Journal of Cancer最新文献

{"title":"Propofol reduces breast cancer cell stemness via FOXO3/SOX2 axis.","authors":"Wen-Qian Fang, Xiao-Bei Zhang, Yue Yu, Jie Ge, Ran Meng","doi":"10.7150/jca.104142","DOIUrl":"10.7150/jca.104142","url":null,"abstract":"<p><p><b>Objective:</b> Propofol is a common intravenous anesthetic in cancer resection surgery, which is considered to exhibit anti-tumor effect in various cancer types. This study was aimed at investigating the role and mechanism of propofol in breast cancer stemness and proliferation. <b>Methods:</b> The breast cancer cells with propofol treatment were sequenced. The expression of FOXO3 in propofol treated cells was detected by RT-qPCR and Western blot. The CSC properties were analyzed by screen cells with ESA⁺CD44⁺CD24^-/low through flow cytometry and the proliferation capacity were also detected. The expression correlation of FOXO3 and target genes were detected by western blot. The potential binding site of FOXO3 on SOX2 was predicted by JASPAR and verified by dual-luciferase reporter assay and ChIP assay. <b>Results:</b> FOXO3 was found to be upregulated in propofol 24h-treated cells. Propofol could inhibit the capacity of breast cancer cell stemness and proliferation by upregulation FOXO3, which inhibited SOX2 expression transcriptionally. <b>Conclusion:</b> In this study, we uncovered the role of propofol-FOXO3-SOX2 in breast cancer cell stemness and proliferation, which might serve as potential targets for breast cancer therapy.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 5","pages":"1555-1562"},"PeriodicalIF":3.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of MATN3 in Cancer Prognosis and Immune Infiltration Across Multiple Tumor Types.","authors":"Chongjiu Qin, Haifei Qin, Haixiang Xie, Yuhua Li, Aoyang Bi, Xiwen Liao, Kejian Yang, Chunmiao Lu, Tao Peng, Guangzhi Zhu","doi":"10.7150/jca.103523","DOIUrl":"10.7150/jca.103523","url":null,"abstract":"<p><p><b>Background:</b> MATN3 is a member of the matrix protein family and is involved in the regulation of osteoarthritis as well as the development of gastric cancer. We investigated the role of MATN3 in pan-cancer and validated this result by <i>in vitro</i> experiments. <b>Material and Methods:</b> We applied multiple databases to explore the expression of MATN3 in 33 types of tumors. Kaplan-Meier survival analysis is performed to understand the effect of MATN3 on Prognostic value in patients with different cancer types. The TIMER database was applied to explore the relationship between MATN3 and immune checkpoint genes, immunomodulatory genes, and immune infiltration, the Sanger box was applied to explore the relationship between MATN3 and methylation, the Genomic Cancer Analysis database was utilized to explore the relationship between MATN3 expression and pharmacological sensitivity, and the STRING database was used to explore the co-expressed genes and to complete the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Data from The Cancer Genome Atlas as well as Genotype-Tissue Expression databases were statistically analyzed and visualized using the R software. Immunohistochemistry and Western blotting for detection of MATN3 expression. CCK-8 and clone formation were used to detect cell proliferation, Wound-healing assay and transwell invasion were used to detect cell migration and invasion ability. <b>Results:</b> MATN3 is overexpressed in most cancer types, indicating a poorer prognosis. It is closely linked to methylation, immunomodulatory genes, and immune checkpoint genes, contributing to immune infiltration in various cancer types. <i>In vitro</i> experiments showed that silencing MATN3 inhibited cell proliferation, migration, and invasion ability. <b>Conclusions:</b> MATN3 is involved in the immune infiltration of cancer and affects the prognosis of many cancer types, and can be used as an immune as well as prognostic biomarker for pan-cancer.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 5","pages":"1519-1537"},"PeriodicalIF":3.