Cancer Medicine最新文献

{"title":"Biological Activity of Biomarkers Associated With Metastasis in Osteosarcoma Cell Lines","authors":"Nidia Ednita Beltrán-Hernández, Luis Cardenas, Verónica Jimenez-Jacinto, Leticia Vega-Alvarado, Heriberto Manuel Rivera","doi":"10.1002/cam4.70391","DOIUrl":"https://doi.org/10.1002/cam4.70391","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Osteosarcoma, a highly aggressive bone cancer primarily affecting children and young adults, remains a significant challenge in clinical oncology. Metastasis stands as the primary cause of mortality in osteosarcoma patients. However, the mechanisms driving this process remain incompletely understood. Clarifying the molecular pathways involved in metastasis is essential for enhancing patient prognoses and facilitating the development of targeted therapeutic strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>RNA sequencing (RNA-Seq) analysis was employed to compare three conditions, hFOB1.19 versus Saos-2, hFOB1.19 versus SJSA-1, and Saos-2 versus SJSA-1, involving non-cancer osteoblasts (hFOB1.19) and highly metastatic osteosarcoma cell lines (Saos-2 and SJSA-1). Additionally, ENA datasets of RNA-Seq from osteosarcoma biopsies were included. Differentially expressed genes (DEGs) were identified and analyzed through enrichment pathway analysis and protein–protein interaction (PPI) networks. Additionally, for gene candidates, a biochemical evaluation was performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DEGs associated with biological functions pertinent to migration, invasion, and metastasis in osteosarcoma were identified. Notably, matrix metalloproteinase-2 (MMP-2) emerged as a promising candidate. Both canonical or full-length (FL-<i>mmp-2</i>) and N-terminal truncated (NTT-<i>mmp-2</i>) isoforms were discerned in biopsies. Moreover, MMP-2's activity was characterized in cell lines. Additionally, mRNA expression of voltage-gated sodium channels (Na<sub>V</sub>s) and voltage-gated potassium channels (K<sub>V</sub>s) was detected, and their functional expression was validated using patch clamp techniques. Evaluation of cell line migration and invasion capacities revealed their reduction in the presence of ion channel blockers (TTX and TEA) and MMP inhibitor (GM6001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The gene functional enrichment analysis of DEGs enabled the identification of interaction networks in osteosarcoma, thereby revealing potential biomarkers. Moreover, the elucidated co-participation of TTX-sensitive Na<sub>V</sub>s and MMP-2 in facilitating migration and invasion suggests their suitability as novel prognostic biomarkers for osteosarcoma. Additionally, this study introduces a model delineating the potential interaction mechanism among ion channels, MMP-2, and other crucial factors in the metastatic cascade of osteosarcoma.</p>\u0000 </section>\u0000 </d","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70391","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perioperative Trends in Distress Among Cancer Patients: A Systematic Review and Meta-Analysis","authors":"Dana G. Rowe,&nbsp;Ellen O'Callaghan,&nbsp;Seeley Yoo,&nbsp;Juliet C. Dalton,&nbsp;Joshua Woo,&nbsp;Edwin Owolo,&nbsp;Tara Dalton,&nbsp;Margaret O. Johnson,&nbsp;Andrea N. Goodwin,&nbsp;Kerri-Anne Crowell,&nbsp;Samantha Kaplan,&nbsp;Melissa M. Erickson,&nbsp;C. Rory Goodwin","doi":"10.1002/cam4.70456","DOIUrl":"https://doi.org/10.1002/cam4.70456","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Distress is common among cancer patients, especially those undergoing surgery. However, no study has systematically analyzed distress trends in this population. The purpose of this study was to systematically review perioperative rates of distress, as well as differences across cancer types, in cancer patients undergoing surgical intervention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic review was conducted using PubMed, EMBASE, Scopus, and APA PsycINFO (searched until July 17, 2023). Included studies were clinical studies of cancer patients undergoing surgery reporting distress measured by the National Comprehensive Cancer Network (NCCN) distress thermometer (DT). Data on study and patient characteristics, and preoperative and postoperative distress rates were extracted. Results were pooled, and overall distress rates were calculated as weighted means. Subanalysis by cancer type was performed. Three meta-analyses were conducted: (1) preoperative distress, (2) postoperative distress, and (3) change in distress.