Cancer Science最新文献

{"title":"The Clinical and Molecular Characterization of Distinct Subtypes in Adult T Cell Acute Lymphoblastic Leukemia","authors":"Heye Yu,&nbsp;Wenbing Liu,&nbsp;Junping Zhang,&nbsp;Leling Xie,&nbsp;Anli Lai,&nbsp;Zheng Tian,&nbsp;Kejing Tang,&nbsp;Haiyan Xing,&nbsp;Ying Wang,&nbsp;Hui Wei,&nbsp;Qing Rao,&nbsp;Runxia Gu,&nbsp;Min Wang,&nbsp;Huijun Wang,&nbsp;Jianxiang Wang,&nbsp;Shaowei Qiu","doi":"10.1111/cas.70010","DOIUrl":"10.1111/cas.70010","url":null,"abstract":"<p>T-cell acute lymphoblastic leukemia (T-ALL) is a clonal proliferative malignant disease characterized by abnormal T-cell development. The classification of T-ALL primarily hinges on immunophenotype, encompassing early T-cell precursor (ETP)-ALL, near-ETP-ALL, and non-ETP-ALL. We summarized clinical information from 117 patients, with genetic data available for 77 patients and transcriptomic data available for 24 patients. An ETP-like score model was established based on transcriptome, aiming to address the subjectivity in the current T-ALL immunophenotype classification. The retrospective analysis indicated that ETP immunophenotype was not a prognostic factor for T-ALL patients. Compared to non-ETP-ALL patients, ETP-like patients including ETP-ALL and near-ETP-ALL were more likely to carry <i>MED12</i> gene mutations, which may predict a dismal outcome. Transcriptomic analysis suggested that T-ALL patients with different immunophenotypes were in accordance with the T-cell development trajectory, while ETP-like patients exhibited characteristics of early T-cell development. Finally, we established an ETP-like score model and confirmed its efficiency across four independent cohorts, with sensitivity exceeding 80%. And T-ALL patients with high ETP-like score were associated with poor prognosis. In conclusion, our study elucidated the clinical and molecular features of distinct subtypes of T-ALL patients, providing new valuable insights for T-ALL classification.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 4","pages":"1126-1138"},"PeriodicalIF":4.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371269","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":"Abnormal Vessels Potentially Accelerate Glioblastoma Proliferation by Inducing the Protumor Activation of Macrophages","authors":"Hiroaki Matsuzaki,&nbsp;Keitaro Kai,&nbsp;Yoshihiro Komohara,&nbsp;Hiromu Yano,&nbsp;Cheng Pan,&nbsp;Yukio Fujiwara,&nbsp;Rin Yamada,&nbsp;Ai Iwauchi,&nbsp;Nei Fukasawa,&nbsp;Toshihide Tanaka,&nbsp;Masayuki Shimoda,&nbsp;Hiroshi Watanabe,&nbsp;Toru Maruyama,&nbsp;Toru Takeo,&nbsp;Yoshiki Mikami,&nbsp;Akitake Mukasa","doi":"10.1111/cas.70014","DOIUrl":"10.1111/cas.70014","url":null,"abstract":"<p>Glioblastoma (GBM) involves disruptions in the blood–brain barrier (BBB) and alterations in the immune microenvironment, including the activation of glioma-associated macrophages (GAMs). Vascular endothelial growth factor inhibitors, commonly used in recurrent GBM treatment, can influence these processes. This study investigates the relationship between BBB disruption and GAM activation, focusing on plasmalemma vesicle-associated protein (PLVAP), a marker of BBB disruption, and α1-acid glycoprotein (AGP), an inflammatory protein implicated in tumor progression. PLVAP expression was analyzed by immunohistochemistry (IHC) in human GBM samples to determine correlations with tumor grade, proliferation, and GAM activation. Pre- and post-bevacizumab treatment GBM samples were compared to assess changes in BBB integrity and macrophage activity. AGP's role in GAM activation was studied through in vitro assays and glioma implantation in AGP knockout mice, with assessments of tumor growth and angiogenesis. Results showed elevated PLVAP expression in higher-grade gliomas, correlating with increased tumor proliferation and GAM activation, particularly around PLVAP-positive vessels. Bevacizumab treatment reduced PLVAP expression and macrophage activity. AGP localized to regions of BBB disruption, promoting macrophage-mediated tumor growth in vitro. AGP knockout mice demonstrated reduced angiogenesis and prolonged survival. Spatial analysis revealed increased expression of macrophage-inducing molecules near PLVAP-positive vessels. These findings suggest PLVAP as a marker of BBB disruption and glioma malignancy. AGP, associated with BBB leakage, contributes to GAM activation and tumor progression, highlighting its potential as a therapeutic target for GBM.