Cancer Medicine最新文献

{"title":"Utility of a Large Series of B-Cell Precursor Acute Lymphoblastic Leukemia Cell Lines as a Model System","authors":"Minori Tamai,&nbsp;Chiaki Komatsu,&nbsp;Keiko Kagami,&nbsp;Shin Kasai,&nbsp;Koshi Akahane,&nbsp;Kumiko Goi,&nbsp;Kanji Sugita,&nbsp;Chihiro Tomoyasu,&nbsp;Toshihiko Imamura,&nbsp;Hiroaki Goto,&nbsp;Takeshi Inukai","doi":"10.1002/cam4.70736","DOIUrl":"https://doi.org/10.1002/cam4.70736","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In B-cell precursor acute lymphoblastic leukemia (BCP-ALL), chromosomal translocations are strongly associated with prognoses. RNA sequencing (RNA-seq) is a powerful technology that reveals a close correlation between types of translocation and patterns of gene expression in clinical samples of BCP-ALL. Cancer cell lines are powerful research tools, and thus, we built a larger series of BCP-ALL cell lines and performed RNA-seq analysis to confirm their utility as a model system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed RNA-seq in a total of 94 BCP-ALL cell lines, including 80 cell lines with 8 representative types of translocations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the UMAP visualization, a close association was confirmed between the types of fusion genes and patterns of gene expression. In the cluster analysis of the gene expression profile, each type of fusion gene showed a clear association with the expression profile in the top 51 variable genes. Of clinical importance, the majority of the top variable genes in the BCP-ALL cell lines also showed a significant association with the types of fusion genes in the clinical samples. When an association of 125 cell cycle-related genes with the percentage of S and G2/M phases in 67 cell lines was evaluated, a significant positive correlation with cell cycle progression was confirmed in 10 cell cycle-related genes (<i>HDAC2</i>, <i>CDC23</i>, <i>YWHAG</i>, <i>MAD2L1</i>, <i>CCNH</i>, <i>ANAPC7</i>, <i>CDC6</i>, <i>ANAPC5</i>, <i>ORC3</i>, and<i>RBX1</i>). Moreover, significant upregulation and downregulation of 40 and 10 genes, respectively, were observed in the cell lines established at relapse compared with those established at diagnosis. Four (<i>SP6</i>, <i>CCNE1</i>, <i>HIST1H2BH</i>, and <i>DECR2</i>) and two (<i>EVI2B</i> and <i>SYN1</i>) of these genes were also significantly higher and lower, respectively, in the clinical samples at relapse than in those at diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Large series of BCP-ALL cell lines is a powerful research tool for studying the mechanisms of leukemogenesis and the disease progression of BCP-ALL.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70736","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521925","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":"Dynamic Monitoring of Circulating Tumor DNA to Predict the Risk of Non In Situ Recurrence of Postoperative Glioma: A Prospective Cohort Study","authors":"Guangzhong Guo,&nbsp;Ziyue Zhang,&nbsp;Jiubing Zhang,&nbsp;Dayang Wang,&nbsp;Sensen Xu,&nbsp;Shuang Wu,&nbsp;Kaiyuan Deng,&nbsp;Yage Bu,&nbsp;Zhiyuan Sheng,&nbsp;Jinliang Yu,&nbsp;Yushuai Gao,&nbsp;Zhaoyue Yan,&nbsp;Ruijiao Zhao,&nbsp;Meiyun Wang,&nbsp;Tianxiao Li,&nbsp;Xingyao Bu","doi":"10.1002/cam4.70733","DOIUrl":"https://doi.org/10.1002/cam4.70733","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Glioma recurrence can be divided into in situ recurrence and non-in situ recurrence, and the mutation evolution of gliomas with different recurrence patterns is still unknown. We used sequential sequencing of circulating tumor DNA (ctDNA) to compare the somatic mutation profile and clonal evolution of gliomas with different recurrence patterns. To investigate the value of ctDNA in predicting early postoperative tumor recurrence and guiding prognosis stratification in patients with glioma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We prospectively recruited 92 patients with near-total resection of gliomas from our center. Two hundred and thirty-four postoperative tissue and Tumor In Situ Fluid (TISF) samples from 69 eligible patients were included in ctDNA analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 69 patients, 37 glioblastoma (GBM) patients experienced recurrence, and the median progression-free survival (mPFS) was not significantly different between the situ recurrence group and the non-in situ recurrence group (8.6 vs. 6.1 months). The ctDNA of recurrent tissue and