Cancer Science最新文献

Correction to "Upregulation of HLA-II Related to LAG-3⁺CD4⁺ T Cell Infiltration is Associated With Patient Outcome in Human Glioblastoma". 更正“与LAG-3+CD4+ T细胞浸润相关的HLA-II上调与人胶质母细胞瘤患者预后相关”。

IF 5.7 2区医学

Cancer Science Pub Date : 2025-07-01 DOI: 10.1111/cas.70135

引用次数: 0

KLHL5 Contributes to Colorectal Cancer Cell Survival by Promoting Cell Cycle Progression and Suppressing Apoptotic Cell Death. KLHL5通过促进细胞周期进程和抑制凋亡细胞死亡参与结直肠癌细胞存活。

IF 5.7 2区医学

Cancer Science Pub Date : 2025-07-01 DOI: 10.1111/cas.70108

Kyosuke Habu, Yosuke Matsuoka, Hiromi Hiyoshi, Jun Nakayama, Katsuya Watanabe, Sota Tate, Tomohisa Sakaue, Junko Murai, Konomu Uno, Hirotada Nishie, Eiji Kubota, Hiromi Kataoka, Takashi Joh, Yuji Watanabe, Taro Oshikiri, Shigeki Higashiyama

{"title":"KLHL5 Contributes to Colorectal Cancer Cell Survival by Promoting Cell Cycle Progression and Suppressing Apoptotic Cell Death.","authors":"Kyosuke Habu, Yosuke Matsuoka, Hiromi Hiyoshi, Jun Nakayama, Katsuya Watanabe, Sota Tate, Tomohisa Sakaue, Junko Murai, Konomu Uno, Hirotada Nishie, Eiji Kubota, Hiromi Kataoka, Takashi Joh, Yuji Watanabe, Taro Oshikiri, Shigeki Higashiyama","doi":"10.1111/cas.70108","DOIUrl":"https://doi.org/10.1111/cas.70108","url":null,"abstract":"Kelch-like protein 5 (KLHL5) is highly expressed in colorectal cancer (CRC) compared to that in adjacent normal mucosa, and its expression level increases with CRC stage, showing a correlation with poor prognostic factors. However, its functional role in the malignant progression still remains unknown. To elucidate the role of KLHL5 in CRC, we characterized human CRC cell lines, including HCT116 and SW480, under KLHL5-depleted conditions. KLHL5-depleted HCT116 and SW480 cells suppressed their growth and migration in culture. Further duration induced cell death characterized by apoptotic cell death with down-regulation of antiapoptotic factor Bcl-2 and up-regulation of proapoptotic factors Bac, Boc, Puma, Bid, Noxa, and Bik. Proteomic analyses indicated KLHL5 depletion suppressed cell cycle progression by affecting multiple pathways, including the activation of the G2/M DNA damage pathway and inhibition of the G1/S transition. Further biochemical and cell biological analyses revealed the downregulation of CDT1 and CDC6 proteins, which are essential factors for the initiation of DNA replication, and the downregulation of cyclins A and B, which are essential factors for the progression of S and G2/M phases. Arrested cells undergo apoptotic cell death. Taken together, these data strongly indicate that KLHL5 expression in CRC serves as a survival factor to strengthen the cell cycle and protect against apoptotic cell death under harsh tumor microenvironments.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144545724","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

A 14-Gene Panel for Predicting Colorectal Cancer Recurrence Using Circulating Tumor DNA in Different Testing Conditions. 使用循环肿瘤DNA在不同测试条件下预测结直肠癌复发的14个基因小组。

IF 5.7 2区医学

Cancer Science Pub Date : 2025-06-30 DOI: 10.1111/cas.70114

Yuichi Hisamatsu, Koji Ando, Kensuke Kudo, Ryota Nakanishi, Tetsuro Kawazoe, Yoko Zaitsu, Tetsuya Kusumoto, Taishi Hata, Yoshinori Kagawa, Tomoharu Yoshizumi, Naoko Ashida, Hayato Niiro, Takashi Hirose, Eiji Oki