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 4","pages":"897-909"},"PeriodicalIF":4.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374751","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":"GD2 is a Crucial Ganglioside in the Signal Modulation and Application as a Target of Cancer Therapeutics","authors":"Koichi Furukawa,&nbsp;Yuhsuke Ohmi,&nbsp;Kazunori Hamamura,&nbsp;Yuki Ohkawa,&nbsp;Noboru Hashimoto,&nbsp;Orie Tajima,&nbsp;Kei Kaneko,&nbsp;Keiko Furukawa","doi":"10.1111/cas.70011","DOIUrl":"10.1111/cas.70011","url":null,"abstract":"<p>While various glycosphingolipids were identified as cancer-associated carbohydrate antigens to be used as tumor markers, disialylated gangliosides such as GD3 and GD2 have particularly attracted attention from many researchers as promising cancer-associated antigens. Simultaneously, their functions in cancer and normal tissues have also been reported. Although GD3 is expressed at the early neural developmental stage and in various cancers, it is also found in the activated status of some normal cells such as astrocytes and lymphocytes. On the other hand, GD2 is expressed in more restricted cells than GD3, enabling anti-GD2 immune therapy to be more applicable for immunotherapy. Recently, the expression of GD2 has been reported in various epithelial cancers and neuroectoderm-derived tumors. The involvement of GD2 in cancer stem cell propertiesand the roles of GD2 in the signal modulation to bring about cancer stemness are now some of the most fascinating research topics. Cancer immunotherapy targeting GD2 by anti-GD2 antibody or anti-GD2 CAR-T is now widely being challenged with various modifications such as combination with cytokines, chemotherapy, or immune checkpoint blocking.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 4","pages":"862-870"},"PeriodicalIF":4.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374763","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":"Antibody-Dependent Cellular Cytotoxicity of iPS Cell-Derived Natural Killer T Cells by Anti-GD2 mAb for Neuroblastoma","authors":"Katsuhiro Nishimura,&nbsp;Takahiro Aoki,&nbsp;Midori Kobayashi,&nbsp;Mariko Takami,&nbsp;Ko Ozaki,&nbsp;Keita Ogawa,&nbsp;Wang Hongxuan,&nbsp;Daiki Shimizu,&nbsp;Daisuke Katsumi,&nbsp;Hiroko Yoshizawa,&nbsp;Shugo Komatsu,&nbsp;Tomozumi Takatani,&nbsp;Kiyoshi Hirahara,&nbsp;Haruhiko Koseki,&nbsp;Tomoro Hishiki,&nbsp;Shinichiro Motohashi","doi":"10.1111/cas.70008","DOIUrl":"10.1111/cas.70008","url":null,"abstract":"<p>While antibody-dependent cellular cytotoxicity (ADCC) by anti-disialoganglioside GD2 monoclonal antibody (mAb) has succeeded in increasing the survival rate of high-risk patients with neuroblastoma, approximately 40%–50% of patients die from the disease. Recently, we developed induced pluripotent stem cell-derived natural killer T (iPS-NKT) cells, which exhibit NK-like cytotoxicity. However, whether iPS-NKT cells can induce ADCC function is unclear. Here, we investigated the ADCC of iPS-NKT cells and the efficacy of the combination treatment of anti-GD2 mAb and iPS-NKT cells against neuroblastoma. Anti-GD2 mAb enhanced the cytotoxicity and secretion of cytokines and cytotoxic granules of iPS-NKT cells, which expressed CD16 to GD2-expressing neuroblastoma cell lines. We also examined which Fcγ receptors contribute to ADCC of iPS-NKT cells. CD16 stimulation against iPS-NKT cells caused cytotoxicity and secretion of interferon-gamma, tumor necrosis factor, and granzyme B. In contrast, CD32 and CD64 stimulation did not. In vivo, the intratumor administration of anti-GD2 mAb and iPS-NKT cells significantly inhibited tumor growth compared with the other treatment groups: no treatment, anti-GD2 mAb alone, and iPS-NKT cells alone. In conclusion, iPS-NKT cells exhibit CD16-mediated ADCC, and the addition of iPS-NKT cells to anti-GD2 mAb therapy may be a potential approach for immunotherapy against neuroblastoma.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 4","pages":"884-896"},"PeriodicalIF":4.