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Human papillomavirus vaccine to prevent CIN3 or worse (CIN3+): A nationwide case-control study in Japan. 接种人类乳头瘤病毒疫苗预防 CIN3 或更严重(CIN3+):日本全国病例对照研究。
IF 5.7 2区 医学
Cancer Science Pub Date : 2024-10-25 DOI: 10.1111/cas.16375
Sayaka Ikeda, Yutaka Ueda, Asami Yagi, Taichi Mizushima, Akiko Sukegawa, Risa Kudoh, Manako Yamaguchi, Megumi Kurosawa, Etsuko Miyagi, Masayuki Sekine, Takayuki Enomoto
{"title":"Human papillomavirus vaccine to prevent CIN3 or worse (CIN3+): A nationwide case-control study in Japan.","authors":"Sayaka Ikeda, Yutaka Ueda, Asami Yagi, Taichi Mizushima, Akiko Sukegawa, Risa Kudoh, Manako Yamaguchi, Megumi Kurosawa, Etsuko Miyagi, Masayuki Sekine, Takayuki Enomoto","doi":"10.1111/cas.16375","DOIUrl":"https://doi.org/10.1111/cas.16375","url":null,"abstract":"<p><p>An increase in cervical cancer incidence has been reported in Japan. The Ministry of Health, Labor, and Welfare of Japan has resumed the active recommendation of regular HPV vaccines in 2022. In Japan, the preventive effect of CIN3+ in the real world has not yet been demonstrated in age-adjusted cohort or case-control studies. This study aimed to estimate the effect of the HPV vaccine against CIN3+ in Japanese women. This nationwide case-control study from April 2013 to March 2020 targeted women aged 20-26 years old at the time of cervical screening. We compared HPV vaccination exposure between those with abnormal and those with normal cytology. Abnormal cytology was classified into cervical intraepithelial neoplasia (CIN)1+, CIN2+, and CIN3+. We calculated the odds ratio (OR) and 95% confidence interval (CI) of the above endpoints and vaccination exposure using the conditional logistic regression model and estimated vaccine effectiveness using the formula (1 -OR) × 100. A total of 2790 cases and 13,990 controls (one-to-five matching) were eligible in 37 municipalities in Japan. In this study, 61 CIN3 (2.2%) and 10 squamous cell carcinomas (SCC) (0.4%) were found. The OR for CIN3+ versus controls was 0.14 (95% CI, 0.03-0.75), equating to a vaccine effectiveness of 86%. Of the 10 patients who had SCC none were vaccinated. This nationwide case-control study in Japan demonstrated a substantial risk reduction in CIN3+ among women who did versus those who did not receive HPV vaccination.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
FOXP3+/CD8+ ratio associated with aggressive behavior in RUNX3-methylated diffuse esophagogastric junction tumor. FOXP3+/CD8+比率与RUNX3甲基化弥漫性食管胃交界处肿瘤的侵袭行为有关
IF 5.7 2区 医学
Cancer Science Pub Date : 2024-10-23 DOI: 10.1111/cas.16373
Suguru Maruyama, Yu Imamura, Tasuku Toihata, Ikumi Haraguchi, Manabu Takamatsu, Makiko Yamashita, Yuichiro Nakashima, Eiji Oki, Kenichi Taguchi, Manabu Yamamoto, Shinji Mine, Akihiko Okamura, Jun Kanamori, Souya Nunobe, Takeshi Sano, Shigehisa Kitano, Tetsuo Noda, Masayuki Watanabe
{"title":"FOXP3+/CD8+ ratio associated with aggressive behavior in RUNX3-methylated diffuse esophagogastric junction tumor.","authors":"Suguru Maruyama, Yu Imamura, Tasuku Toihata, Ikumi Haraguchi, Manabu Takamatsu, Makiko Yamashita, Yuichiro Nakashima, Eiji Oki, Kenichi Taguchi, Manabu Yamamoto, Shinji Mine, Akihiko Okamura, Jun Kanamori, Souya Nunobe, Takeshi Sano, Shigehisa Kitano, Tetsuo Noda, Masayuki Watanabe","doi":"10.1111/cas.16373","DOIUrl":"https://doi.org/10.1111/cas.16373","url":null,"abstract":"<p><p>The tumor immune microenvironment is increasingly becoming a key consideration in developing treatment regimens for