{"title":"A 14-Gene Panel for Predicting Colorectal Cancer Recurrence Using Circulating Tumor DNA in Different Testing Conditions.","authors":"Yuichi Hisamatsu, Koji Ando, Kensuke Kudo, Ryota Nakanishi, Tetsuro Kawazoe, Yoko Zaitsu, Tetsuya Kusumoto, Taishi Hata, Yoshinori Kagawa, Tomoharu Yoshizumi, Naoko Ashida, Hayato Niiro, Takashi Hirose, Eiji Oki","doi":"10.1111/cas.70114","DOIUrl":"https://doi.org/10.1111/cas.70114","url":null,"abstract":"Detecting minimal residual disease after surgery is critical for assessing colorectal cancer recurrence risk. Traditional methods, including histology and carcinoembryonic antigen testing, have limited sensitivity. As circulating tumor DNA has emerged as a promising minimal residual disease biomarker, we evaluated circulating tumor DNA detection using a sensitive, targeted 14-gene panel, the Sysmex Plasma-Safe-SeqS colorectal cancer assay, in resectable colorectal cancer cases. We enrolled 46 Japanese patients with preoperatively diagnosed stage II colorectal cancer who underwent surgery at three institutions. Plasma samples were collected pre- and postoperatively. Tumor-informed, plasma-informed, and tumor-naive Plasma-Safe-SeqS colorectal cancer assays were performed. Patients were followed for a median of 1169 (range 148-1476) days using clinical assessments and computed tomography scans. Variants in tumor tissue were detected in 45 of 46 cases (98%). Preoperative circulating tumor DNA was detected in 32 (70%) and postoperative circulating tumor DNA in 16 (35%) patients. Postoperative circulating tumor DNA predicted recurrence with 33%, 38%, and 25% of positive percent agreement for tumor-informed, plasma-informed, and tumor-naive assays, respectively. The tumor-naive assay detected more postoperative circulating tumor DNA-positive cases than the others. As the tumor-naive approach does not require preoperative genetic profiling, it offers significant advantages in cost and ease of implementation in routine clinical practice. Further large-scale studies are warranted to optimize detection strategies.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530613","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

Epigenetically-Upregulated CD98 Shed Light on the Precancerous Diagnosis and Prognosis Prediction of Esophageal Cancer. 表观遗传学上调CD98在食管癌癌前诊断和预后预测中的作用

IF 5.7 2区医学

Cancer Science Pub Date : 2025-06-30 DOI: 10.1111/cas.70128

Xue Zhang, Mengfei Sun, Na Li, Jie Yu, Wenjie Wang, Ju Yang, Hongyan Wu, Linyue Zhao, Huakun Zhang, Lan Yang, Feng Li, Qi Sun, Yunzhao Chen, Xiaobin Cui

{"title":"Epigenetically-Upregulated CD98 Shed Light on the Precancerous Diagnosis and Prognosis Prediction of Esophageal Cancer.","authors":"Xue Zhang, Mengfei Sun, Na Li, Jie Yu, Wenjie Wang, Ju Yang, Hongyan Wu, Linyue Zhao, Huakun Zhang, Lan Yang, Feng Li, Qi Sun, Yunzhao Chen, Xiaobin Cui","doi":"10.1111/cas.70128","DOIUrl":"https://doi.org/10.1111/cas.70128","url":null,"abstract":"Esophageal squamous cell carcinoma (ESCC) has a significantly low survival rate, primarily due to the lack of diagnostic markers for early diagnosis and effective therapies. Recently, CD98 has been proposed as a specific marker of mature esophageal basal cells, which may be associated with esophageal carcinogenesis. Therefore, we aimed to investigate the clinical significance and biological function of CD98 in ESCC progression, as well as the value of CD98 as a potential new marker for the early diagnosis of ESCC. Through MassARRAY system spectroscopy, DIA proteomics analysis, immunohistochemical and functional experiments, we found hypomethylation-linked upregulation of CD98 expression, which was associated with poor prognosis, promoted cell proliferation by regulating the cell cycle in ESCC. Furthermore, we not only demonstrated that the range of CD98 expression was consistent with that of dysplastic cells in 73.81% of low-grade intraepithelial neoplasia (LGIN) and 83.08% of high-grade intraepithelial neoplasia (HGIN) cases, but also confirmed the expression level of CD98 was positively correlated with the classical diagnosis marker P53. Compared to using P53 alone, the combination of the immunohistochemical markers CD98 and P53 (either one was positive) provided more accurate diagnostic data for LGIN (92.86% vs. 88.10%, p < 0.01) and HGIN (93.85% vs. 73.85%, p < 0.01). In summary, we propose that CD98 is involved in a crucial step in ESCC carcinogenesis, and when combined with P53, may serve as a diagnostic marker for ESCC precancerous lesions.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530614","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

SHBs Mitigates Sorafenib-Induced Apoptosis in Hepatocellular Carcinoma via Activation of RAF1/MEK/ERK Signaling Pathway. SHBs通过激活RAF1/MEK/ERK信号通路减轻索拉非尼诱导的肝癌细胞凋亡