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366591","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":"AXL-Mediated Drug Resistance in ALK-Rearranged NSCLC Enhanced by GAS6 From Macrophages and MMP11 Positive Fibroblasts","authors":"Takahiro Utsumi,&nbsp;Hayato Mizuta,&nbsp;Yosuke Seto,&nbsp;Ken Uchibori,&nbsp;Makoto Nishio,&nbsp;Isamu Okamoto,&nbsp;Ryohei Katayama","doi":"10.1111/cas.70006","DOIUrl":"10.1111/cas.70006","url":null,"abstract":"<p>Anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC) shows marked tumor shrinkage by ALK-tyrosine kinase inhibitors (TKIs). However, tumors almost inevitably relapse owing to the development of acquired resistance. Resistance mechanisms include secondary ALK mutations and the activation of bypass pathways, such as cMET, cKIT, or EGFR, though some remain unknown. In this study, we analyzed alectinib-resistant patient samples and identified a significant increase in AXL expression in the tumor, and a high level of GAS6, the ligand for AXL, in the pleural effusion. AXL-overexpressing H3122 ALK-rearranged NSCLC cells exhibited partial resistance to alectinib, which was enhanced by GAS6 supplementation but could be overcome by the ALK/AXL inhibitor gilteritinib. Moreover, GAS6-overexpressing NIH3T3 cells and AXL-expressing H3122 cells were subcutaneously injected into the left and right sides of nude mice simultaneously, followed by alectinib treatment. The supply of GAS6 from NIH3T3 may have accelerated tumor relapse under alectinib treatment. However, even without GAS6-overexpressing NIH3T3, AXL-overexpressing H3122 tumor relapsed within 1 month possibly due to increased host mouse Gas6 expression. Single-cell RNA sequencing revealed that specific cancer-associated fibroblasts (CAFs) and a subset of tumor-associated macrophages (TAMs) are the primary sources of Gas6 in the tumor microenvironment (TME). During alectinib treatment, TAMs increased their infiltration into the TME, whereas CAFs altered their expression patterns, substantially upregulating Mmp11. These findings suggest that AXL expression in resistant cancer cells, combined with increased Gas6 production in the TME, contributes to enhanced ALK-TKI resistance.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 4","pages":"1034-1047"},"PeriodicalIF":4.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191116","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":"CML With Mutant ASXL1 Showed Decreased Sensitivity to TKI Treatment via Upregulation of the ALOX5-BLTR Signaling Pathway","authors":"Naoki Miyashita,&nbsp;Masahiro Onozawa,&nbsp;Kohei Kasahara,&nbsp;Toshihiro Matsukawa,&nbsp;Yasuhito Onodera,&nbsp;Kohjin Suzuki,&nbsp;Tomoiku Takaku,&nbsp;Takanori Teshima,&nbsp;Takeshi Kondo","doi":"10.1111/cas.70007","DOIUrl":"10.1111/cas.70007","url":null,"abstract":"<p>In this study, the mechanisms of tyrosine kinase inhibitor (TKI) resistance in chronic myeloid leukemia (CML) were investigated focusing <i>additional sex combs</i>-<i>like 1</i> (<i>ASXL1</i>) gene mutations and their downstream effects. While TKIs have improved the prognosis of CML, some patients have shown resistant to therapy. Cases with mutations in epigenome-related genes such as <i>ASXL1</i> are known to have a poor prognosis, but the underlying mechanisms of the poor prognosis are unclear. We showed that mutated <i>ASXL1</i> reduces TKI sensitivity in CML cell lines, and RNA microarray analysis revealed that <i>arachidonate 5</i>-<i>lipoxygenase</i> (<i>ALOX5</i>) is a significantly upregulated gene under the conditional expression of mutated <i>ASXL1</i>. Enforced <i>ALOX5</i> expression induced TKI resistance, while <i>ALOX5</i> knockout increased TKI sensitivity. <i>ALOX5</i> downstream signal inhibition by LY293111, a leukotriene B4 receptor (BLTR) antagonist, suppressed AKT phosphorylation and enhanced TKI sensitivity. This study revealed that TKI resistance in CML with <i>ASXL1</i> mutation was induced via <i>ALOX5</i> overexpression. <i>ASXL1</i> mutations may confer a clonal advantage through activation of the AKT pathway following <i>ALOX5</i> overexpression. While combined use of LY293111 with TKIs and asciminib showed synergistic effects against CML cells, the ALOX5-BLTR signaling pathway is novel therapeutic target for CML patients with mutated <i>ASXL1</i>.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 4","pages":"1115-1125"},"PeriodicalIF":4.