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fifty-seven studies including 13,410 cancer patients were reviewed. Most patients were female (67.4%), White (77.8%), and married/partnered (72.2%), with an average age of 59.2 years. The most common cancers were breast (14 studies), brain (8), and colorectal (7). Weighted mean pre- and postoperative distress scores were 5.1 and 4.5, respectively. Distress remained high through 30 days postoperatively, then declined thereafter. Brain cancer patients reported the highest postoperative distress (5.1), followed by breast cancer patients (4.9).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The perioperative phase is a critical period of elevated distress in cancer patients. Preoperatively, patients experience moderate to severe levels of distress, which persist throughout the early postoperative phase, gradually declining from the 1-month postoperative mark onwards.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70456","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Provincial Variation in Adherence to Breast Cancer Screening in Canada: Evidence From the Canadian Partnership for Tomorrow's Health","authors":"M. Darvishian,&nbsp;A. Moustaqim-Barrette,&nbsp;P. Awadalla,&nbsp;P. Bhatti,&nbsp;P. Broet,&nbsp;R. A. Murphy,&nbsp;K. Skead,&nbsp;R. Urquhart,&nbsp;J. Vena,&nbsp;T. J. B. Dummer","doi":"10.1002/cam4.70543","DOIUrl":"https://doi.org/10.1002/cam4.70543","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Breast cancer is the most commonly diagnosed cancer among women in Canada. Screening is effective in reducing breast cancer mortality through early cancer detection. However, data on individual social and medical characteristics contributing to variation in adherence to screening is limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using multivariable logistic regression, we analyzed self-reported questions on engagement in screening mammography from five regions of the Canadian Partnership for Tomorrow's Health (CanPath), including the BC Generations Project (BCGP), Alberta's Tomorrow Project (ATP), the Ontario Health Study (OHS), Quebec's CARTaGENE, and the Atlantic Partnership for Tomorrow's Health Study (Atlantic PATH).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study population included 79,986 and 46,907 individuals aged 50–74 and 40–49 years at study enrollment, respectively. Most participants self-reported undergoing screening mammography less than 2 years from study enrollment, ranging from 77.8% in OHS to 86.3% in BCGP. Factors significantly associated with a lower odd of ever undergoing screening mammography were lower household income, being single/never married, current daily smoking, poor self-perceived health, no history of breast feeding, and ≥ 24 months since last routine medical check-up by a doctor or nurse. Among women aged 40–49 years with a first-degree family history of breast cancer (<i>N</i> = 4212 [8.9%]), the likelihood of ever being screened varied by region and was significantly lower among individuals with post menopause and more than 12 months since last medical check-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Factors associated with screening adherence that were identified in this study namely household income, self-perceived health, and routine medical check-ups should be considered as potential factors for targeting undeserved communities and increasing engagement in screening at both provincial and national levels. The observed variation in mammography among women aged 40 to 49 years with family history of breast cancer, may inform the current guidelines for potential benefits of early screening initiation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70543","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patterns of Care and Outcomes Among Women With Locally Advanced Cervical Cancer Treated With Curative Intent at a Tertiary Center in South Africa","authors":"Juliet Maina,&nbsp;Katie E. Lichter,&nbsp;Elana T. Benishay,&nbsp;Jessica George,&nbsp;Michelle Henry,&nbsp;Nazia Fakie,&nbsp;Surbhi Grover","doi":"10.1002/cam4.70712","DOIUrl":"https://doi.org/10.1002/cam4.70712","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Cervical cancer is the leading cause of cancer-related deaths for women in South Africa. The standard of care treatment for locally advanced cervical cancer (LACC) is external beam radiation followed by brachytherapy with concurrent platinum-based chemotherapy. There exists a paucity of data regarding the treatment regimens received by women with LACC in South Africa. The aim of this study is to assess the patterns of care and survival for patients with LACC treated with curative intent at a tertiary care center in South Africa.