European Journal of Cancer最新文献

{"title":"Perspectives on the role of “-Omics” in predicting response to immunotherapy","authors":"Anna Maria Di Giacomo ,&nbsp;Sumit Subudhi ,&nbsp;Wim Vos ,&nbsp;Massimo Andreatta ,&nbsp;Santiago Carmona ,&nbsp;Will McTavish ,&nbsp;Barbara Seliger ,&nbsp;Ramy Ibrahim ,&nbsp;Michael Lahn ,&nbsp;Michael Smith ,&nbsp;Alexander Eggermont ,&nbsp;Bernard A. Fox ,&nbsp;Michele Maio","doi":"10.1016/j.ejca.2025.115393","DOIUrl":"10.1016/j.ejca.2025.115393","url":null,"abstract":"<div><div>The annual Immuno-Oncology “Think Tank” held in October 2023 in Siena reviewed the rapidly evolving systems-biological approaches which are now providing a deeper understanding of tumor and tumor microenvironment heterogeneity. Based on this understanding opportunities for novel therapies may be identified to overcome resistance to immunotherapy. There is increasing evidence that malignant disease processes are not limited to purely intracellular or genetic events but constitute a dynamic interaction between the host and disease. Tumor responses are influenced by many host tissue determinants across different cellular compartments, which can now be investigated by high-throughput molecular profiling technologies, often labelled with a suffix “-omics”. “Omics” together with ever increasing computational power, fast developments in machine learning, and high-resolution detection tools offer an unrivalled opportunity to connect high-dimensional data and create a holistic view of disease processes in cancer. This review describes advances in several state-of-the-art “-omics” approaches with perspectives on how these can be applied to the clinical development of new immunotherapeutic strategies and ultimately adopted in clinical practice.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115393"},"PeriodicalIF":7.6,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Daratumumab for high-risk smoldering multiple myeloma – Are we there yet?","authors":"Bhavesh Mohan Lal,&nbsp;Samer Al Hadidi","doi":"10.1016/j.ejca.2025.115391","DOIUrl":"10.1016/j.ejca.2025.115391","url":null,"abstract":"","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115391"},"PeriodicalIF":7.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence-based virtual staining platform for identifying tumor-associated macrophages from hematoxylin and eosin-stained images","authors":"Arpit Aggarwal ,&nbsp;Mayukhmala Jana ,&nbsp;Amritpal Singh ,&nbsp;Tanmoy Dam ,&nbsp;Himanshu Maurya ,&nbsp;Tilak Pathak ,&nbsp;Sandra Orsulic ,&nbsp;Kailin Yang ,&nbsp;Deborah Chute ,&nbsp;Justin A. Bishop ,&nbsp;Farhoud Faraji ,&nbsp;Wade M. Thorstad ,&nbsp;Shlomo Koyfman ,&nbsp;Scott Steward ,&nbsp;Qiuying Shi ,&nbsp;Vlad Sandulache ,&nbsp;Nabil F. Saba ,&nbsp;James S. Lewis Jr. ,&nbsp;Germán Corredor ,&nbsp;Anant Madabhushi","doi":"10.1016/j.ejca.2025.115390","DOIUrl":"10.1016/j.ejca.2025.115390","url":null,"abstract":"<div><h3>Background</h3><div>Virtual staining is an artificial intelligence-based approach that transforms pathology images between stain types, such as hematoxylin and eosin (H&amp;E) to immunohistochemistry (IHC), providing a tissue-preserving and efficient alternative to traditional IHC staining. However, existing methods for translating H&amp;E to virtual IHC often fail to generate images of sufficient quality for accurately delineating cell nuclei and IHC+ regions. To address these limitations, we introduce VISTA, an artificial intelligence-based virtual staining platform designed to translate H&amp;E into virtual IHC.</div></div><div><h3>Methods</h3><div>We applied VISTA to identify M2-subtype tumor-associated macrophages (M2-TAMs) in H&amp;E images from 968 patients with HPV+ oropharyngeal squamous cell carcinoma across six institutional cohorts. M2-TAMs are a critical component of the tumor microenvironment, and their increased presence has been linked to poor survival. Co-registered H&amp;E and CD163 + IHC tissue microarrays were used to train (D1, N = 102) and test (D2, N = 50) the VISTA platform. M2-TAM density, defined as the ratio of M2-TAMs to total nuclei, was derived from VISTA-generated CD163 + IHC images and evaluated for prognostic significance in additional training (D3, N = 360) and testing (D4, N = 456) cohorts using biopsy or resection H&amp;E whole slide images.