IF 5.7 2区医学

Cancer Science Pub Date : 2025-06-28 DOI: 10.1111/cas.70132

Shuxiang Wu, Yuxiang Hong, Hang Li, Mengxian Lin, Xiaohuang Lin, Xinjian Lin, Xu Lin

{"title":"SHBs Mitigates Sorafenib-Induced Apoptosis in Hepatocellular Carcinoma via Activation of RAF1/MEK/ERK Signaling Pathway.","authors":"Shuxiang Wu, Yuxiang Hong, Hang Li, Mengxian Lin, Xiaohuang Lin, Xinjian Lin, Xu Lin","doi":"10.1111/cas.70132","DOIUrl":"https://doi.org/10.1111/cas.70132","url":null,"abstract":"Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide, with a significant association to hepatitis B virus (HBV) infection, which has been shown to drive HCC progression. Sorafenib, a multi-kinase inhibitor, is the first-line treatment for advanced HCC. However, recent studies indicate that HBV infection may confer resistance to sorafenib treatment. The small hepatitis B surface antigen (SHBs), the most abundant HBV viral protein, has been implicated in HCC development, yet its role in sorafenib resistance is unclear. This study demonstrates that SHBs promotes sorafenib resistance in HCC cells and xenograft models by inhibiting apoptosis. Upon sorafenib treatment, SHBs expression was found to enhance the RAF1/MEK/ERK signaling pathway, as evidenced by increased phosphorylation of ERK and MEK. Inhibition of ERK activity with U0126 countered SHBs effects on sorafenib-induced apoptosis, cleaved caspase-3, and cellular proliferation. Mechanistically, SHBs binds to protein tyrosine phosphatase non-receptor type 1 (PTPN1), enhancing its phosphorylation, which subsequently dephosphorylates the protein tyrosine phosphatase interacting protein 51 (PTPIP51). This dephosphorylation promotes RAF1 recruitment to the 14-3-3β complex, leading to activation of the RAF1/MEK/ERK pathway. These findings suggest that SHBs prevents sorafenib-induced apoptosis in HCC cells by binding to PTPN1 and stimulating the formation of the PTPIP51/14-3-3β/RAF1 complex, thereby activating the RAF1/MEK/ERK signaling pathway. This mechanism provides insight into HBV-induced sorafenib resistance in HCC, highlighting SHBs as a potential target for overcoming treatment resistance in HBV-related HCC.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530615","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-Associated Neutrophils Regulate Breast Cancer Progression Through the AQP9/STAT3 Signaling Pathway. 肿瘤相关中性粒细胞通过AQP9/STAT3信号通路调控乳腺癌进展

IF 5.7 2区医学

Cancer Science Pub Date : 2025-06-28 DOI: 10.1111/cas.70121

Wuqin Xu, Guilu Zhu, Youjing Sheng, Wenjun Zhang, Shujing Wang, Qiang Wu

{"title":"Tumor-Associated Neutrophils Regulate Breast Cancer Progression Through the AQP9/STAT3 Signaling Pathway.","authors":"Wuqin Xu, Guilu Zhu, Youjing Sheng, Wenjun Zhang, Shujing Wang, Qiang Wu","doi":"10.1111/cas.70121","DOIUrl":"https://doi.org/10.1111/cas.70121","url":null,"abstract":"Tumor-associated neutrophils (TANs) contribute to breast cancer (BC) progression, and aquaporin 9 (AQP9) plays a critical role in tumor development. However, the interactions between TANs and AQP9 in BC are poorly understood. Bioinformatics analyses and clinical samples revealed a positive correlation between neutrophil infiltration and AQP9 expression in BC. Treating BC cells with TAN-conditioned media significantly elevated AQP9 expression compared with neutrophil-conditioned and control media treatments. Immunohistochemical analysis revealed higher AQP9 protein expression in BC tissues than in adjacent normal tissues, and AQP9 expression was negatively correlated with recurrence-free survival and overall survival in patients with BC. Functional studies demonstrated that AQP9 promoted BC cell proliferation but did not affect migration or invasion. AQP9 knockdown markedly inhibited the ability of TANs to enhance BC cell proliferation, migration, and invasion. Intravenous and intratumoral injection of TANs in mice increased tumor growth rate, weight, and volume compared with controls; moreover, histological examination revealed lung metastasis in two mice and bone involvement in one mouse out of six in the TAN treatment group. AQP9 knockdown significantly reduced the tumor growth rate. In BC cells, TAN treatment elevated STAT3 phosphorylation, and this effect was amplified by AQP9 overexpression. In conclusion, TANs promote BC progression by enhancing STAT3 phosphorylation through AQP9 upregulation. AQP9 is crucial for TAN-mediated BC progression and is a potential target for immunotherapy in patients with BC.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530616","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