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191118","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":"Susceptibility of Brca1(L63X/+) rat to ovarian reserve dissipation by chemotherapeutic agents to breast cancer","authors":"Satoshi Kaseki,&nbsp;Reina Sonehara,&nbsp;Yashiro Motooka,&nbsp;Hideaki Tanaka,&nbsp;Tomoko Nakamura,&nbsp;Satoko Osuka,&nbsp;Shinya Akatsuka,&nbsp;Hiroaki Kajiyama,&nbsp;Tomoji Mashimo,&nbsp;Tatsuhiko Imaoka,&nbsp;Shinya Toyokuni","doi":"10.1111/cas.16412","DOIUrl":"10.1111/cas.16412","url":null,"abstract":"<p><i>BRCA1</i> is one of the causative genes for hereditary breast and ovarian cancer syndrome with a high risk of early-onset breast cancer. Whereas olaparib (OLA), an inhibitor of poly-ADP-ribose polymerase, has been applied as adjuvant therapy to those cancer patients, its effect on ovarian reproductive function remains unelucidated. Recently, a rat model (MUT; <i>Brca1</i>^{<i>(L63X/+)</i>} mutation) mimicking a human <i>BRCA1</i> pathogenic variant has been established. Using this model, we evaluated the effects of OLA on ovarian reproductive function in comparison with the wild-type (WT) rats. MUT showed a significantly reduced number of primordial follicles and subfertility in accordance with aging. Oxidative stress was significantly elevated in the young MUT granulosa cells (GCs) accompanied by increased mTOR but decreased PTEN signals. OLA administration in MUT further decreased primordial follicles, with gene set enrichment analysis, indicating upregulated DNA repair pathways. Furthermore, a combination of OLA and cyclophosphamide (CPA) induced empty primordial follicles, recognized as CPA-induced severe ovarian toxicity. Whereas OLA + CPA caused greater reduction in primordial follicles both in MUT and WT in comparison with CPA alone, MUT ovaries were more susceptible to oxidative stress, potentially depleting primordial follicles via activation of GCs and inducing oocyte death due to accumulated DNA damage by OLA treatment. Our findings in this preclinical model underscore the importance of evaluating ovarian reserve prior to chemotherapy by performing reproductive consultation with female patients with <i>BRCA1</i> pathogenic variants.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 4","pages":"1139-1152"},"PeriodicalIF":4.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.16412","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123563","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":"Supersulfide metabolome of exhaled breath condensate applied as diagnostic biomarkers for esophageal cancer","authors":"Seji Asamitsu,&nbsp;Yohei Ozawa,&nbsp;Hiroshi Okamoto,&nbsp;Seiryo Ogata,&nbsp;Tetsuro Matsunaga,&nbsp;Jun Yoshitake,&nbsp;Kazuki Fusegawa,&nbsp;Yusuke Taniyama,&nbsp;Chiaki Sato,&nbsp;Hirotaka Ishida,&nbsp;Takaaki Abe,&nbsp;Hozumi Motohashi,&nbsp;Takaaki Akaike,&nbsp;Takashi Kamei","doi":"10.1111/cas.16430","DOIUrl":"10.1111/cas.16430","url":null,"abstract":"<p>Early detection of esophageal cancer is essential for esophagogastroduodenoscopy and histopathological diagnosis. However, endoscopic examinations are sometimes invasive, which limits their clinical application and compliance, and traditional blood tumor markers are unsuitable for cancer screening. The current study aimed to evaluate the usefulness of sulfur metabolites as new biomarkers for esophageal cancer using blood samples and exhaled breath condensate (EBC), which can be readily obtained and is non-invasive. We collected EBC and plasma samples from 50 patients with esophageal cancer and 30 healthy controls. Sulfur metabolome analysis using tandem mass spectrometry was performed to compare the metabolic profile between the two groups. Supersulfide metabolic profiles were different between the two cohorts. Supersulfide metabolome analysis showed that cysteine hydropersulfide (CysSSH) and homocysteine hydropersulfide (HomoCysSSH) were increased in the plasma of patients with esophageal cancer. Elevated levels of HomoCysSSH could distinguish patients with esophageal cancer from healthy subjects (area under the curve [AUC]: 0.93, sensitivity: 89%, specificity: 96%). Interestingly, we also detected an elevation of supersulfides in the EBC analysis. CysSSH levels significantly increased in the EBC recovered from patients with esophageal cancer (AUC: 0.71, sensitivity: 60%, specificity: 96%). In addition, the observed level was correlated with that of HomoCysSSH in the plasma (<i>r</i> = 0.27). Supersulfides, such as CysSSH and HomoCysSSH, are potential biomarkers for detecting esophageal cancer. CysSSH from EBC may serve as a valuable non-invasive biomarker with similar detection ability but with superior precision and convenience compared with the currently available blood biomarkers.