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This is a retrospective review of cervical cancer patients with histologically confirmed LACC (stage IB2—IVA) who underwent radiation with curative intent at Groote Schuur Hospital in Cape Town, South Africa between July 2013 and July 2018. Overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan–Meier method. Cox proportional hazards modeling analyzed patient and treatment factor associations with survival. Logistic regression modeling was performed to assess factors associated with the receipt of chemotherapy and baseline hemoglobin.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 278 patients, 28.4% (<i>n</i> = 79) of women had co-infection with HIV, and 64.8% (<i>n</i> = 180) received chemoradiation. Regardless of HIV status, patients who received chemoradiation had improved 2-year OS (87.4% vs. 52.8%, <i>p</i> &lt; 0.001) and DFS (80.2% vs. 58.3%, <i>p</i> &lt; 0.001) compared to those receiving radiation alone. Factors associated with improved OS were receipt of chemotherapy (HR 0.32, <i>p</i> = 0.005) and higher baseline hemoglobin (HR 0.86, <i>p</i> = 0.018). Upon multivariate logistic regression, adjusting for age, stage, and HIV status, patients with stage III/IV disease were less likely to receive chemotherapy (HR 48.17, <i>p</i> &lt; 0.001) and were less likely to have hemoglobin ≥ 10 g/dL (HR 0.20, <i>p</i> &lt; 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Addition of chemotherapy to standard radiation improved OS in women with LACC, regardless of HIV status. Our findings add to a body of literature highlighting the importance of providing concurrent chemoradiotherapy to all patients with LACC, including persons living with HIV and those with stage III/IV disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70712","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of High lncRNA Expression on Clinicopathological Characteristics and Prognosis of Endometrial Cancer Patients: A Meta-Analysis","authors":"Xiaotong Zhao,&nbsp;Ziling Yang,&nbsp;Tianjiao Zheng,&nbsp;Mengyao Zeng,&nbsp;Xiaowen Lin,&nbsp;Huixin Chen,&nbsp;Weiqin Zheng,&nbsp;Sizheng Peng,&nbsp;Shibo Li,&nbsp;Tao Song,&nbsp;Yuhui Sun","doi":"10.1002/cam4.70755","DOIUrl":"https://doi.org/10.1002/cam4.70755","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Backgrounds</h3>\u0000 \u0000 <p>A growing number of systematic bioinformatics analyses were conducted to investigate the mechanism of interaction between long non-coding RNA (lncRNA) and endometrial carcinoma (EC) to predict the prognosis. However, there is no evidence-based evidence that abnormal lncRNA expression is strongly associated with the pathological characteristics and prognosis of EC patients. In this meta-analysis, we systematically evaluated the relationship between upregulated lncRNA expression levels and clinicopathological features, five-year survival rate, and progression-free survival (PFS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic search was performed across seven reputable databases, namely the China National Knowledge Infrastructure, Wanfang, Wipu, PubMed, Web of Science, Cochrane Library, and Embase, encompassing the period from the inception of each database until November 27, 2022. Heterogeneity among the studies was assessed through the application of Cochran's Q and <i>I</i>² statistics. All statistical analyses were conducted using Stata 14.0 software.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This study encompassed 30 clinical studies, involving a total of 2469 EC patients, and examined the expression of 24 lncRNAs, which were upregulated in EC samples. EC patients with higher expression of lncRNAs showed a later FIGO stage (OR = 1.94, 95% CI: 1.29 ~ 2.91), a poorer histological grade (OR = 3.40, 95% CI: 2.51 ~ 4.60), earlier deep myometrial invasion (OR = 2.57, 95% CI: 1.94 ~ 3.41), a higher likelihood of lymphatic vascular space infiltration (OR = 2.86, 95% CI: 1.15 ~ 7.14), an increased propensity for lymph node metastasis (OR = 2.89, 95% CI: 1.82 ~ 4.60), and a greater likelihood of distant metastasis (OR = 2.39, 95% CI: 1.33 ~ 4.30). All of these were statistically significant (<i>p</i> &lt; 0.05). Furthermore, EC patients with a higher expression level of lncRNAs were