Correction to "Tumor Necrosis Factor-α Promotes the Lymphangiogenesis of Gallbladder Carcinoma Through Nuclear Factor-κB-Mediated Upregulation of Vascular Endothelial Growth Factor-C". 更正“肿瘤坏死因子-α通过核因子-κ b介导的血管内皮生长因子- c上调促进胆囊癌淋巴管生成”。

IF 5.7 2区医学

Cancer Science Pub Date : 2025-06-25 DOI: 10.1111/cas.70127

引用次数: 0

How Do Cancer Cells Create Cancer-Associated Fibroblast Subtypes? Impacts of Extracellular Vesicles on Stromal Diversity. 癌细胞如何产生与癌症相关的成纤维细胞亚型？细胞外囊泡对基质多样性的影响。

IF 5.7 2区医学

Cancer Science Pub Date : 2025-06-25 DOI: 10.1111/cas.70133

Yutaka Naito

引用次数: 0

PBK Expression Promotes the Aggressive Phenotypes of Mesothelioma. PBK表达促进间皮瘤侵袭性表型。

IF 5.7 2区医学

Cancer Science Pub Date : 2025-06-24 DOI: 10.1111/cas.70124

Kazumi Hori, Ichidai Tanaka, Tatsuhiro Sato, Mika Sato, Yuta Kodama, Hideyuki Itoigawa, Yuichi Abe, Taketo Kato, Ayumu Taguchi, Mitsuo Sato, Yoshitaka Sekido, Toyofumi Fengshi Chen-Yoshikawa, Makoto Ishii

{"title":"PBK Expression Promotes the Aggressive Phenotypes of Mesothelioma.","authors":"Kazumi Hori, Ichidai Tanaka, Tatsuhiro Sato, Mika Sato, Yuta Kodama, Hideyuki Itoigawa, Yuichi Abe, Taketo Kato, Ayumu Taguchi, Mitsuo Sato, Yoshitaka Sekido, Toyofumi Fengshi Chen-Yoshikawa, Makoto Ishii","doi":"10.1111/cas.70124","DOIUrl":"https://doi.org/10.1111/cas.70124","url":null,"abstract":"Mesothelioma is one of the most aggressive neoplasms worldwide that has a particularly poor prognosis. We have previously discovered that oxytocin receptors (OXTR) are highly expressed in mesothelioma and that OXTR knockdown significantly decreases the proliferation of mesothelioma cells with high OXTR expression. In this study, we performed quantitative proteomic profiling of two mesothelioma cell lines with high OXTR expression using mass spectrometry to investigate the downstream signals of OXTR in mesothelioma cells. We found that OXTR knockdown significantly downregulated PDZ-binding kinase (PBK)-a serine/threonine protein kinase belonging to the bispecific MAPKK family. PBK knockdown significantly suppressed proliferation, migration, and colony formation in mesothelioma cells with high PBK expression and decreased Akt and MAPK phosphorylation levels. Furthermore, immunohistochemical analysis of PBK in surgical specimens obtained from patients with mesothelioma showed that high PBK expression was strongly associated with poor overall survival (log-rank test p = 0.0031; hazard ratio 3.339 and 95% confidence interval 1.12-10.00) and recurrence-free survival (log-rank test p = 0.0024; hazard ratio 3.355 and 95% confidence interval 1.25-9.04). In addition, the clinical significance of PBK expression was validated in mesothelioma using datasets from TCGA. Multivariable Cox regression analysis, incorporating stage and OXTR mRNA expression, demonstrated that PBK mRNA expression was the strongest independent predictor of OS. Our findings indicate that PBK plays a crucial role in the aggressiveness of mesothelioma, making it a promising therapeutic target and potential prognostic biomarker for mesothelioma.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144486748","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

Correction to "lncRNA XLOC013218 Promotes Cell Proliferation and TMZ Resistance by Targeting the PIK3R2-Mediated PI3K/AKT Pathway in Glioma". 更正“lncRNA XLOC013218通过靶向胶质瘤中pik3r2介导的PI3K/AKT通路促进细胞增殖和TMZ耐药”。

IF 5.7 2区医学

Cancer Science Pub Date : 2025-06-23 DOI: 10.1111/cas.70131

引用次数: 0