aggressive cancers, with evidence that regulatory T cells (Tregs) attenuate the antitumor response by interrupting cytotoxic T cells (CD8+). Here, we hypothesized the prognostic relevance of the proportions of Tregs (marked by forkhead box protein 3 [FOXP3]) and CD8+ cells in diffuse, non-Epstein-Barr virus (EBV)/non-microsatellite instability (MSI)-high gastroesophageal adenocarcinomas (GEAs), which are clinically characterized as more aggressive, immunologically inactive tumors as compared with their intestinal counterparts. Cell-count ratios of FOXP3+/CD8+ expression were calculated at the intratumoral region and invasive margin discretely on digital images from 303 chemo-naive non-EBV/non-MSI-high esophagogastric junction (EGJ) adenocarcinomas. A significant modifying prognostic effect of tumor histology was observed between 5-year EGJ cancer-specific survival and the FOXP3+/CD8+ ratio at the invasive margin in pStage I-III tumors (p for interaction = 0.022; hazard ratio [HR] = 8.47 and 95% confidence interval [CI], 2.04-35.19 for high ratio [vs. low] for diffuse; HR = 1.57 and 95% CI, 0.88-2.83 for high ratio [vs. low] for intestinal). A high FOXP3+/CD8+ ratio at the invasive margin was associated with RUNX3 methylation (p = 0.035) and poor prognosis in RUNX3-methylated diffuse histological subtype (5-year EGJ cancer-specific survival, 52.3% for high and 100% for low, p = 0.015). Multiomics data from The Cancer Genome Atlas linked CCL28 with RUNX3-suppressed diffuse histological subtypes of non-EBV/non-MSI-high GEA. Our data suggest that a high FOXP3+/CD8+ ratio at the invasive margin might indicate tumor immune escape via CCL28, particularly in the RUNX3-methylated diffuse histological subtype.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
P2RY6 deletion promotes UVB-induced skin carcinogenesis by activating the PI3K/AKT signal pathway. P2RY6 基因缺失可通过激活 PI3K/AKT 信号通路促进紫外线诱导的皮肤癌发生。
IF 5.7 2区 医学
Cancer Science Pub Date : 2024-10-22 DOI: 10.1111/cas.16378
Peng Xu, Tanglin Liu, Zile Yang, Kai Zang, Xiaoxuan Gao, Yuling Shi, Xiyun Ye, Yongyan Dang
{"title":"P2RY6 deletion promotes UVB-induced skin carcinogenesis by activating the PI3K/AKT signal pathway.","authors":"Peng Xu, Tanglin Liu, Zile Yang, Kai Zang, Xiaoxuan Gao, Yuling Shi, Xiyun Ye, Yongyan Dang","doi":"10.1111/cas.16378","DOIUrl":"10.1111/cas.16378","url":null,"abstract":"<p><p>Our previous research has demonstrated that P2RY6 functions as an oncogene in DMBA/TPA-induced two-stage chemical skin carcinogenesis in mice. However, considering that human skin cancer is predominantly attributed to UV radiation from sunlight, additional investigations are needed to elucidate the role of P2RY6 in UVB-induced skin carcinogenesis. Surprisingly, we found that P2ry6-deficient mice exhibited marked promotion to UVB-induced skin papilloma formation compared with wild-type mice, suggesting its tumor-suppressive role in UVB-induced skin cancer. Additionally, a P2ry6 gene knockout promoted skin hyperplasia induced by short-term UVB irradiation, while UDP, the ligand of P2RY6, could inhibit the short-term UVB-induced increase of epiderma thickness in mouse skin. Furthermore, UVB irradiation could significantly upregulate P2RY6 expression in human and mouse skin cells. These results indicated that P2RY6 may play a crucial protective role in resisting the UVB-induced formation of skin tumors. At the molecular level, the loss of the P2RY6 gene inhibits the ubiquitination modification and expression of XPC after UVB irradiation in skin keratinocytes, resulting in the accumulation of CPDs (cyclobutane pyrimidine dimers). We have also demonstrated that P2RY6 deletion activates the PI3K/AKT signaling pathway both in vitro and in vivo. The CPD accumulation and acute inflammatory response enhanced by the loss of the P2RY6 gene can be reversed by an AKT inhibitor. These findings suggest that P2RY6 may act as a tumor suppressor in UVB-induced skin cancer by regulating the PI3K/AKT signaling pathway.