significantly associated with five-year survival (<i>p</i> &lt; 0.05) and PFS (<i>p</i> &lt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>High expression levels of upregulated lncRNAs in EC patients are associated with unfavorable clinicopathological features, a poor five-year survival rate, and PFS. It serves as a detrimental prognostic factor and might be a biomarker and therapeutic target for EC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70755","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP5 Promotes Head and Neck Squamous Cell Carcinoma Progression via mTOR Signaling Pathway","authors":"Ni Xiong,&nbsp;Yue Wang,&nbsp;Junhong Jiang","doi":"10.1002/cam4.70752","DOIUrl":"https://doi.org/10.1002/cam4.70752","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive malignancy characterized by limited prognostic markers and treatment options, contributing to high mortality rates. While Ubiquitin-specific peptidase 5 (USP5) has been implicated in various cancers, its role in HNSCC remains poorly understood.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Aims&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study aims to investigate the role of USP5 in the progression of HNSCC and explore its potential as both a prognostic biomarker and a therapeutic target.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Materials &amp; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This work utilized single-cell transcriptomic analysis with the Scissor algorithm to identify distinct epithelial subpopulations, particularly focusing on the Stress subpopulation that exhibited significant upregulation of USP5. Validation was conducted using tissue microarray (TMA) analysis and immunohistochemistry (IHC) to compare USP5 expression levels in HNSCC tissues versus adjacent normal tissues. Furthermore, RNA interference (RNAi) experiments were performed to knock down USP5 expression, assessing its effects on tumor cell behavior, including proliferation, migration, and invasion, as well as the regulation of mTORC1 and NF-κB signaling pathways.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study revealed that the Stress subpopulation, characterized by USP5 upregulation, was associated with enhanced tumor cell proliferation, migration, and invasion. TMA and IHC analyses confirmed that USP5 expression was significantly higher in HNSCC tissues compared to normal tissues, correlating with poor patient prognosis. Additionally, RNAi-mediated knockdown of USP5 led to reduced tumor cell activities and downregulation of the mTORC1 and NF-κB signaling pathways.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Discussion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The findings suggest that USP5 plays a critical role in driving HNSCC progression. Its overexpression in aggressive tumor subpopulations and association with poor clinical outcomes highlight its potential utility as both a prognostic biomarker and a therapeutic target. The observed effects on cell behavior and oncogenic signaling pathways provide mechanistic insights into how USP5 for HNSCC therapy.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study establishes USP5 as a key driver of HNSCC progression, underscoring its p","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70752","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143594896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arid4a Suppresses Breast Tumor Metastasis by Enhancing MTSS1 Expression via mRNA Stability","authors":"Pengfei Wan,&nbsp;Dandan Zhang,&nbsp;Xueting Liu,&nbsp;Wenbao Lu","doi":"10.1002/cam4.70732","DOIUrl":"https://doi.org/10.1002/cam4.70732","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Tumor metastasis is one of the main causes of death in cancer patients; however, the mechanism controlling metastasis is unclear. The posttranscriptional regulation of metastasis-related genes mediated by AT-rich interactive domain-containing protein 4A (Arid4a), an RNA-binding protein (RBP), has not been elucidated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Bioinformatic analysis, qRT–PCR, immunohistochemistry, and immunoblotting were employed to determine the expression of Arid4a in breast tumor tissues and its association with the survival of cancer patients. In vitro and in vivo cellular experiments were used to assess the function of Arid4a in breast tumor metastasis. PCR array, RNA immunoprecipitation (RIP), luciferase, mRNA stability, RIP-ChIP, and EMSA were conducted to elucidate the potential mechanism of Arid4a.