Cancer Science最新文献_第4页

Pan-immune-inflammation value predicts immunotherapy response and reflects local antitumor immune response in rectal cancer. 泛免疫炎症值可预测免疫疗法反应并反映直肠癌的局部抗肿瘤免疫反应。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-11-27 DOI: 10.1111/cas.16400

Qianyu Wang, Wentao Zhong, Yi Xiao, Guole Lin, Junyang Lu, Lai Xu, Guannan Zhang, Aijun Liu, Junfeng Du, Bin Wu

{"title":"Pan-immune-inflammation value predicts immunotherapy response and reflects local antitumor immune response in rectal cancer.","authors":"Qianyu Wang, Wentao Zhong, Yi Xiao, Guole Lin, Junyang Lu, Lai Xu, Guannan Zhang, Aijun Liu, Junfeng Du, Bin Wu","doi":"10.1111/cas.16400","DOIUrl":"https://doi.org/10.1111/cas.16400","url":null,"abstract":"The pan-immune-inflammation value reflects the systemic inflammatory response, and tumor-infiltrating lymphocytes indicate a local immune response in rectal cancer. However, the association between systemic inflammatory response, as indicated by the pan-immune-inflammation value, and local immune responses in rectal cancer remains unclear. This study analyzed 915 treatment-naïve rectal cancer patients from the Peking Union Medical College Hospital and PLA General Hospital (PLAGH) cohorts who underwent radical surgery to investigate the relationship between the pan-immune-inflammation value and immune responses. Lower pan-immune-inflammation value was significantly associated with improved disease-free survival and cancer-specific survival. Multivariate Cox regression models identified the pan-immune-inflammation value as an independent prognostic factor. In the PLAGH cohort, patients with low pan-immune-inflammation values had higher immune cell levels, activated immune pathways, and increased expression of immune checkpoint genes according to RNA sequencing. Hematoxylin and eosin staining and immunohistochemical analysis revealed that lower pan-immune-inflammation value was associated with higher tumor-infiltrating lymphocyte density, more mature tertiary lymphoid structures, increased CD8+ T cells, and elevated human lymphocyte antigen class I expression. Conversely, patients with high pan-immune-inflammation values exhibited pathways linked to tumor progression, such as angiogenesis, epithelial-mesenchymal transition, hypoxia, KRAS signaling, and TGF-ß signaling. Among patients receiving anti-PD-1 therapy, responders had low pre- and post-treatment pan-immune-inflammation values. The pan-immune-inflammation value is a reliable marker associated with distinct immune microenvironment characteristics and can effectively predict disease-free survival, cancer-specific survival, and response to immunotherapy.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142733772","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

TRIM47 promotes hypopharyngeal and laryngeal cancers progression through promoting K63-linked ubiquitination of vimentin. TRIM47 通过促进与 K63 链接的波形蛋白泛素化来促进下咽癌和喉癌的进展。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-11-25 DOI: 10.1111/cas.16397

Shichao Qin, Fen Chang, Xiangkai Sun, Zinan Li, Yin Wang, Dapeng Lei

{"title":"TRIM47 promotes hypopharyngeal and laryngeal cancers progression through promoting K63-linked ubiquitination of vimentin.","authors":"Shichao Qin, Fen Chang, Xiangkai Sun, Zinan Li, Yin Wang, Dapeng Lei","doi":"10.1111/cas.16397","DOIUrl":"https://doi.org/10.1111/cas.16397","url":null,"abstract":"Hypopharyngeal and laryngeal cancers which belong to head and neck squamous cell carcinoma (HNSCC) are the two most malignant types of head and neck cancer, characterized by a low 5-year survival rate, high recurrence and metastasis rate. It is vital to explore strategies to suppress metastasis and improve prognosis for patients with these cancers. In this research, we analyzed the clinical data and found that E3 ubiquitin ligase TRIM47 was upregulated in cancer tissues of hypopharyngeal cancer and was closely associated with poor survival outcomes. In terms of mechanism, we performed tandem affinity chromatography and denatured Ni-NTA Agarose pulldown. As a result, TRIM47 was found to interact with vimentin and control vimentin stabilization through ubiquitination, specifically in the form of K63 chains. Importantly, through experiments of cancer cell viability and migration, we found that TRIM47 could enhance the proliferation and metastasis abilities of cancer cells in a vimentin-dependent manner, thus promoting the advancement of hypopharyngeal and laryngeal cancers. TRIM47 was verified to regulate cancer cells metastasis in vivo using metastasis models. All these results imply that TRIM47 emerges as a potential biomarker for early diagnosis and metastasis prediction of hypopharyngeal and laryngeal cancers and represents a promising therapeutic target.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711648","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