</div></div><div><h3>Results</h3><div>High M2-TAM density was associated with worse overall survival in D4 (p = 0.0152, Hazard Ratio=1.63 [1.1–2.42]). VISTA outperformed existing methods, generating higher-quality virtual CD163 + IHC images in D2, with a Structural Similarity Index of 0.72, a Peak Signal-to-Noise Ratio of 21.5, and a Fréchet Inception Distance of 41.4. Additionally, VISTA demonstrated superior performance in segmenting M2-TAMs in D2 (Dice=0.74).</div></div><div><h3>Conclusion</h3><div>These findings establish VISTA as a computational platform for generating virtual IHC and facilitating the discovery of novel biomarkers from H&amp;E images.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115390"},"PeriodicalIF":7.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between premature menopause and the risk of biliary tract cancer: A nationwide cohort study","authors":"Chi Hoon Maeng ,&nbsp;Kyungdo Han ,&nbsp;Jung Yong Hong ,&nbsp;Joo-Hyun Park","doi":"10.1016/j.ejca.2025.115387","DOIUrl":"10.1016/j.ejca.2025.115387","url":null,"abstract":"<div><h3>Introduction</h3><div>Recent studies indicate a potential link between female reproductive factors and the risk of biliary tract cancer (BTC). However, this association remains controversial due to conflicting results, highlighting the need for further investigation into hormonal influences on BTC development.</div></div><div><h3>Methods</h3><div>We conducted a nationwide cohort study using data from the Korean National Health Insurance System, following 1059,533 menopausal women aged 40–69 years (median follow-up: 9.3 years). Cox proportional hazards regression was applied to assess the risk of cholangiocarcinoma (CCA) and gallbladder cancer (GBC) in relation to reproductive factors, particularly premature menopause (before age 40) and total reproductive period (time from menarche to menopause). The primary outcome was the incidence of BTC, specifically CCA and GBC.</div></div><div><h3>Results</h3><div>During 9.87 million person-years of follow-up, 4198 women (0.40 %) were diagnosed with BTC. Premature menopause was associated with a significant increase in risk for both CCA (adjusted HR 1.29, 95 % CI: 1.01–1.64) and GBC (adjusted HR 1.42, 95 % CI: 1.03–1.97). A shorter total reproductive period (&lt;30 years) was associated with a higher risk of BTC, with an adjusted HR of 1.10 (95 % CI: 0.99–1.21) for CCA and 1.15 (95 % CI: 1.01–1.33) for GBC. Other female reproductive factors assessed showed no significant associations.</div></div><div><h3>Conclusions</h3><div>Premature menopause is associated with an increased risk of BTC, suggesting reduced lifetime exposure to female hormones as a risk factor. These results highlight the importance of considering reproductive history in identifying high-risk women and may inform targeted screening strategies for early detection.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115387"},"PeriodicalIF":7.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"\"Re-re-treatment?\" Third and fourth courses of BRAF/MEK inhibition in advanced melanoma.","authors":"Michael T O'Brien, Sage Iwamoto, Rizwan Haq, Douglas B Johnson","doi":"10.1016/j.ejca.2025.115378","DOIUrl":"https://doi.org/10.1016/j.ejca.2025.115378","url":null,"abstract":"","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":" ","pages":"115378"},"PeriodicalIF":7.6,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matching-adjusted indirect comparison of endoscopic and craniofacial resection for the treatment of sinonasal cancer invading the skull base","authors":"Florian Chatelet ,&nbsp;Sylvie Chevret ,&nbsp;Alessandro Vinciguerra ,&nbsp;Giacomo Bertazzoni ,&nbsp;Domitille Camous ,&nbsp;Marco