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Reduced expression of Arid4a in breast tumor samples was detected via bioinformatic analyses and experimental methods. Low Arid4a expression was significantly correlated with poor prognosis in breast cancer patients. Gain-of-function and silencing experiments confirmed the inhibitory effect of Arid4a on tumor metastasis in vitro and in vivo. Mechanistically, Arid4a preferentially stabilizes metastasis–suppressing transcripts, including <i>metastasis suppressor 1</i> (<i>MTSS1</i>), <i>tissue inhibitor of metalloproteinase 2</i> (<i>TIMP2</i>), <i>retinoblastoma 1</i> (<i>Rb1</i>), and <i>phosphatase and tensin homolog</i> (<i>PTEN</i>), through binding to a conserved structural RNA element localized in the 3′ untranslated region (3′UTR). The Arid domain of Arid4a is required for its mRNA stabilization and metastasis inhibition. Notably, the expression of Arid4a and metastasis-suppressing genes was positively correlated in human breast tumor tissues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Arid4a was confirmed to suppress breast tumor metastasis progression by stabilizing the transcripts of tumor metastasis–suppressing genes, suggesting that Arid4a might be a potential therapeutic target for breast cancer treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70732","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143594897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PRR11 Promotes Bladder Cancer Growth and Metastasis by Facilitating G1/S Progression and Epithelial-Mesenchymal Transition","authors":"Lu Wang,&nbsp;Zengshun Kou,&nbsp;Jiaxi Zhu,&nbsp;Xiu Zhu,&nbsp;Lei Gao,&nbsp;Hai Zhu","doi":"10.1002/cam4.70749","DOIUrl":"https://doi.org/10.1002/cam4.70749","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although Proline-rich Protein 11 (PRR11) abnormalities are closely associated with carcinogenesis, the precise mechanism of bladder cancer remains unclear. Here, we sought to elucidate the molecular mechanisms of PRR11 in bladder cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed differential expression analysis of PRR11 from the TCGA and GEO databases, followed by validation with clinical samples. Survival analysis was employed to assess the correlation between PRR11 and patient prognosis. The effects of PRR11 on bladder cancer cells were examined through both in vitro and in vivo experiments. Additionally, Gene Set Enrichment Analysis (GSEA) was used to predict the downstream pathways associated with PRR11, which were further validated through subsequent experiments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PRR11 is upregulated in bladder cancer and could lead to poor prognosis. In vitro, PRR11 promoted tumor cell proliferation; in vivo, it promoted subcutaneous tumor growth. PRR11 knockdown inhibited its oncogenic function. On the molecular level, PRR11 promotes tumor metastasis by inducing Epithelial-mesenchymal Transition (EMT). GSEA suggests that PRR11 is strongly linked to the cell cycle, and silencing of PRR11 can achieve anti-tumor effects by inhibiting CCNE and blocking the G1/S phase transition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study demonstrates that silencing PRR11 can arrest the malignant progression of bladder cancer by inhibiting EMT and blocking the G1/S transition. Targeting PRR11 may provide new insights for targeting cell cycle therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70749","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chidamide in Combination With DCAG With or Without Venetoclax for Relapsed/Refractory Acute Myeloid Leukemia","authors":"Qingyang Liu,&nbsp;Xiawei Zhang,&nbsp;Lei Lv,&nbsp;Linming Xu,&nbsp;Yu Jing,&nbsp;Wenjing Gao,&nbsp;Lili Wang,&nbsp;Liping Dou","doi":"10.1002/cam4.70734","DOIUrl":"https://doi.org/10.1002/cam4.70734","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Currently, there are only a few avaailable treatment options for patients with relapsed and refractory acute myeloid leukemia (R/R AML).