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA C2orf27A Promotes Gastric Cancer by Sponging MiR-610 and Elevating NOX4 Expression.","authors":"Mingkai Zhuang, Xiaoxiong Guo, Dan Lin, Na Lin, Xiaozhong Wang, Fenglin Chen","doi":"10.7150/jca.100621","DOIUrl":"10.7150/jca.100621","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) are crucial for gastric cancer (GC) progression. In this study, we aimed to investigate the function and molecular pathways of lncRNA C2orf27A in GC development. Bioinformatics databases, tissue cDNA microarrays, and cell lines were used to assess the expression of C2orf27A in GC. Cell proliferation was assessed using Cell Counting Kit-8, colony formation, cell cycle assays, whereas cell death using the Annexin V-APC/7-AAD assay. Subcutaneous xenograft mouse models were used to assess the effects of the C2orf27A knockdown on GC growth <i>in vivo</i>. The subcellular localization of C2orf27A in GC cells was verified using nucleocytoplasmic separation. Bioinformatics analysis predicted the binding of C2orf27A, miR-610, and NADPH oxidase 4 (NOX4), which was validated using dual luciferase reporter gene assay. We found that C2orf27A expression increased in GC tissues and cells. Furthermore, GC patients with increased C2orf27A expression levels had worse survival rates. Silencing of C2orf27A suppressed GC cell growth and induced GC cell death <i>in vitro</i> and <i>in vivo</i>. Further investigations into underlying mechanisms showed that C2orf27A functions as a competitive endogenous RNA against miR-610, leading to increased NOX4 expression levels in GC cells. Notably, blocking miR-610 and increasing NOX4 expression levels reversed the anticancer effects of reduced C2orf27A levels in GC cells. In summary, C2orf27A promotes cell proliferation and reduces cell death through the miR-610/NOX4 pathway in GC, which may provide a new perspective for further elucidation of the molecular mechanism underlying GC progression.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 5","pages":"1504-1518"},"PeriodicalIF":3.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell Sequencing Reveals PD-L1-Mediated Immune Escape Signaling in Lung Adenocarcinoma.","authors":"Anbing Zhang, Jianping Liang, Xiaoli Lao, Xiuqiong Xia, Siqi Li, Shengming Liu","doi":"10.7150/jca.103656","DOIUrl":"10.7150/jca.103656","url":null,"abstract":"<p><p><b>Background:</b> Lung cancer has the highest mortality rate among all cancers, for which immunotherapy can frequently lead to drug resistance. To understand the molecular mechanisms behind immune escape in patients with lung cancer and develop predictive and therapeutic targets, we carried out analytical experiments using single-cell sequencing. <b>Methods:</b> We collected eight tumor tissue samples from eight patients with lung adenocarcinoma and categorized them based on the positive reactions for programmed cell death ligand 1 (PD-L1) expression levels. Single-cell sequencing analysis was employed to create a comprehensive cellular landscape. Uniform Manifold Approximation and Projection was used to show the proportion of immune and endothelial cells, along with a map depicting the distribution of different cell types. Cells were subdivided according to molecular markers; the subpopulations were grouped based on PD-L1 levels and tumor marker-positive reactions. The correlation between the occurrence of the PD-L1 reaction and the response time of immune cells was explored; differential gene expression between the groups was elucidated. Finally, quantitative polymerase chain reaction (qPCR) was used to examine the relationship between key differentially expressed genes and PD-L1 immune escape checkpoint response. <b>Results:</b> A total of 58,810 single cells were analyzed, identifying seven distinct cell types. In the PD-L1-positive sample group, B cells, astrocytes, endothelial cells, outer skin cells, and tissue stem cells were present in higher proportions, whereas T and dendritic cells were the main cells in the PD-L1-negative sample group. According to the molecular markers, the seven cell types were divided into 17 cell clusters, with one cluster classified as tumor cells, showing PD-L1 positivity. Eleven molecular markers with different expression levels were simultaneously screened (NAPSA, MUC1, WFDC2, MYO6, LYZ, IGHG4, IGLL5, IGHM, IGKC, AQP3, and IGFBP7), and their association with the PD-L1/PD-1 immune escape axis response was confirmed by qPCR. <b>Conclusion:</b> Our study suggests that PD-L1-mediated immune escape may occur at a later stage of tumor progression, involving both PD-L1-positive and negative immune cells. Additionally, we identified 11 differentially expressed genes that could provide insights into the potential mechanisms of immune escape in patients with lung cancer. These findings offer promising molecular targets for the detection and treatment of immune escape in clinical settings.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 5","pages":"1438-1450"},"PeriodicalIF":3.