Ferrari ,&nbsp;Davide Mattavelli ,&nbsp;Mario Turri-Zanoni ,&nbsp;Alberto Schreiber ,&nbsp;Stefano Taboni ,&nbsp;Vittorio Rampinelli ,&nbsp;Alberto Daniele Arosio ,&nbsp;Cesare Piazza ,&nbsp;Paolo Battaglia ,&nbsp;Maurizio Bignami ,&nbsp;Alberto Deganello ,&nbsp;Paolo Castelnuovo ,&nbsp;Piero Nicolai ,&nbsp;Philippe Herman ,&nbsp;Benjamin Verillaud","doi":"10.1016/j.ejca.2025.115382","DOIUrl":"10.1016/j.ejca.2025.115382","url":null,"abstract":"<div><h3>Aim</h3><div>The aim of this study was to compare the efficacy and safety of endoscopic endonasal approaches (EEA) with craniofacial resection (CFR) for sinonasal cancers invading the skull base, using an unanchored matching-adjusted indirect comparison (MAIC).</div></div><div><h3>Methods</h3><div>A MAIC approach was used to analyse data from two large cohorts: the MUlti-institutional collaborative Study on Endoscopically treated Sinonasal cancers (MUSES) cohort, comprising sinonasal cancer patients treated endoscopically, and a historical CFR cohort reported by Ganly et al. Individual patient data were available only for the first cohort. Patients with olfactory neuroblastomas were excluded. Key prognostic factors were used to match and adjust the two cohorts, minimising selection bias. The primary endpoint was overall survival (OS), with secondary endpoints including recurrence-free survival (RFS), perioperative mortality, complication rates, and resection margins.</div></div><div><h3>Results</h3><div>A total of 724 EEA-treated and 334 CFR-treated patients were included. EEA showed significantly improved OS before (HR= 2.33, 95 % CI= 1.88–2.87) and after MAIC adjustment (HR= 1.93, 95 % CI= 1.60–2.34). Observed RFS was higher in the EEA group (HR= 1.39, 95 % CI = 1.14–1.69) but no longer differed after adjustment (HR= 1.06, 95 % CI= 0.91–1.23). EEA was associated with significantly better Disease Specific Survival (HR= 1.71, 95 % CI = 1.39–2.13), lower perioperative mortality (OR= 8.12, 95 % CI= 3.45–36.7) and fewer complications than CFR (OR= 3.68, 95 % CI= 2.47–5.42).</div></div><div><h3>Conclusion</h3><div>In this MAIC study based on the 2 largest cohorts of sinonasal cancer with skull base invasion, EEA offered comparable oncologic outcomes to CFR with reduced morbidity, supporting it as a valid alternative when performed in expert centres.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115382"},"PeriodicalIF":7.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiomic markers associated with clinical benefit in patients with radiographic progression of advanced uveal melanoma on tebentafusp","authors":"Volkan Beylergil ,&nbsp;Laura Collins ,&nbsp;Lawrence H. Schwartz ,&nbsp;Thomas Eche ,&nbsp;Binsheng Zhao ,&nbsp;Stephane Champiat ,&nbsp;Richard Carvajal ,&nbsp;Shaad E. Abedin ,&nbsp;Laurent Dercle","doi":"10.1016/j.ejca.2025.115386","DOIUrl":"10.1016/j.ejca.2025.115386","url":null,"abstract":"<div><h3>Study aim</h3><div>Tebentafusp, a bispecific fusion protein consisting of affinity-enhanced T cell receptor fused to anti-CD3 effector, has shown overall survival (OS) benefits across all RECIST response categories, including progressive disease (PD). In a phase 2 trial (NCT02570308) for advanced uveal melanoma (mUM), 35 % of PD patients experienced ≥ 0.5 log ctDNA reduction, resulting in a median overall survival (OS) of ∼17 months, compared to ∼8 months in the non-ctDNA reduction group.</div></div><div><h3>Methods</h3><div>A total of 34 of 127 2L+ mUM patients with PD were split into two groups based on absence or presence of ctDNA reduction (≥0.5 log reduction). Lesions from CT and MRI scans were analyzed using radiomics features at baseline and week eight, yielding two machine-learning-derived patient signatures (16 features). Performance of per-patient analysis (n = 32) and per-lesion analysis (n = 148) was assessed using ROC AUC (95 % confidence interval [CI]).