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Spheroid culture to select theoretical therapeutic drugs in intravascular large B-cell lymphoma. 用球孢子培养法筛选血管内大 B 细胞淋巴瘤的理论治疗药物。
IF 5.7 2区 医学
Cancer Science Pub Date : 2024-10-20 DOI: 10.1111/cas.16310
Mika Takai, Kazuyuki Shimada, Katsuya Furukawa, Yusuke Yamaga, Soichi Yoshiyama, Yusuke Kagaya, Takashi Suzuki, Kazuhiko Hayashi, Satoko Shimada, Kennosuke Karube, Hitoshi Kiyoi
{"title":"Spheroid culture to select theoretical therapeutic drugs in intravascular large B-cell lymphoma.","authors":"Mika Takai, Kazuyuki Shimada, Katsuya Furukawa, Yusuke Yamaga, Soichi Yoshiyama, Yusuke Kagaya, Takashi Suzuki, Kazuhiko Hayashi, Satoko Shimada, Kennosuke Karube, Hitoshi Kiyoi","doi":"10.1111/cas.16310","DOIUrl":"https://doi.org/10.1111/cas.16310","url":null,"abstract":"<p><p>Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal large B-cell lymphoma that is characterized by the proliferation of lymphoma cells in the lumina of small vessels. Recent progress uncovering the genetic characteristics associated with MYD88/CD79B mutations has stimulated interest in the use of drugs targeting B-cell receptor signaling, including Bruton's tyrosine kinase. However, difficulties in culturing ex vivo IVLBCL cells has hampered research on the development of novel therapies. In the present study, we demonstrated the establishment of an ex vivo culture system of IVLBCL cells obtained from patient-derived xenograft (PDX) models. The spheroid culture enabled us to culture IVLBCL PDX cells for more than 10 days and to explore the efficacy of drug treatments acting on these cells. We found that carfilzomib and ibrutinib were effective for treating IVLBCL in ex vivo experiments and conducted in vivo analyses to assess the efficacy of these drugs. Although the efficacy of carfilzomib was difficult to confirm due to its toxicity in our models, ibrutinib showed comparable efficacy to a standard combination of chemotherapy drugs. Together, our data provide a new culture method for IVLBCL PDX cells and a rationale for translating ibrutinib to clinical use in IVLBCL patients.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
SET facilitates immune escape of microsatellite stability colorectal cancer by inhibiting c-Myc degradation. SET 通过抑制 c-Myc 降解促进微卫星稳定性结直肠癌的免疫逃逸。
IF 5.7 2区 医学
Cancer Science Pub Date : 2024-10-17 DOI: 10.1111/cas.16368
Liping Gao, Yizhang Li, Haizhou Wang, Jialong Liu, Ranran Zhang, Wenqing Shan, Lingxiu Zeng, Qiu Zhao, Yong Li, Jing Liu
{"title":"SET facilitates immune escape of microsatellite stability colorectal cancer by inhibiting c-Myc degradation.","authors":"Liping Gao, Yizhang Li, Haizhou Wang, Jialong Liu, Ranran Zhang, Wenqing Shan, Lingxiu Zeng, Qiu Zhao, Yong Li, Jing Liu","doi":"10.1111/cas.16368","DOIUrl":"https://doi.org/10.1111/cas.16368","url":null,"abstract":"<p><p>Microsatellite stability (MSS) colorectal cancer (CRC) exhibits a low mutation load and poor immunogenicity, contributing to immune escape of tumor cells and less benefit from immune checkpoint blockade (ICB) treatment. The mechanisms underlying immunotherapeutic resistance in MSS CRC remain to be elucidated. Here, we identified that nuclear proto-oncogene SET is significantly higher expressed in MSS CRC compared to microsatellite instability (MSI) CRC and facilitates immune escape of MSS CRC. Mechanistically, SET represses the expression of C-C motif chemokine ligand 5 (CCL5) and upregulates mismatch repair (MMR) proteins expression in a c-Myc-dependent manner, which inhibits infiltration and migration of CD8<sup>+</sup> T cells to tumor tissues and results in low immunogenicity in MSS CRC. In addition, we found that SET impairs ubiquitination and proteasomal degradation of c-Myc by disrupting the interaction between E3 ligase FBXW7 and c-Myc. Moreover, SET inhibition enhances the response to immunotherapy in MSS CRC in vivo. Overall, this study reveals the critical roles and posttranslational regulatory mechanism of SET in immune escape and highlights the SET/c-Myc axis as a potential target for immunotherapy of MSS CRC that have implications for targeting a unique aspect of this disease.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Analysis of SLC genes alternative splicing identifies the SLC7A6 RI isoform as a therapeutic target for colorectal cancer. 对 SLC 基因替代剪接的分析发现,SLC7A6 RI 异构体是结直肠癌的治疗靶点。
IF 5.7 2区 医学
Cancer Science Pub Date : 2024-10-15 DOI: 10.1111/cas.16351
Chao Sun, Boning Zeng, Jilong Zhou, Nan Li, Mingwei Li, Chaowei Zhu, Shouxia Xie, Yifei Wang, Shaoxiang Wang, Xiao Wang
{"title":"Analysis of SLC genes alternative splicing identifies the SLC7A6 RI isoform as a therapeutic target for colorectal cancer.","authors":"Chao Sun, Boning Zeng, Jilong Zhou, Nan Li, Mingwei Li, Chaowei Zhu, Shouxia Xie, Yifei Wang, Shaoxiang Wang, Xiao Wang","doi":"10.1111/cas.16351","DOIUrl":"https://doi.org/10.1111/cas.16351","url":null,"abstract":"<p><p>Alternative splicing (AS), a crucial mechanism in post-transcriptional regulation, has been implicated in diverse cancer processes. Several splicing variants of solute carrier (SLC) transporters reportedly play pivotal roles in tumorigenesis and tumor development. However, an in-depth analysis of AS landscapes of SLCs in colon adenocarcinoma (COAD) is lacking. Herein, we analyzed data from The Cancer Genome Atlas and identified 1215 AS events across 243 SLC genes, including 109 differentially expressed AS (DEAS) events involving 62 SLC genes in COAD. Differentially spliced SLCs were enriched in biological processes, including transmembrane transporter activity, transporter activity, ferroptosis, and choline metabolism. In patients with COAD, tumor tissues exhibited higher expression of longer mitochondrial carrier SLC25A16 isoforms than adjacent normal tissues, consistent with bioinformatics analysis. Protein-coding sequences and transmembrane helices of survival-related DEAS were predicted, revealing that shifts in splicing sites altered the number and structure of their transmembrane proteins. We developed a prognostic risk model based on the screened 6-SLC-AS (SLC7A6_RI_37208 (SLC7A6-RI), SLC11A2_AP_21724, SLC2A8_ES_87631, SLC35B1_AA_42317, SLC39A11_AD_43204, and SLC7A8_AP_26712). Knockdown of the intronic region of SLC7A6-RI isoform enhanced colon cancer cell proliferation. In vivo, knockdown of the intronic region of SLC7A6-RI isoform enhanced tumor growth in colon cancer. Mechanistically, si-SLC7A6-RI isoform exerted oncogenic effects by activating the PI3K-Akt-mTOR signaling pathway and promoting cell proliferation, evidenced by increased expression of key regulators Phosphorylated Mammalian Target of Rapamycin (p-mTOR) and a cell proliferation marker Proliferating Cell Nuclear Antigen (PCNA) using western blotting. Our study elucidated SLC-AS in COAD, highlighting its potential as a prognostic and therapeutic target and emphasizing the suppressive influence of SLC7A6-RI in colon cancer progression.