TISF were significantly consistent. Before and after initial treatment, TISF-ctDNA mutant allele fraction (MAF), subclonal mutation, and alterations in related pathways (lysine degradation and PI3K pathway) were negatively correlated with treatment response and PFS. Among recurrent GBM patients, EGFR mutations were the most common. Mutations related to the RTK-RAS pathway (NF1) were most common in patients with situ recurrent GBM, while mutations in the MUC family and TP53 pathway (MUC16, CHEK2) were prevalent and continuously increased in patients with non-in situ recurrent GBM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In glioma patients undergoing primary surgery, dynamic monitoring of ctDNA and genotyping can be used for early risk stratification, efficacy monitoring, and early recurrence detection, and provide a basis for clinical research to evaluate early therapeutic intervention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70733","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521926","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":"Efficacy of the PanCareFollowUp eHealth Lifestyle Intervention for Survivors of Childhood, Adolescent and Young Adult Cancer","authors":"Selina R. van den Oever,&nbsp;Eline Bouwman,&nbsp;Helena J. H. van der Pal,&nbsp;Philippa C. Steensma,&nbsp;Vera Araujo-Soares,&nbsp;Morven Brown,&nbsp;Tomas Kepak,&nbsp;Katerina Kepakova,&nbsp;Marta Fiocco,&nbsp;Lucy M. M. Fremouw,&nbsp;Maria M. W. Koopman,&nbsp;Raphaële R. L. van Litsenburg,&nbsp;Patrick van der Torre,&nbsp;Joyce Wilbers,&nbsp;Roderick Skinner,&nbsp;Leontien C. M. Kremer,&nbsp;Jacqueline Loonen,&nbsp;Saskia M. F. Pluijm,&nbsp;the PanCareFollowUp consortium","doi":"10.1002/cam4.70694","DOIUrl":"https://doi.org/10.1002/cam4.70694","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>A healthy lifestyle may prevent or mitigate late effects in childhood, adolescent and young adult (CAYA) cancer survivors. To support survivors in adopting healthier behaviours, the PanCareFollowUp (PCFU) Lifestyle intervention was developed, encompassing 4 months of online lifestyle coaching aimed at achieving a personal lifestyle goal. The aims of this study were to (1) determine the efficacy of this intervention on lifestyle outcomes over time and (2) identify predictors for goal achievement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients and Methods</h3>\u0000 \u0000 <p>Fifty-eight survivors were enrolled. Outcomes were assessed at baseline (T0), after 4 months of coaching (T1) and after 4 months of follow-up (T2). The primary outcome included the percentage of survivors successful in achieving and sustaining their goal, whereas secondary outcomes included differences in body mass index (BMI), diet and physical activity. To evaluate the adjusted, longitudinal effects on secondary outcomes, linear mixed models were estimated. Predictors for goal achievement were identified through logistic regression analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At T1 and T2, 68% and 76% of goals were achieved or sustained, respectively. Mean differences between T2 and T0 showed significant improvements in BMI (−0.5 kg/m²), diet (−0.6 points) and physical activity (+7.7 h/week). Estimation of multivariable models also showed positive effects. Participants with a lower BMI and fewer depressive feelings at baseline were more likely to achieve and/or sustain their goals at T2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Findings suggest that the PCFU Lifestyle intervention supports survivors in making lifestyle changes. Results can be used to inform a subsequent randomised intervention study and integrate lifestyle coaching into care.</p>\u0000 \u0000 <p><b>Trial Registration:</b> International Clinical Trial Registry Platform (ICTRP) number: NL8932 (ICTRP Search Portal [who. int]). Registered on 29 September 2020</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70694","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513543","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":"Interventions to Support Transitions in Care Among Patients With Cancer: A Scoping Review","authors":"Negar Rezaei,&nbsp;Jaling Kersen,&nbsp;Abigail Thomas,&nbsp;Stefan Kurbatfinski,&nbsp;Diane Lorenzetti,&nbsp;Khara Marissa Sauro","doi":"10.1002/cam4.70660","DOIUrl":"https://doi.org/10.1002/cam4.70660","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The cancer journey from diagnosis through survivorship is complex and involves care