</div></div><div><h3>Results</h3><div>In the per-patient analysis, a volumetric signature classified patients into groups with ROC AUC of 0.71 [0.53–0.90] with 63 % specificity and 81 % sensitivity at the optimal threshold (0.57). In the per-lesion analysis, a radiomic signature reached an ROC AUC of 0.70 [0.58–0.81] with 66 % specificity and 74 % sensitivity at the optimal threshold (0.53). Group B had lower baseline tumor lesion volume (ROC AUC=0.65), distinct baseline (ROC AUC=0.66), and change by week eight (ROC AUC=0.66/0.69 on CT/MRI) in tumor heterogeneity.</div></div><div><h3>Conclusion</h3><div>Radiomic analysis accurately predicted ctDNA reduction in PD patients at both the patient and lesion level. The most influential predictor was decreased tumor heterogeneity observed on CT/MRI.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115386"},"PeriodicalIF":7.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue-agnostic target profiles and treatment efficacy in cancer patients: Insights from the C-CAT clinicogenomic repository","authors":"Rui Kitadai ,&nbsp;Yusuke Okuma ,&nbsp;Taro Shibata ,&nbsp;Takashi Kohno ,&nbsp;Takafumi Koyama","doi":"10.1016/j.ejca.2025.115380","DOIUrl":"10.1016/j.ejca.2025.115380","url":null,"abstract":"<div><h3>Purpose</h3><div>Utilizing real-world data from Japan's C-CAT clinicogenomic repository, our study demonstrates a significant shift in cancer management through cancer genomic profiling (CGP) tests. The aim of this study is assessing the prevalence of cross-organ targeted genetic alterations and exploring the differences in treatment responses among cancer patients who underwent CGP tests.</div></div><div><h3>Methods</h3><div>Analyzing data from 60,256 patients in the C-CAT repository, we documented the prevalence of FDA-approved biomarkers, cross-organ genetic alterations, and treatment outcomes for tissue-agnostic therapies from June 2019 to December 2023.</div></div><div><h3>Results</h3><div>Biomarkers including <em>RET</em> rearrangement, <em>BRAF</em>^{<em>V600E</em>} mutation, and <em>NTRK</em> rearrangement showed varied therapeutic responses, underscoring the need for universal CGP testing to optimize patient outcomes. Notably, our findings highlight variations in response across different age groups, suggesting the potential for age-specific treatment strategies. Comparisons with the AACR Project GENIE database revealed broader implications for the global genomic landscape.</div></div><div><h3>Conclusion</h3><div>This study emphasizes the crucial role of clinicogenomic repositories in advancing precision oncology across diverse populations, underscoring the utility of integrating clinical and genomic data in national repositories.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115380"},"PeriodicalIF":7.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patterns of disease dissemination and survival in patients with synchronous and metachronous metastatic pancreatic adenocarcinoma: Nationwide population-based study","authors":"Merlijn U.J.E. Graus ,&nbsp;Aniek E. van Diepen ,&nbsp;Kim Josemanders ,&nbsp;Marc G. Besselink ,&nbsp;Stefan A.W. Bouwense ,&nbsp;Lois A. Daamen ,&nbsp;Ignace H.J.T. de Hingh ,&nbsp;Evelien J.M. de Jong ,&nbsp;Hanneke W.M. van Laarhoven ,&nbsp;Vincent E. de Meijer ,&nbsp;I. Quintus Molenaar ,&nbsp;Martijn W.J. Stommel ,&nbsp;Liselot B.J. Valkenburg-van Iersel ,&nbsp;Johanna W. Wilmink ,&nbsp;Lydia G.M. van der Geest ,&nbsp;Judith de Vos-Geelen ,&nbsp;for the Dutch Pancreatic Cancer Group","doi":"10.1016/j.ejca.2025.115385","DOIUrl":"10.1016/j.ejca.2025.115385","url":null,"abstract":"<div><h3>Aim</h3><div>Despite advances in understanding pancreatic adenocarcinoma, evidence on its metastatic patterns and impact on patient survival remains limited. This study aims to identify patterns of disease dissemination in synchronous versus metachronous metastatic pancreatic adenocarcinoma (mPAC) and their association with overall survival (OS).