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Predictive Nomograms for Treatment Decision-Making in Resectable Synchronous Colorectal Liver Metastases.","authors":"Yujuan Jiang, Dedi Jiang, Jinghua Chen, Heting Feng, Zixing Zhu, Jun Jiang, Fan Wu, Jianwei Liang","doi":"10.7150/jca.107194","DOIUrl":"10.7150/jca.107194","url":null,"abstract":"<p><p><b>Background:</b> Currently, there is no established standard for managing resectable synchronous colorectal liver metastases (CRLM): upfront surgery or neoadjuvant therapy. This study has integrated four available clinical factors - clinicopathological characteristics, gene mutation profiles, imaging findings, and hematological indicators - to create a potentially robust tool aiding clinicians in deciding between upfront surgery and neoadjuvant therapy. <b>Methods:</b> This retrospective cohort study included individuals diagnosed with resectable synchronous CRLM between 2008 and 2018. The development of prediction nomograms entailed identifying independent prognostic indicators through univariate and multivariate Cox analyses. The accuracy of the predictions was evaluated through calibration curves and the C-index. Furthermore, the clinical effectiveness of the nomograms was assessed using DCA and ROC curves. To enhance accessibility, two web servers were developed to simplify the utilization of the nomograms for an improved user experience. <b>Results:</b> A total of 386 patients with resectable synchronous CRLM were included. The patients were categorized randomly into a training cohort (n = 270, 70%) and a testing cohort (n = 116, 30%). The nomograms incorporated nine predictors: metastatic tumor count, cN stage, KRAS and BRAF mutation status, age, primary tumor location, neutrophil and platelet counts, and D-Dimer levels. The calibration plots for resectable synchronous CRLM survival predictions showed remarkable consistency. The C-index of OS and DFS prediction models were both above 0.7. And the area under the ROC curve of 1-, 3- and 5-year OS and DFS exceeded 0.7 as well. As demonstrated by the DCA plots, both nomograms exhibit satisfactory clinical effectiveness. A web-based application was developed to demonstrate the practical application of the prediction models. <b>Conclusion:</b> The personalized web-based predictive models exhibited moderate predictive accuracy in resectable synchronous CRLM. These tools offer valuable assistance to physicians in deciding between upfront surgery and neoadjuvant therapy for resectable synchronous CRLM.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 5","pages":"1451-1465"},"PeriodicalIF":3.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intercellular Adhesion Molecule 3: Structure, Cellular Functions, and Emerging Role in Human Diseases.","authors":"Xinzhuang Shen, Dehong Luo, Xiaowen Yang, Yifei Li, Fuming Lian, Huan Liu, Xiaoyuan Zhang, Wenzhi Shen","doi":"10.7150/jca.100612","DOIUrl":"10.7150/jca.100612","url":null,"abstract":"<p><p>The intercellular adhesion molecule 3 (ICAM3), also known as CD50, is a member of the intercellular adhesion molecule (ICAM) family. All ICAM proteins are type I transmembrane glycoproteins containing 2-9 immunoglobulin-like C2-type structural domains and bind to the lymphocyte function-associated antigen-1 (LFA-1) protein. ICAM3 is abundantly and constitutively expressed in all leukocytes and is probably the most important ligand for LFA-1 in initiating immune responses. In recent years, more and more studies have focused on ICAM3 and found that it is closely related to the pathogenesis of various diseases. Here, we summarize the genomic localization, protein structure, and basic functions of ICAM3, and discuss the research progress of ICAM3 in mediating immune cell function and other diseases. Further, we describe the regulatory role of ICAM3 on the progression of different types of malignant cancers and the associated signaling pathways. Our work assesses the feasibility of ICAM3 as a molecular marker for the diagnosis of human diseases and cancers, which may provide new targets for treating related diseases and cancers. As a typical transmembrane protein, we expect to find or synthesize specific small molecule inhibitors for the treatment of clinically relevant diseases.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 5","pages":"1563-1574"},"PeriodicalIF":3.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WTAP-Mediated N6-Methyladenosine Modification Promotes Gastric Cancer Progression by Regulating MAP2K6 Expression.","authors":"Shuangshuang Han, Haibin Jiang, Jia Wang, Chao Li, Ting Liu, Mingda Xuan, Bo Tian, Yi Si, Hongyan Zhao, Yunxia Zhao, Zhenlong Zhu, Weifang Yu, Lihong Wang","doi":"10.7150/jca.98559","DOIUrl":"10.7150/jca.98559","url":null,"abstract":"<p><p>Wilms tumor 1 associated protein (WTAP) is a key RNA N6-methyladenosine (m⁶A) methylase, which is involved in gastric cancer (GC) development, but its pathogenic mechanism is not clear. This study aims to thoroughly explore the underlying molecular mechanism of WTAP-mediated m⁶A modification in GC pathogenesis. qRT-PCR and immunohistochemistry showed that significantly elevated WTAP expression in GC tissues and is related to advanced age, poorly differentiation, lymph node metastasis and high TNM stage. Overexpression and knockdown of WTAP could promote or inhibit the proliferation, migration and invasion of GC cells <i>in vitro</i>, furthermore, suppression of WTAP expression impeded the growth of xenograft tumors <i>in vivo.