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification of sequence polymorphism in the D-loop region of mitochondrial DNA as a risk factor for breast cancer. 确定线粒体 DNA D 环区的序列多态性是乳腺癌的风险因素之一。
IF 5.7 2区 医学
Cancer Science Pub Date : 2024-10-14 DOI: 10.1111/cas.16353
Qian Nie, Wenzhe Zhang, Songping Lin, Meng Huang, Yan Li, Yibin Qiu, Jing Li, Xiaobin Chen, Yali Wang, Xin Tong, Jinqiao Wu, Peng He, Qindong Cai, Lili Chen, Minyan Chen, Wenhui Guo, Yuxiang Lin, Liuwen Yu, Jialin Hou, Weifeng Cai, Hanxi Chen, Chuan Wang, Fangmeng Fu
{"title":"Identification of sequence polymorphism in the D-loop region of mitochondrial DNA as a risk factor for breast cancer.","authors":"Qian Nie, Wenzhe Zhang, Songping Lin, Meng Huang, Yan Li, Yibin Qiu, Jing Li, Xiaobin Chen, Yali Wang, Xin Tong, Jinqiao Wu, Peng He, Qindong Cai, Lili Chen, Minyan Chen, Wenhui Guo, Yuxiang Lin, Liuwen Yu, Jialin Hou, Weifeng Cai, Hanxi Chen, Chuan Wang, Fangmeng Fu","doi":"10.1111/cas.16353","DOIUrl":"https://doi.org/10.1111/cas.16353","url":null,"abstract":"<p><p>Mitochondrial DNA (mtDNA) variations affect the efficiency of the electron transport chain and production of reactive oxygen species, contributing to carcinogenesis. The D-loop region of mtDNA has emerged as a variation hotspot region in human neoplasia; however, the potential contribution of these variations in breast cancer risk prediction remains unknown. We investigated the relationship between germline single nucleotide polymorphisms (SNPs) in the entire D-loop region and breast cancer risk in Chinese women. Peripheral blood-isolated mtDNA from 2329 patients with breast cancer and 2328 cancer-free controls was examined for SNPs. In the combined cohort, we used traditional risk factors, susceptibility germline polymorphisms, and logistic regression analysis to evaluate the predictive value of susceptibility variants for breast cancer risk. We calculated the area under the receiver operating characteristic curve (AUC) as a measure. We also measured the content of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Individual polymorphisms SNP573 were significantly associated with breast cancer risk in both the discovery and validation cohorts. In the combined cohort, the AUC of the traditional risk factors was 64.3%; after adding susceptibility variants, the AUC was 64.9% (DeLong test, p = 0.007). 8-OHdG levels were significantly higher in patients with breast cancer than in controls and higher in individuals with SNP573 than in those negative for this variation. Overall, oxidative stress might be associated with the risk of breast cancer, and SNP573 might be associated with oxidative stress. Our results indicate the risk potential of polymorphisms in the D-loop region in breast cancer in Southern China.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Benign polymorphisms in the BRCA genes with linkage disequilibrium is associated with cancer characteristics. 具有连锁不平衡的 BRCA 基因中的良性多态性与癌症特征相关。
IF 5.7 2区 医学
Cancer Science Pub Date : 2024-10-12 DOI: 10.1111/cas.16364
Kuo-Ting Lee, Dao-Peng Chen, Zhu-Jun Loh, Wei-Pang Chung, Chih-Yang Wang, Pai-Sheng Chen, Chun Hei Antonio Cheung, Chih-Peng Chang, Hui-Ping Hsu