S100A8 as a potential therapeutic target for cancer metastasis. S100A8 作为癌症转移的潜在治疗靶点。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-11-24 DOI: 10.1111/cas.16407

Atsuko Deguchi, Yoshiro Maru

引用次数: 0

Integrin-α5 expression and its role in non-small cell lung cancer progression. 整合素-α5的表达及其在非小细胞肺癌进展中的作用

IF 5.7 2区医学

Cancer Science Pub Date : 2024-11-24 DOI: 10.1111/cas.16416

Mirei Ka, Yoko Matsumoto, Takahiro Ando, Munetoshi Hinata, Qian Xi, Yuriko Sugiura, Takahiro Iida, Natsuki Nakagawa, Masakatsu Tokunaga, Kousuke Watanabe, Masanori Kawakami, Tetsuo Ushiku, Masaaki Sato, Katsutoshi Oda, Hidenori Kage

{"title":"Integrin-α5 expression and its role in non-small cell lung cancer progression.","authors":"Mirei Ka, Yoko Matsumoto, Takahiro Ando, Munetoshi Hinata, Qian Xi, Yuriko Sugiura, Takahiro Iida, Natsuki Nakagawa, Masakatsu Tokunaga, Kousuke Watanabe, Masanori Kawakami, Tetsuo Ushiku, Masaaki Sato, Katsutoshi Oda, Hidenori Kage","doi":"10.1111/cas.16416","DOIUrl":"https://doi.org/10.1111/cas.16416","url":null,"abstract":"Integrins are transmembrane receptors that facilitate cell adhesion to the extracellular matrix and neighboring cells. Aberrant expression of integrins has been associated with tumor progression and metastasis in various cancer types. Integrin alpha-5 (ITGA5) is an integrin subtype that serves as a receptor for fibronectin, fibrinogen, and fibrillin-1. The purpose of this study was to elucidate how ITGA5 expression plays a role in human non-small cell lung cancer (NSCLC). Our clinical data, along with data retrieved from The Cancer Genome Database (TCGA), revealed that high ITGA5 expression in NSCLC patients was associated with a lower recurrence-free survival and overall survival. In our in vitro functional assays, ITGA5 overexpression in human NSCLC cell lines resulted in increased cell size, adhesion, and migration properties, while knockdown of ITGA5 restored the phenotypes. Correspondingly, knockdown and inhibition of ITGA5 in endogenously high-expressing NSCLC cell lines resulted in decreased cell size, adhesion, migration, and proliferation. The antiproliferative effect was also confirmed by a reduction in Ki-67 without discernible changes in apoptosis. Collectively, these findings reveal the significant role of ITGA5 in various functional behaviors in NSCLC, providing a potential therapeutic target for NSCLC patients with high ITGA5 expression.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711641","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

LINC02154 promotes cell cycle and mitochondrial function in oral squamous cell carcinoma. LINC02154 促进口腔鳞状细胞癌的细胞周期和线粒体功能

IF 5.7 2区医学

Cancer Science Pub Date : 2024-11-22 DOI: 10.1111/cas.16379

Takeshi Niinuma, Hiroshi Kitajima, Tatsuya Sato, Toshifumi Ogawa, Kazuya Ishiguro, Masahiro Kai, Eiichiro Yamamoto, Yui Hatanaka, Iyori Nojima, Mutsumi Toyota, Akira Yorozu, Shohei Sekiguchi, Noritsugu Tohse, Masato Furuhashi, Hiroshi Ohguro, Akihiro Miyazaki, Hiromu Suzuki