</i> Utilizing RNA sequencing, methylated RNA immunoprecipitation (MeRIP) sequencing and bioinformatics analysis, we identified MAP2K6 as direct downstream target of WTAP with m⁶A modification in GC. The interaction between WTAP and MAP2K6 was confirmed by MeRIP-qPCR, luciferase reporter assay, Co-IF and bioinformatics prediction. Immunofluorescence and rescue studies were performed to verify WTAP-mediated m⁶A modification promotes the proliferation, migration, and invasion of GC cells by positively regulating the target gene MAP2K6. This underscores the potential therapeutic significance of targeting the WTAP-MAP2K6 axis in combating GC occurrence and progression.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 5","pages":"1420-1437"},"PeriodicalIF":3.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of Single-Cell and Bulk Transcriptomes to Identify a Poor Prognostic Tumor Subgroup to Predict the Prognosis of Patients with Early-stage Lung Adenocarcinoma.","authors":"Zijian Shi, Linchuang Jia, Baichuan Wang, Shuo Wang, Long He, Yingxi Li, Guixin Wang, Wenbin Song, Xianneng He, Zhaoyi Liu, Cangchang Shi, Yao Tian, Keyun Zhu","doi":"10.7150/jca.105926","DOIUrl":"10.7150/jca.105926","url":null,"abstract":"<p><p><b>Background:</b> Single-cell RNA sequencing (scRNA-seq) has emerged as a pivotal technology for investigating novel therapeutic targets in cancer. Despite its significance, there remains a scarcity of studies utilizing this technology to address treatment strategies specifically tailored for early-stage lung adenocarcinoma (LUAD). Consequently, this study aimed to investigate the tumor microenvironment (TME) characteristics and develop a prognostic model for early-stage LUAD. <b>Methods:</b> The markers identifying cell types were obtained from the CellMarker database and published research. The SCEVAN package was employed for identifying malignant lung epithelial cells. Single-cell downstream analyses were conducted using the SCP package, encompassing gene set enrichment analysis, enrichment analysis, pseudotime trajectory analysis, and differential expression analysis. Calibration curves, receiver operating characteristic curves, and decision curve analysis were employed to assess the performance of the prognostic model for LUAD. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot, cell transfection, cell proliferation, and cell invasion assays were performed to validate the expression and biological function. <b>Results:</b> Seven cell types were distinguished in the scRNA-seq dataset through the utilization of cell markers documented in published literature. Four subpopulations of early-stage LUAD tumor cells exhibited a high degree of heterogeneity. The prognostic model constructed by <i>PERP</i> and <i>KRT8</i> showed a great prediction for distinguishing the early-stage LUAD and normal tissues. The validation of <i>PERP</i> and <i>KRT8</i> expression levels was carried out through both RT-qPCR and western blot analyses. Eventually, <i>in vitro</i> experiments, including CCK8, colony formation, EdU, and transwell assays, confirmed that <i>KRT8</i> and <i>PERP</i> could promote LUAD cell proliferation and migration. <b>Conclusions:</b> Our study provided a comprehensive characterization of the TME in LUAD through integrative single-cell and bulk transcriptomic analyses. We identified dynamic transitions from normal epithelial cells to tumor cells, revealing the heterogeneity and evolution of malignant LUAD cells. The novel prognostic model based on KRT8 and PERP demonstrated robust predictive performance, offering a promising tool for early-stage LUAD risk stratification. Functional experiments further confirmed that KRT8 and PERP promote tumor proliferation and migration, providing new insights into their roles as therapeutic targets.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 4","pages":"1397-1412"},"PeriodicalIF":3.