from many healthcare providers across a variety of settings. Navigating the transitions between care providers and settings can be improved through interventions. The objective of this study was to map and characterize evidence on interventions to improve transitions in care among patients with cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>Six databases were searched to identify relevant studies that described or evaluated interventions to support transitions in care for patients with cancer. Data on the interventions, the type of transition in care, type of cancer, and outcomes (including measure of effectiveness) were abstracted. Data were synthesized and analyzed using descriptive statistics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>Of the 38,876 data sources identified, 150 were included. Most included studies were from the United States and were observational studies exploring interventions to facilitate the transition from treatment to survivorship (followed by interventions for the transition from hospital to home) among patients with breast cancer (followed by gastrointestinal cancers, lung cancers, and hematologic cancers). Interventions that were found to be effective were most commonly those that facilitated the transition from diagnosis to treatment and for the transition from hospital to home.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This comprehensive synthesis is an important resource for those trying to improve transitions in care for patients living with and beyond cancer. Despite the large body of evidence identified, gaps remain; there is a paucity of studies exploring transitions in care during cancer treatment and among some cancers (e.g., brain tumors, head and neck, pancreatic).</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70660","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513545","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":"National Survey of Real-World Australian Treatment Patterns for Patients With Very-Early-To Intermediate-Stage Hepatocellular Carcinoma","authors":"Stuart K. Roberts,&nbsp;Ammar Majeed,&nbsp;Kiran Rasaratnam,&nbsp;John K. Olynyk,&nbsp;Nicholas Shackel,&nbsp;Marnie Wood,&nbsp;Simone I. Strasser,&nbsp;Alan Wigg","doi":"10.1002/cam4.70722","DOIUrl":"https://doi.org/10.1002/cam4.70722","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background/Purpose of the Study</h3>\u0000 \u0000 <p>The treatment landscape for very early to intermediate stage hepatocellular carcinoma (HCC) is rapidly evolving, with new data and treatments emerging in recent years. There is a lack of data on current patterns of management for very early to intermediate stage HCC in Australian clinical practice and the role of newly emerging treatment options.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Multidisciplinary specialists involved in HCC management (<i>N</i> = 86) participated in one of six state-based meetings across Australia. Specialists were surveyed on their preferred management approaches at key clinical decision points for four patient case studies ranging from very early to intermediate stage HCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Preferred management strategies for each of the patient case studies were largely consistent with current Australian HCC recommendations in relation to surveillance, diagnosis, and treatment of HCC although the preferred initial treatment selection varied considerably within and between hepatologists and other craft groups. There was, however, growing interest in emerging treatments, including stereotactic ablative body radiotherapy (SABR) for early stage HCC and systemic treatments used as adjuvant therapy or in combination with locoregional therapy in early and intermediate-stage HCC. However, many participants required more data on these treatment modalities before incorporating them into routine clinical practice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The heterogeneity of (very) early to intermediate-stage HCC patients and the increasing number of available treatment options means clinical decision-making, including treatment selection, is becoming more complex and diverse. More data are required to define the role of SABR and systemic therapies in very early to intermediate stage HCC before being adopted as standard of care in Australia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70722","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513544","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":"Data-Driven