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 4","pages":"1023-1033"},"PeriodicalIF":4.5,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.16430","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081723","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":"Genomic profiles of patients with skin melanoma in the era of immune checkpoint inhibitors","authors":"Yao Liang,&nbsp;Osamu Maeda,&nbsp;Kazuki Nishida,&nbsp;Basile Chretien,&nbsp;Yuichi Ando","doi":"10.1111/cas.16338","DOIUrl":"10.1111/cas.16338","url":null,"abstract":"<p>The use of immune checkpoint inhibitors (ICIs) for treating melanoma has dramatically improved patient prognosis. The genomic profiles of patients receiving ICI therapy would provide valuable information for disease management and treatment. We investigated the genomic profiles of patients with melanoma who had received ICI therapy and explored associations with clinical features and outcomes via a large-scale nationwide database in Japan (the C-CAT database). We identified 339 patients eligible for this study. The most frequent genetic mutations were found in the <i>BRAF</i> (27%), <i>TERT</i> (24%), and <i>NRAS</i> (19%) genes, and the most common copy number variations (CNVs) were in the <i>CDKN2A</i> (36%), <i>CDKN2B</i> (26%), and <i>MTAP</i> (19%) genes. Associations with high tumor mutational burden (TMB-high) status were significant for <i>TERT</i> (<i>p</i> &lt; 0.001), <i>NF1</i> (<i>p</i> &lt; 0.001), <i>ROS1</i> (<i>p</i> = 0.015), <i>POLE</i> (<i>p</i> = 0.045), and <i>POLD1</i> (<i>p</i> = 0.008) mutations, along with older age (≥65 years, <i>p</i> = 0.036). Patients with multiple metastases (two or more) were more likely to have <i>NOTCH3</i> mutations (<i>p</i> = 0.017) and be younger than 65 years (<i>p</i> = 0.024). In particular, as well as younger age, patients with brain metastases were more likely to harbor <i>BRAF</i> mutations (<i>p</i> &lt; 0.001), while those with liver metastases were more likely to harbor <i>NOTCH3</i> mutations (<i>p</i> &lt; 0.001) but not <i>CDKN2B</i> CNVs (<i>p</i> = 0.041). Patients with <i>NRAS</i> mutations were less likely to respond to ICI therapy (<i>p</i> = 0.014) and exhibited shorter overall survival (<i>p</i> = 0.006). In this population, the frequency of <i>BRAF</i> mutations was lower than that in fair-skinned populations, but the associations between genomic profiles, clinical features, and outcomes were similar to those previously reported in fair-skinned populations.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 4","pages":"1107-1114"},"PeriodicalIF":4.5,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.16338","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068756","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":"EXPRESSION OF CONCERN: Subtype-Specific Alterations of the Wnt Signaling Pathway in Breast Cancer: Clinical and Prognostic Significance","authors":"","doi":"10.1111/cas.16460","DOIUrl":"10.1111/cas.16460","url":null,"abstract":"<p><b>EXPRESSION OF CONCERN:</b> N. Mukherjee, N. Bhattacharya, N. Alam, A. Roy, S. Roychoudhury, and C.K. Panda, “Subtype-Specific Alterations of the Wnt Signaling Pathway in Breast Cancer: Clinical and Prognostic Significance,” <i>Cancer Science</i> 103, no. 2 (2012): 210–220, https://doi.org/10.1111/j.1349-7006.2011.02131.x.</p><p>This Expression of Concern is for the above article, published online on 25 October 2011, in Wiley Online Library (wileyonlinelibrary.com), and has been issued by agreement between the journal Editor-in-Chief, Masanori Hatakeyama; the Japanese Cancer Association; and John Wiley &amp; Sons Australia Ltd. The Expression of Concern has been agreed due to concerns raised by a third party after publication regarding the similarity of certain bands in Figure 2b and the underlying data that they represent. The authors could not provide the original data given the time that had elapsed since publication. Because the publisher was not able to examine the original data, it was not possible to investigate fully the concerns raised. Therefore, the journal is issuing this Expression of Concern because the concerns regarding the integrity of the data and the results presented cannot be resolved. Chinmay K. Panda agrees with this decision on behalf of the authors.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 4","pages":"1153"},"PeriodicalIF":4.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.16460","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034685","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}