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a single-center, phase 1 prospective study (ChiCTR2200065634) to evaluate the efficacy and safety of chidamide, demethylating drugs (azacitidine), cytarabine, aclacinomycin, and G-CSF plus venetoclax (CDCAG-VEN) in patients with R/R AML. The previous CDCAG regimen was used as a historical control to compare its efficacy and safety. Thirty and 22 patients received one course of CDCAG with or without a 14-day course of venetoclax, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The overall response rate (ORR) was significantly higher in the CDCAG-VEN group than in the CDCAG-treated group (78.6% vs. 45.5%; <i>p</i> = 0.015), and the CDCAG-VEN group achieved a better trend of measurable residual disease-negative response (61.1% vs. 22.2%, <i>p</i> = 0.134). Compared with the CDCAG group, the CDCAG-VEN group exhibited significantly better 1-year overall survival (63.3% vs. 35.1%, <i>p</i> = 0.005) and progression-free survival (76.7% vs. 36.0%, <i>p</i> = 0.022). The duration of response was notably better in the CDCAG-VEN group than in the CDCAG group (71.2% vs. 34.3%, <i>p</i> = 0.021) and had a lower cumulative incidence of relapse (22.2% vs. 48.9%, <i>p</i> = 0.095). The neutrophil and platelet recovery times were similar between the CDCAG-VEN and CDCAG groups (neutrophil: 18 days vs. 19 days, <i>p</i> = 0.293; platelet: 18 days vs. 19 days, <i>p</i> = 0.311). The frequencies of adverse events were comparable between both groups, except for a lower incidence of thrombosis in the CDCAG-VEN group (0% vs. 22.7%, <i>p</i> = 0.006).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>In conclusion, venetoclax in combination with CDCAG is an effective and safe treatment regimen for R/R AML, thereby rapidly identifying chemosensitive patients and inducing measurable residual disease-negative remission in a high proportion of patients with R/R AML.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70734","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Prognostic Risk-Scoring Model Based on RAS Gene-Associated Cluster in Pediatric Acute Myeloid Leukemia","authors":"Cai-Ju Luo,&nbsp;Yilimuguli Abudukeremu,&nbsp;Ming-Liang Rao,&nbsp;Dun-Hua Zhou,&nbsp;Jian-Pei Fang,&nbsp;Yang Li,&nbsp;Lu-Hong Xu","doi":"10.1002/cam4.70716","DOIUrl":"https://doi.org/10.1002/cam4.70716","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>With the rapid development of diagnostic techniques and treatment strategies, there are notable improvements in pediatric acute myeloid leukemia (AML) prognosis. Nevertheless, the pathogenesis of AML remains largely unknown. This study aims to investigate the RAS pathway-associated genes based on bioinformatics analysis, and investigate their underlying mechanisms in the initiation and progression of AML.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>The UCSC Xena database was the source of the training set data, while the GSE192638 dataset was the source of the validation set data. Children in the training set were split up into two groups according to RAS pathway-associated genes, and then differentially expressed genes (DEGs) of them were screened. To discover prognosis-related genes and develop a prognostic risk-scoring model, we employed One-way Cox and LASSO regression analysis. The performance of the model was assessed by an independent validation dataset. Survival analysis was performed using the Kaplan-Meier (K-M) curve. Furthermore, we investigated the association between the prognostic risk-scoring model and the correlation between immune infiltration and drug sensitivity. The expression levels of genes associated with reverse transcription-polymerase chain reaction were quantified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We built a prognostic risk-scoring model comprising 26 DEGs. Depending on the risk score, AML patients were split up into two groups: high- and low-risk groups. Notably, compared with the survival time of patients in the high- risk group, that in the low-risk group was substantially prolonged. Univariate (uniCox) as well as multivariate Cox (multiCox) regression analyses were carried out, demonstrating that the risk score emerged as a separate risk factor for prognosis. A nomogram that incorporates clinical factors and prognostic risk scores was proposed to increase the accuracy of survival rates estimation. Subsequent analyses revealed significant connections of the risk score with the immune infiltration and drug sensitivity. The experimental results demonstrated significantly elevated expression levels of GCSAML, MED12L, and TCF4 in AML samples compared to normal samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The developed prognostic risk-scoring model, along with the identified key risk genes, holds promise as candidate prognostic biomarkers and treatment targets for pediatric AML.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70716","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}