Molecular Typing: A New Frontier in Esophageal Cancer Management","authors":"Yue Du,&nbsp;Bianli Gu,&nbsp;Linlin Shi,&nbsp;Yong She,&nbsp;Qi Zhao,&nbsp;Shegan Gao","doi":"10.1002/cam4.70730","DOIUrl":"https://doi.org/10.1002/cam4.70730","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Esophageal squamous cell carcinoma (ESCC) is a predominant and highly lethal form of esophageal cancer, with a five-year survival rate below 20%. Despite advancements, most patients are diagnosed at advanced stages, limiting effective treatment options. Multi-omics integration, encompassing somatic genomic alterations, inherited genetic mutations, transcriptomics, proteomics, metabolomics, and single-cell sequencing, has enabled the identification of distinct molecular subtypes of ESCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>This article systematically reviewed the current status of molecular subtyping of ESCC based on big data, summarized unique subtypes with differing treatment responses and prognostic outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>Key findings included subtype-specific genetic mutations, signaling pathway alterations, and metabolomic profiles, which offer novel biomarkers and therapeutic targets. Furthermore, this review discusses the link between molecular subtypes and immunotherapy efficacy, chemotherapy response, and drug development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These insights highlight the potential of omics-based molecular typing to transform ESCC management and facilitate personalized treatment strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70730","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513633","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":"Durvalumab Monotherapy in Complex Advanced Hepatocellular Carcinoma: A Real-World Study of Patients Ineligible for Combination Immunotherapy","authors":"Chihiro Miwa,&nbsp;Sadahisa Ogasawara,&nbsp;Takuya Yonemoto,&nbsp;Sae Yumita,&nbsp;Tomomi Okubo,&nbsp;Miyuki Nakagawa,&nbsp;Keisuke Koroki,&nbsp;Masanori Inoue,&nbsp;Naoya Kanogawa,&nbsp;Masato Nakamura,&nbsp;Takayuki Kondo,&nbsp;Shingo Nakamoto,&nbsp;Norio Itokawa,&nbsp;Masanori Atsukawa,&nbsp;Ei Itobayashi,&nbsp;Naoya Kato","doi":"10.1002/cam4.70642","DOIUrl":"https://doi.org/10.1002/cam4.70642","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Combination immunotherapy is the standard of care for advanced hepatocellular carcinoma (HCC). However, some patients are unsuitable for such treatment. This study investigated the safety and effectiveness of durvalumab monotherapy in a real-world cohort with advanced HCC who were poor candidates for combination immunotherapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively analyzed data from 35 patients with advanced HCC treated with durvalumab monotherapy across three Japanese institutions between January and December 2023. Patients were selected based on their ineligibility for combination immunotherapy or vascular endothelial growth factor inhibiting tyrosine kinase inhibitors (VEGF-TKIs). Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The median age was 71 years, with 51.4% classified as Child–Pugh B or C. Notably, 91.4% of patients were ineligible for the IMbrave150 or HIMALAYA trials. Median PFS was 2.7 months (95% CI: 1.84–6.2) and the median OS was not reached. The ORR and DCR were 2.9% and 51.4%, respectively. Grade ≥ 3 treatment-related AEs (trAEs) occurred in 8.6% of patients, with a discontinuation rate of 11.4% due to AEs. The most common AEs were aspartate aminotransferase (AST) increased (34.3%), hypoalbuminemia (28.6%), and alanine aminotransferase (ALT) increased (25.7%). Immune-mediated AEs (imAEs) affected 14.3% of the patients. The albumin-bilirubin (ALBI) scores showed no significant deterioration in patients without progressive disease (PD) over 12 weeks after treatment initiation (<i>p</i> = 0.771).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Durvalumab monotherapy demonstrated a favorable safety profile and comparable effectiveness to VEGF-TKIs in patients with advanced HCC unsuitable for combination immunotherapy, especially for those with Child–Pugh B status.