Yuki,&nbsp;Akitaka Makiyama,&nbsp;Takatsugu Ogata,&nbsp;Naoki Takahashi,&nbsp;Naohiro Okano,&nbsp;Tomohiro Nishina,&nbsp;Naoya Sakamoto,&nbsp;Takeshi Kuwata,&nbsp;Riu Yamashita,&nbsp;Taro Shibuki,&nbsp;Mitsuho Imai,&nbsp;Takao Fujisawa,&nbsp;Hideaki Bando,&nbsp;Kohei Shitara,&nbsp;Takayuki Yoshino","doi":"10.1111/cas.70100","DOIUrl":"10.1111/cas.70100","url":null,"abstract":"<p>Claudin 18.2 (CLDN18.2), a tight junction protein isoform, is an emerging therapeutic target in oncology. CLDN18 is well-characterized in gastric cancer, but its pan-cancer expression profiles and isoform distributions are poorly documented. In the present study, we analyzed CLDN18 expression in patients with solid tumors enrolled in the MONSTAR-SCREEN-2 study using immunohistochemistry (IHC, <i>n</i> = 349) and whole-transcriptome sequencing (WTS, <i>n</i> = 2191). A splice junction analysis algorithm characterized isoform distribution patterns in WTS data and evaluated temporal changes using paired pre- and postchemotherapy specimens. IHC detected CLDN18.2 (≥ 40% of tumor cells showing any staining intensity) in 16.3% of patients, with highest prevalence in gastric (54.5%), biliary tract (21.7%), pancreatic (20.7%), and small intestinal (18.2%) cancers. WTS and IHC findings were significantly correlated (<i>p</i> &lt; 0.001). WTS analysis with optimized transcript thresholds (<i>n</i> = 2191) demonstrated the <i>CLDN18</i>-high population to be 13.8%, with highest proportions in gastric (64.5%), small intestinal (40.0%), pancreatic (37.8%), and biliary tract (20.0%) cancers. Isoform analysis of 364 patients revealed <i>CLDN18.2</i> predominance (mean 18.2/18.1 proportion 0.945), with <i>CLDN18.1</i> predominance observed in only 4.9% of patients. Longitudinal analysis of 27 paired gastric cancer samples revealed a significant reduction in <i>CLDN18</i> expression and a nonsignificant decrease in the <i>CLDN18.2</i> proportion following chemotherapy. This analysis validates WTS as a complementary approach to IHC for CLDN18 assessment and demonstrates significant <i>CLDN18</i> expression across multiple cancer types. The predominance of <i>CLDN18.2</i> supports the expansion of targeted therapeutic approaches beyond gastric cancer and indicates the potential of RNA-based screening.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 8","pages":"2218-2231"},"PeriodicalIF":4.3,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ACSM5 Regulates Ferroptosis in Hepatocellular Carcinoma by Up-Regulating POR and Modulating Lipid Metabolism","authors":"Zhengqiang Wu,&nbsp;Xiaofeng Xiong,&nbsp;Mingyi Dong,&nbsp;Linfei Luo,&nbsp;Zixiang Huang,&nbsp;Kedong Xu,&nbsp;Lianwu Zhao,&nbsp;Fenfen Wang,&nbsp;Zhili Wen","doi":"10.1111/cas.70115","DOIUrl":"10.1111/cas.70115","url":null,"abstract":"<p>The medium-chain fatty acyl-CoA synthetase-5 (ACSM5) plays a crucial role in the development of some cancers. However, its impact on liver cancer is still not clear. In this study, we found that the proliferation ability of LM3 and HepG2 cells was significantly inhibited after ACSM5 was overexpressed, and this change was blocked by the ferroptosis inhibitor deferoxamine. ACSM5 increased the levels of malondialdehyde (MDA) and lipid reactive oxygen species (ROS), reduced the level of glutathione (GSH), and thus triggered ferroptosis. Furthermore, ACSM5 promoted the upregulation of cytochrome P450 oxidoreductase (POR). Knocking down POR blocked the promoting effect of ACSM5 on ferroptosis in HCC. Moreover, ACSM5 promoted the generation of arachidonic acid and thus increased the sensitivity to ferroptosis. In summary, our findings indicate that ACSM5 induces ferroptosis in hepatocellular carcinoma (HCC) by upregulating POR. The metabolic transformation of linoleic acid to arachidonic acid was also promoted by ACSM5; therefore, sensitivity to ferroptosis was increased.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 8","pages":"2125-2136"},"PeriodicalIF":4.3,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Connexin43 Promotes the Invasion and Metastasis of Lung Squamous Cell Carcinoma via GJIC-Dependent Ca2+/ERK Signaling Activation","authors":"Xiaocheng Mo,&nbsp;Jingchuan He,&nbsp;Xiaoju Shen,&nbsp;Changsheng Li,&nbsp;Xiaoxiang Mo,&nbsp;Kai Liang,&nbsp;Liangjun He,&nbsp;Tingting Li,&nbsp;Xiaoqin Pan,&nbsp;Sisi Cao,&nbsp;Naiquan Mao,&nbsp;Shangping Xing,&nbsp;Zhiquan Chen,&nbsp;Zhuo Luo,&nbsp;Jie Yang","doi":"10.1111/cas.70076","DOIUrl":"10.1111/cas.70076","url":null,"abstract":"<p>Lung squamous cell carcinoma (LUSC) is an extremely metastatic cancer with limited available treatment and poor outcomes. Connexin43 (Cx43) is frequently overactivated and positively correlated with tumorigenesis in many cancers, including breast cancer and lung adenocarcinoma, but its role in LUSC remains elusive. In this study, we demonstrated that Cx43 was highly expressed in LUSC tissues as compared to matching normal lung tissues (<i>n</i> = 103) and negatively related to prognosis. Through the 3D spheroid cell invasion assay, zCDX (zebrafish cell line-derived xenograft), and orthotopic lung cancer xenograft model, we further revealed that Cx43 promotes LUSC invasion and migration via forming GJIC. Knockdown of Cx43 reduced the Ca²⁺ transmission and ERK phosphorylation, whereas the addition of Ca²⁺ enhanced ERK phosphorylation and promoted LUSC invasion and migration. Furthermore, verapamil (40 μM and 80 μM), a calcium channel inhibitor, significantly inhibited ERK phosphorylation as well as the invasion and migration of LUSC cells. Mechanistically, Cx43 promoted the invasion and metastasis of LUSC via activating the Ca²⁺/ERK signaling pathway by gap junctional intracellular communication (GJIC). Our findings provide a novel mechanism insight for LUSC invasion and migration and a proof of concept for a new therapeutic strategy to tackle this disease.