International Journal of Cancer最新文献

{"title":"Managing hydrocephalus in patients with leptomeningeal disease: A multicenter retrospective analysis.","authors":"Obada T Alhalabi, Lukas Klein, David Wasilewski, Amine Mellal, Carmen Büsken, Clara Buszello, Giulia Cossu, Ilker Y Eyüpoglu, Andreas W Unterberg, Peter Vajkoczy, Gabriele Schackert, Mahmoud Messerer, Martin Misch, Tobias Kessler, Wolfgang Wick, Christine Jungk, Ahmed El Damaty, Sandro M Krieg, Tareq A Juratli, Alexander Younsi","doi":"10.1002/ijc.35505","DOIUrl":"https://doi.org/10.1002/ijc.35505","url":null,"abstract":"<p><p>Leptomeningeal disease (LMD) represents a terminal condition of tumor cell seeding that can cause symptomatic hydrocephalus. With improved survival rates under systemic therapy, the role of cerebrospinal fluid (CSF) drainage through ventriculo-peritoneal shunt (VPS) or Rickham reservoir (RR) placement in LMD patients is gaining more relevance. This study aimed to compare outcomes of both modalities in a multicentric contemporary cohort. A retrospective analysis of medical charts in patients receiving VPS for LMD and malresorptive hydrocephalus in two neurosurgical centers between 2006 and 2021 yielded 64 patients. The most common underlying oncological conditions were breast (n = 32, 49%) and non-small cell lung cancer (NSCLC, n = 16, 25%). The median time between primary and LMD diagnosis was 23.3 months (11.2 to 43.4 months). Symptoms of intracranial hypertension were relieved in 79% of cases (n = 50) after shunting, with 42 (66%) and 32 patients (50%) receiving systemic and intrathecal therapy, respectively. A further multicenter analysis comparing patients receiving VPS with patients receiving RR (with regular tapping) included 155 patients (VPS: n = 80, 52%; RR: n = 75, 48%). Compared to VPS, RRs were associated with a lower surgical revision rate (8% vs. 24%, p = 0.009). There was no difference in median overall survival in VPS patients (118 days) compared to RR patients (80 days, p = 0.180). Given this data showing a short and comparable survival of patients under both modalities with a lower RR complication rate, a rationale for an initial Rickham implantation in LMD patients with hydrocephalus, with later VPS conversion for long-term surviving patients, could be contemplated.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SOX10, MITF, and microRNAs: Decoding their interplay in regulating melanoma plasticity.","authors":"Xin Lai, Chunyan Luan, Zhesi Zhang, Anja Wessely, Markus V Heppt, Carola Berking, Julio Vera","doi":"10.1002/ijc.35499","DOIUrl":"https://doi.org/10.1002/ijc.35499","url":null,"abstract":"<p><p>Recent studies show that the dysregulation of the transcription factor SOX10 is essential for the development and progression of melanoma. MicroRNAs (miRNAs) can regulate the expression of transcription factors at the post-transcriptional level. The interactions between SOX10 and its targeting miRNAs form network motifs such as feedforward and feedback loops. Such motifs can result in nonlinear dynamics in gene expression levels, therefore playing a crucial role in regulating tumor proliferation and metastasis as well as the tumor's responses to therapies. Here, we reviewed and discussed the intricate interplay between SOX10 and miRNAs in melanoma biology including melanogenesis, phenotype switch, and therapy resistance. Additionally, we investigated the gene regulatory interactions in melanoma, identifying crucial network motifs that involve SOX10, MITF, and miRNAs. We also analyzed the expression levels of the components within these motifs. From a control theory perspective, we explained how these dynamics are linked to the phenotypic plasticity of melanoma cells. In summary, we underscored the importance of employing a data-driven network biology approach to elucidate the complex regulatory mechanisms and identify driver network motifs within the melanoma network. This methodology facilitates a deeper understanding of the regulation of SOX10 and MITF by miRNAs in melanoma. The insight gained could potentially contribute to the development of miRNA-based treatments, thereby enhancing the clinical management of this malignancy.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cachexia-induced reprogramming of visceral organ metabolism by human pancreatic cancer xenografts","authors":"Raj Kumar Sharma,&nbsp;Paul T. Winnard Jr.,&nbsp;Santosh Kumar Bharti,&nbsp;Balaji Krishnamachary,&nbsp;Yelena Mironchik,&nbsp;Marie-France Penet,&nbsp;Zaver M. Bhujwalla","doi":"10.1002/ijc.35487","DOIUrl":"10.1002/ijc.35487","url":null,"abstract":"<p>Pancreatic cancer patients with cachexia experience functional changes in visceral organs. To further understand these functional changes, here, for the first time, we characterized metabolic changes in the spleen, liver, pancreas, lungs, heart, and kidneys induced by human pancreatic cancer xenografts. These studies identify the commonality and consequences of cachexia-induced visceral organ metabolic dysregulation. The heart, kidneys, liver, lungs, pancreas, and spleen from euthanized non-tumor-bearing control mice and from cachexia-inducing Pa04C and non-cachexia-inducing Panc1 tumor-bearing mice (<i>n</i> = 8–10 per group) were metabolically characterized with 1H magnetic resonance spectroscopy. All visceral organs, with the exception of lungs, exhibited significant weight reduction in cachectic Pa04C mice relative to normal and non-cachectic Panc1 mice. A significant reduction (<i>p</i> ≤ .0166) of organ metabolites ranging from the amino acids leucine, isoleucine, valine, alanine, lysine, arginine, asparagine, glutamate, glutamine, aspartate, glycine, tyrosine, and phenylalanine, along with glucose, lactate, creatine, choline, and fumarate, depending upon the visceral organ, was observed in cachectic Pa04C mice compared to normal mice. The highest number of metabolites was reduced in the spleen, followed by the kidneys, lungs, and liver. The metabolic changes identified can lead to negative consequences in organ function by impacting pathways involved in tissue regeneration and resolving inflammation at the cellular level in cachectic mice. These results highlight the visceral organ metabolic reprogramming that can occur with cancer-induced cachexia, an understanding of which can identify noninvasive biomarkers and metabolic interventions to reduce morbidity and mortality from pancreatic cancer.