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70642","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497054","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":"Feature Selection and Network-Driven Analyses to Unveil Common RNA Signatures in Colon and Pancreatic KRAS-Mutant Cancers","authors":"Katia Pane,&nbsp;Mario Zanfardino,&nbsp;Anna Maria Grimaldi,&nbsp;Ilaria Leone,&nbsp;Silvia Nuzzo,&nbsp;Marco Salvatore,&nbsp;Monica Franzese","doi":"10.1002/cam4.70468","DOIUrl":"https://doi.org/10.1002/cam4.70468","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Colon cancer and pancreatic ductal adenocarcinoma are among the most aggressive tumors for which therapeutic options are limited. Both cancers share common features, such as some KRAS pathogenic variants and common epidemiology. The integration of multidimensional datasets by combining machine learning and bioinformatics approaches could provide deeper insights into the intricate KRAS-related networks underlying cancer progression and unveil novel biomarkers and potential therapeutic targets. This study aimed to uncover colon and pancreatic cancers that shared transcriptional changes closely related to KRAS missense mutations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Feature Selection (FS) technique and Qiagen's Ingenuity Pathway Analysis (IPA) were used to combine DNA-Seq and RNA-Seq data from mutant and wild-type (WT) KRAS colon and pancreatic tumor samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>From the FS, we prioritized 70 genes (54 protein-coding genes and 16 ncRNA-coding genes) that were able to discriminate between WT and mutated KRAS patients. These genes were involved in KRAS signaling and other related processes, such as EMT signaling, glycolysis, apical junction, Wnt/beta-catenin signaling, and IL-2/STAT5 signaling. Using IPA, we identified a top-scoring network of 19 upregulated genes in both tumor types stratified into mutant KRAS and WT KRAS samples. For a set of genes, qRT–PCR performed on colon and pancreatic representative cancer cell lines showed concordant expression trends when comparing colon-dominant KRAS mutants versus WT KRAS and dominant pancreatic KRAS mutants versus WT KRAS, as expected according to in silico analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings may provide insight into the common transcriptional signatures potentially underlying colon and pancreatic KRAS-mutant cancers. However, further studies are needed to elucidate the diagnostic and prognostic value of targets identified as common features in our study.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70468","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497056","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 Prognostic Value of Tumor-Associated Neutrophils in Colorectal Cancer: A Systematic Review and Meta-Analysis","authors":"Mengyuan Jiang,&nbsp;Rui Zhang,&nbsp;Min Huang,&nbsp;Jing Yang,&nbsp;Qianqian Liu,&nbsp;Ziru Zhao,&nbsp;Ya Ma,&nbsp;Hongfan Zhao,&nbsp;Min Zhang","doi":"10.1002/cam4.70614","DOIUrl":"https://doi.org/10.1002/cam4.70614","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Tumor-associated neutrophils (TANs) are important components of the colorectal cancer (CRC) microenvironment. However, their role in CRC remains controversial. This study aimed to assess the prognostic value of TANs in patients with CRC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We searched the PubMed, EMBASE, and Cochrane Library databases for eligible studies published until January 9, 2023. The pooled hazard ratios (HRs) and odds ratios (ORs) with their 95% confidence intervals (95% CI) were calculated with a random-effects model to assess survival outcomes and clinicopathological features. Subgroup analyses were further conducted to identify potential sources of heterogeneity. Funnel plots and Egger's test were used to measure publication bias.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 19 studies with 7721 patients were included in this meta-analysis. The pooled analysis indicated that high peritumoral TAN infiltration in CRC tissue was significantly associated with favorable cancer-specific survival (HR = 0.57; 95% CI: 0.38–0.86; <i>p</i> = 0.007), but not with overall survival or disease-free survival. No association between high intratumoral or unclear compartment TAN infiltration and CRC prognosis was found. Subgroup analyses showed that the association between TANs and the prognosis of CRC patients differed according to antibody types, tumor stage, quantitative methods, and follow-up time. High intratumoral TAN infiltration was significantly associated with histology type, whereas high TAN infiltration in an unclear compartment was significantly associated with gender, tumor location, and the primary tumor site.