</div></div><div><h3>Methods</h3><div>Patients diagnosed with synchronous- or metachronous-mPAC were selected from the Netherlands Cancer Registry (2015–2021). Patient, tumor, and treatment characteristics were compared using Chi-squared tests. Survival data, calculated from detection of metastatic disease (OS-M), were analyzed using Kaplan-Meier and Log-rank tests.</div></div><div><h3>Results</h3><div>Overall, 10,788 patients with synchronous- and 508 with metachronous-mPAC were included. Median time to first metastasis in metachronous-mPAC was 13.2 months (IQR 9–23), varying significantly by metastatic site (liver-only 11.5; lung-only 28.0 months). Compared to synchronous-mPAC, patients with metachronous-mPAC had less liver metastases (48 % versus 75 %, p &lt; 0.001), but more lung (29 % versus 21 %, p &lt; 0.001) and peritoneal (35 % versus 25 %, p &lt; 0.001) metastases. Synchronous metastases to liver-only, lung-only, lymph node-only, or multiple sites at first diagnosis had a median OS-M that was (nearly) half compared to metachronous metastases to the same sites. Bone-only or peritoneum-only metastases in synchronous-mPAC showed a median OS-M comparable to metachronous-mPAC.</div></div><div><h3>Conclusion</h3><div>This nationwide population-based study reveals that metachronous-mPAC less commonly presents with liver metastases and more often metastasizes to lung, peritoneum or other atypical sites compared to synchronous-mPAC. These distinct metastatic patterns and their differences in survival may help enhance the prognostic estimation for individual patients from the detection of metastatic disease and warrants further research into the biology underlying metastasis development.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115385"},"PeriodicalIF":7.6,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the clinical impact of differential DNA methylation in PDAC: A systematic review","authors":"Julia Adriana Kasmirski,&nbsp;Raj Roy,&nbsp;Christopher Wu,&nbsp;Lauren Wheeler,&nbsp;K. Kerrick Akinola,&nbsp;Herbert Chen,&nbsp;J. Bart Rose,&nbsp;Changde Cheng,&nbsp;Smita Bhatia,&nbsp;Andrea Gillis","doi":"10.1016/j.ejca.2025.115384","DOIUrl":"10.1016/j.ejca.2025.115384","url":null,"abstract":"<div><h3>Introduction</h3><div>Despite significant efforts to improve clinical outcomes, pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate. The poor prognosis associated with this disease is multifactorial and associated with a highly variable genetic profile associated with its pathogenesis. Epigenetic modifications including DNA methylation further affect the expression of genetic material. However, there is no comprehensive understanding of the clinical impact of DNA methylation in PDAC.</div></div><div><h3>Methods</h3><div>A systematic literature review was registered on the International Prospective Register of Systematic Reviews database (CRD42023451955) and followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. An electronic search was conducted using the following databases: CINAHL Plus, Cochrane Library, Embase, Web of Science, Ovid Medline, and Google Scholar. Inclusion criteria included studies of patients with a PDAC diagnosis and information regarding genes or CpG sites that potentially affect diagnosis, prognosis, or survival of PDAC.</div></div><div><h3>Results</h3><div>The initial search retrieved 2402 articles, and 423 duplicates were excluded. After exclusion criteria was applied, 19 studies were included. The most common genes recorded as affecting tumor pathogenesis were <em>SFRP1</em> (n = 3/19, 15.7 %) and <em>NPTX2</em> (n = 2/19, 10,5 %). Studies indicated that hypermethylation of <em>SFRP1</em> and <em>NPTX2</em> were associated with poor prognosis.</div></div><div><h3>Conclusions</h3><div>PDAC is associated with a range of epigenetic modifications. Methylation of specific genes related to PDAC may influence survival and prognosis and be a therapeutic target. Individual patient epigenetic analysis may be a future direction in directing PDAC treatment and prognosis.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115384"},"PeriodicalIF":7.6,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}