{"title":"LINC02154 promotes cell cycle and mitochondrial function in oral squamous cell carcinoma.","authors":"Takeshi Niinuma, Hiroshi Kitajima, Tatsuya Sato, Toshifumi Ogawa, Kazuya Ishiguro, Masahiro Kai, Eiichiro Yamamoto, Yui Hatanaka, Iyori Nojima, Mutsumi Toyota, Akira Yorozu, Shohei Sekiguchi, Noritsugu Tohse, Masato Furuhashi, Hiroshi Ohguro, Akihiro Miyazaki, Hiromu Suzuki","doi":"10.1111/cas.16379","DOIUrl":"https://doi.org/10.1111/cas.16379","url":null,"abstract":"Long noncoding RNAs (lncRNAs) play pivotal roles in the development of human malignancies, though their involvement in oral squamous cell carcinoma (OSCC) remains incompletely understood. Using The Cancer Genome Atlas (TCGA) dataset, we analyzed expression of 7840 lncRNAs in primary head and neck squamous cell carcinoma (HNSCC) and found that upregulation of LINC02154 is associated with a poorer prognosis. LINC02154 knockdown in OSCC cell lines induced cell cycle arrest and apoptosis, and significantly attenuated tumor growth in vitro and in vivo. Notably, depletion of LINC02154 downregulated FOXM1, a master regulator of cell cycle-related genes. RNA pulldown and mass spectrometry analyses identified a series of proteins that could potentially interact with LINC02154, including HNRNPK and LRPPRC. HNRNPK stabilizes FOXM1 expression by interacting with the 3'-UTR of FOXM1 mRNA, which suggests LINC02154 and HNRNPK promote cell cycling by regulating FOXM1 expression. Additionally, LINC02154 positively regulates HNRNPK expression by inhibiting microRNAs targeting HNRPNK. Moreover, LINC02154 affects mitochondrial function by interacting with LRPPRC. Depletion of LINC02154 suppressed expression of mitochondrial genes, including MTCO1 and MTCO2, and inhibited mitochondrial respiratory function in OSCC cells. These results suggest that LINC02154 exerts its oncogenic effects by modulating the cell cycle and oxidative phosphorylation in OSCC, highlighting LINC02154 as a potential therapeutic target.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693844","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

Nelarabine-combined chemotherapy improves outcome of T-cell acute lymphoblastic leukemia but shows more severe neurotoxicity: JALSG T-ALL213-O. 奈拉滨联合化疗可改善T细胞急性淋巴细胞白血病的预后，但会产生更严重的神经毒性：JALSG T-ALL213-O。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-11-21 DOI: 10.1111/cas.16405

Fumihiko Hayakawa, Naoki Mori, Kiyotoshi Imai, Yasuhisa Yokoyama, Yuna Katsuoka, Takeshi Saito, Tohru Murayama, Etsuko Yamazaki, Shinya Sato, Yoshiko Atsuta, Yuichi Ishikawa, Emiko Sakaida, Yoshihiro Hatta, Itaru Matsumura, Yasushi Miyazaki, Hitoshi Kiyoi

{"title":"Nelarabine-combined chemotherapy improves outcome of T-cell acute lymphoblastic leukemia but shows more severe neurotoxicity: JALSG T-ALL213-O.","authors":"Fumihiko Hayakawa, Naoki Mori, Kiyotoshi Imai, Yasuhisa Yokoyama, Yuna Katsuoka, Takeshi Saito, Tohru Murayama, Etsuko Yamazaki, Shinya Sato, Yoshiko Atsuta, Yuichi Ishikawa, Emiko Sakaida, Yoshihiro Hatta, Itaru Matsumura, Yasushi Miyazaki, Hitoshi Kiyoi","doi":"10.1111/cas.16405","DOIUrl":"https://doi.org/10.1111/cas.16405","url":null,"abstract":"We investigated the effectiveness and safety of nelarabine (NEL)-combined chemotherapy for newly diagnosed adult T-cell acute lymphoblastic leukemia (T-ALL) patients. We conducted a phase II trial, T-ALL213-O, where adult T-ALL patients aged 25 to 64 were treated by a regimen based on that used in our previous study, ALL202-O. The main modifications from ALL202-O to T-ALL213-O were as follows: (1) NEL-combined chemotherapy, instead of consolidation (C)1, was used for non-complete remission (CR) patients after induction therapy (IND)1 as IND2; (2) NEL treatments were inserted into C3 and C5 on day 29. Twenty-four patients were analyzed. Ten patients did not receive NEL treatment due to therapy termination prior to C3. Three-year event-free survival (EFS) was 70%, with 52% as the lower limit of its 90% confidence interval, which exceeded the threshold of 25%; thus, the study treatment was considered effective. The CR rates by IND1, IND2, and both were 75%, 100%, and 88%, respectively. The 5-year EFS and 5-year overall survival rates were 66% and 70%, respectively, with median follow-ups of 7.7 and 7.8 years. The addition of NEL improved the CR rate but not survival, compared with T-ALL patients in ALL202-O. Severe neuropathy after NEL administration was observed at a high frequency. Seven (50%) of 14 patients treated with NEL showed grade 3 peripheral neuropathy and/or gait disturbance. The neurotoxicity was considered stronger than that previously reported. Combination therapy of NEL at this dose and intensive multidrug chemotherapy is associated with a high risk of severe neurotoxicity (JALSG T-ALL213-O, UMIN000010642).","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688861","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