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 8","pages":"2086-2100"},"PeriodicalIF":4.3,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diversity of U1 Small Nuclear RNAs and Diagnostic Methods for Their Mutations","authors":"Takuma Nakashima,&nbsp;Tsubasa Miyauchi,&nbsp;Ryota Takeuchi,&nbsp;Yuriko Sugihara,&nbsp;Yusuke Funakoshi,&nbsp;Fumiharu Ohka,&nbsp;Sachi Maeda,&nbsp;Junko Hirato,&nbsp;Takako Yoshioka,&nbsp;Hajime Okita,&nbsp;Yoshitaka Narita,&nbsp;Yonehiro Kanemura,&nbsp;Yasuhiro Kojima,&nbsp;Yuko Watanabe,&nbsp;Ryuta Saito,&nbsp;Hiromichi Suzuki","doi":"10.1111/cas.70110","DOIUrl":"10.1111/cas.70110","url":null,"abstract":"<p>U1 small nuclear RNA (snRNA) mutations are recurrent non-coding alterations found in various malignancies, yet their identification has proven challenging due to their repetitive nature. We characterized the complex interindividual diversity and genomic architecture of U1 snRNA loci using sequencing data and a pangenome reference. Our analysis uncovered copy number variations and the diversity of single-nucleotide variants in regions not predicted to have significant functional impact. Compared to traditional linear reference-based analyses for mutations, the pangenome graph demonstrated the best accuracy, successfully identifying previously undetectable mutations. This underscores the utility of pangenome graph references for cancer genome research, particularly in repetitive and highly diverse genomic regions. Additionally, we developed mutation detection methods employing targeted capture sequencing, rapid quantitative polymerase chain reaction, and a machine learning approach based on splicing patterns, all exhibiting high precision in identifying U1 snRNA mutations. Our findings elucidate the structural complexity of U1 snRNA loci and establish robust methodologies for precise mutation detection in these regions.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 8","pages":"2270-2280"},"PeriodicalIF":4.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ligand-Receptor Interactions Between Squamous and Endothelial Cells Induce Head and Neck Squamous Cell Carcinoma","authors":"Takahiro Ishiyama,&nbsp;Daisuke Sano,&nbsp;Hideaki Takahashi,&nbsp;Nobuhiko Oridate,&nbsp;Yutaka Suzuki,&nbsp;Satoshi Fujii","doi":"10.1111/cas.70085","DOIUrl":"10.1111/cas.70085","url":null,"abstract":"<p>Advances in narrowband imaging (NBI) have revealed that squamous epithelial lesions form alongside changes in squamous epithelial cells and intrapapillary capillary loops (IPCLs) in the head and neck. However, the molecular interactions between squamous epithelial cells and endothelial cells (ECs) that promote IPCL proliferation are unclear. This study aimed to identify the mechanisms of cooperation between parenchymal squamous cells and stromal IPCLs during the formation of head and neck squamous cell carcinoma (SCC). We investigated ligand-receptor interactions between squamous epithelial and endothelial cells of IPCLs using Visium analysis on frozen, formalin-fixed and paraffin-embedded (FFPE) tissues from hypopharyngeal squamous epithelial lesions. We examined the protein expression in hypopharyngeal superficial squamous epithelial lesions using immunohistochemistry and immunofluorescence. mRNA expression levels of these genes in SCC and non-tumor tissues were analyzed using RT-qPCR. Phenotypic changes were analyzed by inducing candidate genes into SCC cell lines via a lentivirus system. Visium analysis revealed that <i>Fibronectin 1</i> (<i>FN1</i>) acted as a ligand in endothelial cells, <i>Cellular communication network factor 1</i> (<i>CCN1</i>) as a ligand in SCC cells, and <i>Integrin subunit alpha V</i> (<i>ITGAV</i>) as a receptor for both <i>FN1</i> and <i>CCN1</i>. The expression of these three candidates increased in low-grade dysplasia, an early stage of neoplastic lesions, and was significantly higher in invasive SCCs, except for CCN1. When <i>ITGAV</i> was introduced into SCC cell lines (FaDu and Detroit 562) and HaCaT cells treated with FN1, the cells showed increased proliferation ability. SCC develops via ligand-receptor molecular interactions between squamous epithelial and vascular endothelial cells in IPCLs.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 8","pages":"2296-2305"},"PeriodicalIF":4.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}