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>High TAN infiltration, especially in the peritumoral compartment, could be a potential prognostic marker in CRC. More high-quality studies are required to explore its specific prognostic value in CRC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70614","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497090","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 highly sensitive screening system to evaluate the reversibility of neuroendocrine prostate cancer to prostate adenocarcinoma","authors":"Tomohiro Fukui,&nbsp;Kosuke Okasho,&nbsp;Yukiko Okuno,&nbsp;Maki Fujiwara,&nbsp;Kensuke Hikami,&nbsp;Arinobu Fukunaga,&nbsp;Takuro Sunada,&nbsp;Yuki Kita,&nbsp;Takayuki Sumiyoshi,&nbsp;Takayuki Goto,&nbsp;Ryoichi Saito,&nbsp;Osamu Ogawa,&nbsp;Takashi Kobayashi,&nbsp;Shusuke Akamatsu","doi":"10.1002/cam4.70047","DOIUrl":"https://doi.org/10.1002/cam4.70047","url":null,"abstract":"&lt;p&gt;Prostate cancer grows in an androgen-dependent manner, and the standard therapy for advanced prostate cancer is endocrine therapy targeting the androgen receptor (AR) signaling pathway. However, with the widespread use of potent next-generation AR signaling inhibitors (ARSIs), the incidence of treatment-related neuroendocrine prostate cancer (t-NEPC), which is completely independent of the AR pathway, is rapidly rising.&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; Unlike its AR-dependent ancestor, t-NEPC remains a poor prognosis cancer, lacking effective treatment options, and thus necessitating the exploration and development of innovative therapies.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Transdifferentiation of prostate adenocarcinoma into neuroendocrine prostate cancer (NEPC) occurs through lineage plasticity.&lt;span&gt;&lt;sup&gt;3-5&lt;/sup&gt;&lt;/span&gt; Lineage plasticity is a biological process that enhances cell survival by enabling adaptation to the environment, avoidance of stress, or tissue repair.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Within cancer, lineage plasticity facilitates the development of therapy resistance in cancer cells by reprogramming into therapy-resistant phenotypes that bypass targeted therapies.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; This phenomenon is especially notable in cancer varieties where there are potent targeted therapies for key growth pathways, such as AR-driven prostate cancer, epidermal growth factor receptor (EGFR)-mutant lung cancer, and BRAF-mutant melanoma.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Recent genomic analyses have revealed several alterations enriched in t-NEPC, with the loss of tumor suppressor genes (&lt;i&gt;TP53&lt;/i&gt; and &lt;i&gt;RB1&lt;/i&gt;) being crucial genomic changes linked to t-NEPC.&lt;span&gt;&lt;sup&gt;3, 6&lt;/sup&gt;&lt;/span&gt; Moreover, epigenetic genes, such as &lt;i&gt;EZH2&lt;/i&gt; and &lt;i&gt;SOX2&lt;/i&gt;, induce neuroendocrine (NE) transdifferentiation.&lt;span&gt;&lt;sup&gt;7, 8&lt;/sup&gt;&lt;/span&gt; A study with gene-engineered mice lacking &lt;i&gt;Pten&lt;/i&gt; and &lt;i&gt;Rb1&lt;/i&gt;, or all three (&lt;i&gt;Pten&lt;/i&gt;, &lt;i&gt;Rb1&lt;/i&gt;, and &lt;i&gt;Trp53&lt;/i&gt;), showed reduced expression of AR and increased expression of NE-related genes, phenocopying human NEPC. Furthermore, using EZH2 inhibitors restored AR expression and sensitivity to antiandrogen therapy.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; These findings suggest that plasticity in t-NEPC is potentially reversible, and regulating cellular lineage could serve as a novel therapeutic strategy. However, EZH2 inhibition did not increase AR expression or activity in organoids from human NEPC.&lt;span&gt;&lt;sup&gt;9&lt;/sup&gt;&lt;/span&gt; To date, the reversibility of lineage plasticity in prostate cancer has not been confirmed in human-derived t-NEPC clinical models.&lt;/p&gt;&lt;p&gt;One major hurdle in NEPC research is the paucity of human-derived t-NEPC cell lines suitable for genetic manipulation or large-scale compound screening. Previously, we created a novel t-NEPC cell line called KUCaP13, derived from a patient-derived xenograft (PDX) and verified its lineage originating from prostate adenocarcinoma.&lt;span&gt;&lt;sup&gt;10&lt;/sup&gt;&lt;/span&gt; The cell line's ","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497138","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}