Micropapillary structure: A natural tumor collective invasion model with enhanced stem-like properties. 微毛细血管结构：具有增强的干样特性的天然肿瘤集体侵袭模型。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-11-20 DOI: 10.1111/cas.16396

Sisi Li, Shuangshu Gao, Ling Qin, Caixia Ding, Jinghui Qu, Yifei Cui, Lixia Qiang, Shengjie Yin, Xiaoyu Zheng, Hongxue Meng

{"title":"Micropapillary structure: A natural tumor collective invasion model with enhanced stem-like properties.","authors":"Sisi Li, Shuangshu Gao, Ling Qin, Caixia Ding, Jinghui Qu, Yifei Cui, Lixia Qiang, Shengjie Yin, Xiaoyu Zheng, Hongxue Meng","doi":"10.1111/cas.16396","DOIUrl":"https://doi.org/10.1111/cas.16396","url":null,"abstract":"Cancer stem cells aggregate to form clusters, which have enhanced stem-like properties and metastasis potential. However, the molecular mechanisms underlying the formation of cancer stem cell cluster-like structures with acquisition of stronger invasion and metastasis abilities remain unclear. Micropapillary carcinoma (MPC) is a subpopulation of small, merulioid, inverted, nonfibrous vascular clusters floating in the stroma present in a range of solid malignant tumors and characterized by frequent vascular/lymphatic vessel invasion and lymph node metastasis. Our results showed that these cell clusters exhibit a stem cell phenotype, supporting the premise that MPC may serve as a promising solid tumor model for studying invasion and metastasis of cancer stem cell clusters. In this review, we discuss the latest advances in MPC research and targeted therapy, focusing on analysis of their stem-like characteristics, mapping their multiomics characteristics, and elucidating the vascular and immune microenvironment of MPC. The existing MPC organoid model was employed to explore potential breakthroughs in targeted therapy and immunotherapy for cancer stem cell clusters.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683228","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

Bacterial information in serum extracellular vesicles reflects the inflammation of adherent perinephric fat. 血清细胞外囊泡中的细菌信息反映了附着在肾周脂肪上的炎症。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-11-20 DOI: 10.1111/cas.16410

Toshihiro Uemura, Atsunari Kawashima, Kentaro Jingushi, Daisuke Motooka, Takuro Saito, Nesrine Sassi, Yuki Horibe, Akinaru Yamamoto, Yutong Liu, Masaru Tani, Akihiro Yoshimura, Toshiki Oka, Yohei Okuda, Gaku Yamamichi, Yu Ishizuya, Yoshiyuki Yamamoto, Taigo Kato, Koji Hatano, Kazutake Tsujikawa, Hisashi Wada, Norio Nonomura

{"title":"Bacterial information in serum extracellular vesicles reflects the inflammation of adherent perinephric fat.","authors":"Toshihiro Uemura, Atsunari Kawashima, Kentaro Jingushi, Daisuke Motooka, Takuro Saito, Nesrine Sassi, Yuki Horibe, Akinaru Yamamoto, Yutong Liu, Masaru Tani, Akihiro Yoshimura, Toshiki Oka, Yohei Okuda, Gaku Yamamichi, Yu Ishizuya, Yoshiyuki Yamamoto, Taigo Kato, Koji Hatano, Kazutake Tsujikawa, Hisashi Wada, Norio Nonomura","doi":"10.1111/cas.16410","DOIUrl":"https://doi.org/10.1111/cas.16410","url":null,"abstract":"Adipose tissue and bacterial flora are involved in metabolism in the human body. However, the relationship between the two remains unclear. Recently, the presence of circulating bacterial DNAs has been reported. We previously reported the utility of bacterial DNA in serum extracellular vesicles (EVs) for diagnosing patients with renal cell carcinoma (RCC). In this study, we aimed to assess whether there is a correlation between bacterial DNA in serum EVs and inflammation in adipose tissue. We undertook 16S rRNA metagenomic analysis of bacterial DNA in serum EVs from 77 patients with RCC (the derivation cohort). We discovered that DNAs from Enterobacteriaceae, Polaromonas, and Coxiellaceae were highly expressed in patients with low Mayo adhesive probability (MAP) scores. A lower MAP score reflects a reduced risk of dense adipose tissue and adhesions. Additionally, we combined these bacterial DNAs to create the EPC (Enterobacteriaceae, Polaromonas, Coxiellaceae) index that predicts a MAP score of 0. Subsequently, we undertook 16S rRNA metagenomic analysis of bacterial DNA in serum EVs from 32 patients with RCC (the validation cohort). The EPC index could distinguish patients with low MAP scores from those with high MAP scores in the derivation (area under the curve [AUC], 0.76; sensitivity, 56%; specificity, 85%) and validation (AUC, 0.81; sensitivity, 100%; specificity, 62%) cohorts. These results suggest that bacterial DNA in serum EVs could reflect the inflammation of adherent perinephric fat around the kidney.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683223","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