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors Affecting Delayed Recovery from Neutropenia in Patients with Pancreatic Cancer Receiving Gemcitabine plus Nab-Paclitaxel.","authors":"Naoko Yoshida, Shungo Imai, Kazuyoshi Kawakami, Takashi Yokokawa, Masashi Nakamura, Takeshi Aoyama, Hisanori Shimizu, Ryoichi Naito, Minori Teramae, Masami Tsuchiya, Hayato Kizaki, Masato Ozaka, Naoki Sasahira, Masakazu Yamaguchi, Satoko Hori","doi":"10.7150/jca.107359","DOIUrl":"10.7150/jca.107359","url":null,"abstract":"<p><p><b>Background:</b> Many studies have identified risk factors for neutropenia associated with various chemotherapies, including gemcitabine plus nab-paclitaxel (GnP). However, few studies have focused on the delayed recovery from neutropenia, which frequently leads to treatment discontinuation. We aimed to examine whether the risk factors for neutropenia affect delayed recovery following development. <b>Material and Methods:</b> Data were collected from patients with pancreatic cancer who received GnP therapy between December 2014 and March 2019 at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. In the present study, we investigated the following: (1) risk factors for grade 3 or higher neutropenia and (2) factors affecting delayed recovery in patients who developed neutropenia in (1). <b>Results:</b> Of the 638 patients who underwent GnP therapy, 364 developed neutropenia and 29 experienced delayed recovery. Most patients with delayed recovery experienced neutropenia on day 8 of the first course; therefore, we focused on this group. Among the 111 patients who developed neutropenia on day 8 of the first course, 22 experienced delayed recovery after excluding those who received granulocyte-colony stimulating factor. Low baseline neutrophil, platelet, and red blood cell counts were identified as risk factors for neutropenia. Although multivariate analysis could not be conducted due to the limited number of patients, these three factors were also associated with delayed recovery. <b>Conclusion:</b> Low neutrophil, platelet, and red blood cell counts at baseline were identified as risk factors for neutropenia and affecting delayed recovery.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 5","pages":"1413-1419"},"PeriodicalIF":3.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EFHD1 Activates SIK3 to Limit Colorectal Cancer Initiation and Progression via the Hippo Pathway.","authors":"Qionghui Huang, Xiaoyan Tang, Caiyan Gan, Qiaoting Deng, Shaobin Zhi, Qingyan Huang, Xiaoqi Zheng, Xueqiong Li, Zengfeng Pan, Mingfeng Huang","doi":"10.7150/jca.103229","DOIUrl":"10.7150/jca.103229","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is one of the most commonly diagnosed cancers, with high rates of metastasis and lethality. EF-hand domain-containing protein D1 (EFHD1) and salt-inducible kinase 3 (SIK3) have been studied in several cancer types. Aberrant expression of EFHD1 and SIK3 has been observed in CRC, but little research has addressed their regulatory abilities and signaling pathways. In this study, we aimed to explore the efficacy of EFHD1 in inhibiting CRC proliferation and metastasis and to elucidate the underlying mechanisms involved in the upregulation of SIK3 expression. Cell viability, colony formation, wound healing, Transwell assay, orthotopic xenograft, and pulmonary metastasis mouse models were used to detect the antiproliferative and anti-metastatic effects of EFHD1 against CRC <i>in vitro</i> and <i>in vivo</i>. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to determine EFHD1 and SIK3 expression in CRC. The regulatory roles of EFHD1 and SIK3 in mediating anti-metastatic effects in CRC were measured using western blotting, immunohistochemical, and immunofluorescence analyses. The results showed that EFHD1 expression was significantly repressed in the clinical CRC samples. EFHD1 markedly suppressed cell proliferation, migration, and invasion <i>in vitro</i> and inhibited tumor growth and metastasis <i>in vivo</i>. Analysis of the GEPIA database revealed that EFHD1 expression positively correlated with SIK3 expression. SIK3 overexpression inhibited the migration of CRC cells, and SIK3 knockdown partially eliminated the inhibitory effects of EFHD1 on CRC metastasis. EFHD1 exerted anti-metastatic effects against CRC via upregulating SIK3 and inhibiting epithelial-mesenchymal transition (EMT) processing through modulating the Hippo signaling pathway. Collectively, these findings identify EFHD1 as a potent SIK3 agonist and highlight the EFHD1-SIK3 axis as a key modulator of the Hippo signaling pathway in CRC. EFHD1 serves as a novel regulator and is worthy of further development as a novel therapeutic target in CRC.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 4","pages":"1348-1362"},"PeriodicalIF":3.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}