{"title":"Benign polymorphisms in the BRCA genes with linkage disequilibrium is associated with cancer characteristics.","authors":"Kuo-Ting Lee, Dao-Peng Chen, Zhu-Jun Loh, Wei-Pang Chung, Chih-Yang Wang, Pai-Sheng Chen, Chun Hei Antonio Cheung, Chih-Peng Chang, Hui-Ping Hsu","doi":"10.1111/cas.16364","DOIUrl":"https://doi.org/10.1111/cas.16364","url":null,"abstract":"<p><p>Germline pathogenic mutation of the BRCA gene increases the prevalence of breast cancer. Reports on the benign variants of BRCA genes are limited. However, the definition of these variants might be altered with the accumulation of clinical evidence. Therefore, in the present study, we focused on benign single nucleotide polymorphisms (SNPs) of BRCA genes. Linkage disequilibrium was calculated from whole genome sequencing of the BRCA genes obtained from 500 healthy controls and 49 breast cancer patients. Sanger sequencing was used to confirm the mutation. The linkage disequilibrium was noted for seven and three SNPs in the BRCA1 and BRCA2 genes, respectively. Breast cancer with BRCA1/2 linkage disequilibrium was not correlated with a personal history of benign diseases or family history of cancer. Nevertheless, breast cancer with BRCA1 linkage disequilibrium was correlated with high tumor-infiltrating lymphocytes and positive extensive intraductal components. The patients with BRCA1 linkage disequilibrium tended to have worse disease-specific survival. Cancers with BRCA2 linkage disequilibrium are associated with a lower ratio of grade III cancer. Moreover, patients with BRCA2 linkage disequilibrium tended to have better overall survival. In conclusion, linkage disequilibrium from benign SNPs of the BRCA genes potentially affects cancer characteristics.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tumor immune microenvironment dynamics and outcomes of prognosis in non-muscle-invasive bladder cancer. 非肌层浸润性膀胱癌的肿瘤免疫微环境动态和预后结果
IF 5.7 2区 医学
Cancer Science Pub Date : 2024-10-11 DOI: 10.1111/cas.16333
Rei Kamitani, Nobuyuki Tanaka, Tadatsugu Anno, Tetsushi Murakami, Tsukasa Masuda, Yota Yasumizu, Toshikazu Takeda, Shinya Morita, Takeo Kosaka, Shuji Mikami, Kazuhiro Matsumoto, Mototsugu Oya
{"title":"Tumor immune microenvironment dynamics and outcomes of prognosis in non-muscle-invasive bladder cancer.","authors":"Rei Kamitani, Nobuyuki Tanaka, Tadatsugu Anno, Tetsushi Murakami, Tsukasa Masuda, Yota Yasumizu, Toshikazu Takeda, Shinya Morita, Takeo Kosaka, Shuji Mikami, Kazuhiro Matsumoto, Mototsugu Oya","doi":"10.1111/cas.16333","DOIUrl":"https://doi.org/10.1111/cas.16333","url":null,"abstract":"<p><p>Agents that target PD-1 and PD-L1 have been developed in the treatment of bladder cancer (BC). However, the diversity of immune cell infiltration in non-muscle-invasive BC (NMIBC) and the dynamics of the microenvironment as it progresses to muscle-invasive/metastatic disease remains unknown. To assess tumor immune activity, hierarchical clustering was applied to 159 BC samples based on cellular positivity for the defined immune cellular markers (CD3/CD4/CD8/FOXP3/CD20/PD-1/PD-L1/LAG3/TIGIT), divided into two clusters. There was a \"hot cluster\" (25%) consisting of patients with a high expression of these markers and a \"cold cluster\" (75%) comprising those without. The expression of CD39, CD44, CD68, CD163, IDO1, and Ki67 was significantly higher in tumors in the hot cluster. Immunologically, high-grade T1 tumors were significantly hotter, whereas tumors that had progressed to muscle invasion