Leveraging genome-wide association studies to better understand the etiology of cancers. 利用全基因组关联研究更好地了解癌症病因。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-11-19 DOI: 10.1111/cas.16402

Kyuto Sonehara, Yukinori Okada

{"title":"Leveraging genome-wide association studies to better understand the etiology of cancers.","authors":"Kyuto Sonehara, Yukinori Okada","doi":"10.1111/cas.16402","DOIUrl":"https://doi.org/10.1111/cas.16402","url":null,"abstract":"Genome-wide association studies (GWAS) statistically assess the association between tens of millions of genetic variants in the whole genome and a phenotype of interest. Genome-wide association studies enable the elucidation of polygenic inheritance of cancer, in which myriad low-penetrance genetic variants collectively contribute to a substantial proportion of the heritable susceptibility. In addition to the robust genotype-phenotype associations provided by GWAS, combining GWAS data with functional genomic datasets or sophisticated statistical genetic methods unlocks deeper insights. Integrating genotype and molecular phenotyping data facilitates functional characterization of GWAS association signals through molecular quantitative trait loci mapping and transcriptome-wide association studies. Furthermore, aggregating genome-wide polygenic signals, including subthreshold associations, enables one to estimate genetic correlations across diverse phenotypes and helps in clinical risk predictions by evaluating polygenic risk scores. In this review, we begin by summarizing the rationale for GWAS of cancer, introduce recent methodological updates in the GWAS-derived downstream analyses, and demonstrate their applications to GWAS of cancers.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142677586","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

Rewired chromatin structure and epigenetic gene dysregulation during HTLV-1 infection to leukemogenesis. 从 HTLV-1 感染到白血病发生过程中的染色质结构改组和表观遗传基因失调。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-11-19 DOI: 10.1111/cas.16388

Jun Mizuike, Kako Suzuki, Shu Tosaka, Yuta Kuze, Seiichiro Kobayashi, Makoto Nakashima, Koji Jimbo, Yasuhito Nannya, Yutaka Suzuki, Kaoru Uchimaru, Makoto Yamagishi

{"title":"Rewired chromatin structure and epigenetic gene dysregulation during HTLV-1 infection to leukemogenesis.","authors":"Jun Mizuike, Kako Suzuki, Shu Tosaka, Yuta Kuze, Seiichiro Kobayashi, Makoto Nakashima, Koji Jimbo, Yasuhito Nannya, Yutaka Suzuki, Kaoru Uchimaru, Makoto Yamagishi","doi":"10.1111/cas.16388","DOIUrl":"https://doi.org/10.1111/cas.16388","url":null,"abstract":"Human T-cell leukemia virus type 1 (HTLV-1) broadly impacts host genes, affecting the infected cell population and inducing the development of a disease with a poor prognosis, adult T-cell leukemia-lymphoma (ATL). This study aimed to provide a comprehensive epigenomic characterization of the infected cell population and evaluated the transcriptome and chromatin structures of peripheral blood cells in HTLV-1-infected individuals using RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin sequencing (ATAC-seq). The infected cells showed significant changes in gene expression patterns from the polyclonal stage and before ATL onset while demonstrating similarities to tumor-forming ATL cells. These similarities were a result of large-scale open chromatin changes, supporting the independent early formation of epigenomic aberrations as an underlying mechanism for later clonal propagation. This study also demonstrated that HTLV-1 Tax directly affects the host chromatin structure, thereby developing fundamental epigenomic characteristics. Several Tax target genes, including the RASGRP3-ERK pathway, were recognized, indicating an impact on signaling pathways. This genome-wide variability in chromatin structural property is a novel feature of HTLV-1 infection and may contribute to pathogenic mechanisms. In addition, it has crucial implications for better understanding the impact of HTLV-1 on the host genome and identifying novel therapeutic targets.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142677587","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