turned cold. However, a certain number of high-grade NMIBC patients were in the cold cluster, and these patients had a significantly higher risk of disease progression. Using an externally available TCGA dataset, RB1 and TP53 alterations were more frequently observed in TCGA hot cluster; rather FGFR3, KDM6A, and KMT2A alterations were common in TCGA cold/intermediate cluster. Analyses of recurrent tumors after BCG therapy revealed that tumor immune activity was widely maintained before and after treatment, and high FGFR3 expression was detected after recurrence in tumors initially classified into the cold cluster. Collectively, we revealed the dynamics of the tumor microenvironment in BC as a whole and identified candidate molecules as therapeutic targets for recurrent NMIBC, e.g., after BCG therapy.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prevalence and outcomes of germline pathogenic variants of homologous recombination repair genes in ovarian cancer. 卵巢癌中同源重组修复基因种系致病变异的发生率和结果。
IF 5.7 2区 医学
Cancer Science Pub Date : 2024-10-10 DOI: 10.1111/cas.16367
Maiko Miwa, Masakazu Kitagawa, Yuka Asami, Mayumi Kobayashi-Kato, Takafumi Watanabe, Aiko Ogasawara, Kengo Hiranuma, Hisamori Kato, Motonobu Saito, Yohei Miyagi, Tomoyasu Kato, Hiroshi Yoshida, Yukihide Momozawa, Takashi Kohno, Kouya Shiraishi, Kosei Hasegawa
{"title":"Prevalence and outcomes of germline pathogenic variants of homologous recombination repair genes in ovarian cancer.","authors":"Maiko Miwa, Masakazu Kitagawa, Yuka Asami, Mayumi Kobayashi-Kato, Takafumi Watanabe, Aiko Ogasawara, Kengo Hiranuma, Hisamori Kato, Motonobu Saito, Yohei Miyagi, Tomoyasu Kato, Hiroshi Yoshida, Yukihide Momozawa, Takashi Kohno, Kouya Shiraishi, Kosei Hasegawa","doi":"10.1111/cas.16367","DOIUrl":"https://doi.org/10.1111/cas.16367","url":null,"abstract":"<p><p>Germline pathogenic variants (PVs) are pivotal in gynecological oncology. We focused on the prevalence, clinicopathological features, and survival impact of homologous recombination repair (HRR) PVs in patients with epithelial ovarian cancer (EOC). This was a multicenter retrospective cohort study, and 1248 patients with EOC were registered. Eligible patients (n = 1112) underwent germline DNA analysis for 26 cancer predisposition genes, including nine HRR-related genes, such as BRCA1/2, BRIP1, PALB2, RAD51C/D, and ATM. The associations between clinicopathological factors and HRR-related PVs were examined. Kaplan-Meier and Cox regression analyses were conducted. Among 1091 analyzed patients, 153 (14.0%) carried PVs and 140 (12.8%) were HRR-related. HRR-PV-positive status significantly correlated with serous carcinoma (22.9% vs. 4.8%, P < 0.0001) and advanced disease (18.5% vs. 5.9%, P < 0.0001). The HRR-PV-positive group exhibited higher prevalence of personal breast (12.9%) and familial breast/ovarian (29.2%) cancer history. HRR status independently improved overall survival in stage III/IV disease (P = 0.04) but not progression-free survival. HRR-related germline PVs exhibit distinct clinicopathological features with survival implications. Variants were significantly associated with serous carcinoma and advanced disease, underscoring the importance of genetic testing to develop individualized EOC treatment strategies. Considering the study period (2000-2019), the limited use of bevacizumab and poly (ADP-ribose) polymerase inhibitors as maintenance therapy should be recognized.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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