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"157 6","pages":"1232-1245"},"PeriodicalIF":5.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Randomised trial on treatment of vaginal high-grade squamous intraepithelial lesion: Self-administered vaginal imiquimod and laser vaporisation.","authors":"Mari Kiviharju, Annika Riska, Ilkka Kalliala, Maija Jakobsson, Annu Heinonen, Joakim Dillner, Pekka Nieminen, Karoliina Aro","doi":"10.1002/ijc.35497","DOIUrl":"https://doi.org/10.1002/ijc.35497","url":null,"abstract":"<p><p>High grade vaginal squamous intraepithelial lesion (HSIL) (or vaginal intraepithelial neoplasia; VAIN) is a rare human papillomavirus (HPV)-related cancer precursor, which is commonly treated with laser vaporisation or other surgical methods to prevent progression to invasion. Vaginal HSIL has a substantial tendency to relapse despite treatment, for which HPV persistence is a known risk factor. Imiquimod is a topically applied immunomodulator and has shown promise in the treatment of high-grade HPV-related genital cancer precursors. The aim of this study was to assess the efficacy and patient compliance of self-administered vaginal imiquimod in comparison to laser vaporisation in the treatment of vaginal HSIL. We recruited 56 women with histological vaginal HSIL into a randomised controlled trial of laser vaporisation and self-administered vaginal imiquimod with follow-up up to 6 months. Follow-up visits included colposcopy, punch biopsies, and cervical or vaginal swabs for HPV genotyping. In per protocol analyses of 26 women in the laser arm and 27 women in the imiquimod arm, 53.8% and 77.8% (p = 0.07), respectively, showed histological regression at the end of the study. No progressions to invasion were detected during the study period. Genotype-specific post-treatment negativity for HPV occurred in 16.7% of the laser group and in 39.1% of the imiquimod group (p = 0.12). Imiquimod had short-term adverse effects, but 93% completed treatment as instructed. We conclude that vaginal imiquimod is an effective treatment for vaginal HSIL and could be considered an alternative to laser vaporisation.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mass cytometric detection of homologous recombination proficiency in circulating tumor cells to predict chemoresistance of metastatic breast cancer patients.","authors":"Kathrin Niedermayer, Henning Schäffler, Georgios Vlachos, Sara Greco, Kerstin Pfister, Barbara Volz, Leonie Ott, Hans Neubauer, Bernhard Polzer, André Koch, Sabine Riethdorf, Tanja Fehm, Wolfgang Janni, Thomas W P Friedl, Brigitte Rack, Ellen Heitzer, Fabienne Schochter, Lisa Wiesmüller","doi":"10.1002/ijc.35498","DOIUrl":"https://doi.org/10.1002/ijc.35498","url":null,"abstract":"<p><p>Circulating tumor cells (CTCs) can serve as a liquid biopsy to gain insight into treatment responses and metastatic recurrence. Due to their rarity, the analysis of CTCs is challenging and commonly based on immunomagnetic technologies using antibodies against EpCAM. This study used mass cytometry (CyTOF®) for the identification and characterization of CTCs from longitudinally monitored metastatic breast cancer (mBC) patients. Functional analysis focused on DNA damage responses, particularly the DNA repair pathway of homologous recombination (HR) validated in BC cells from the pleura. Fifty-two blood samples from 13 mBC patients were collected for the enumeration of CTCs using CellSearch® technology, isolation of CTCs together with peripheral blood mononuclear cells (PBMCs) and of plasma. Cell-free DNA (cfDNA) from plasma was analyzed by shallow genome sequencing to determine tumor fraction (TF) and HR deficiency (HRD). CTC/PBMC mixtures were phenotyped by CyTOF® using a panel of 13 antibodies including anti-γH2AX, 53BP1, and RAD51. CyTOF® identified CTCs correlating with CellSearch®- and cfDNA-based quantifications, detected DNA damage in CTCs, and the dynamics of their HR status during genotoxic therapies. Our study shows that CyTOF®-based phenotyping of CTCs from mBC patients shows promise as a method to monitor tumor progression and HR proficiency in real time for the identification of chemoresistance.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient factors and modifications to intended chemotherapy for women with Stages I-IIIA breast cancer.","authors":"Jenna Bhimani, Peng Wang, Grace B Gallagher, Kelli O'Connell, Victoria Blinder, Rachael Burganowski, Isaac J Ergas, Jennifer J Griggs, Narre Heon, Tatjana Kolevska, Yuriy Kotsurovskyy, Candyce H Kroenke, Cecile A Laurent, Raymond Liu, Kanichi G Nakata, Sonia Persaud, Janise M Roh, Sara Tabatabai, Emily Valice, Elisa V Bandera, Erin J Aiello Bowles, Lawrence H Kushi, Elizabeth D Kantor","doi":"10.1002/ijc.35494","DOIUrl":"10.1002/ijc.35494","url":null,"abstract":"<p><p>Modifications to intended chemotherapy regimens may be due to various reasons and may impact patient outcomes. Understanding which factors are associated with chemotherapy modifications can help inform treatment planning and improve cancer care. We examined the association between patient/tumor factors and modifications to intended chemotherapy in women with Stages I-IIIA breast cancer who were treated at Kaiser Permanente Northern California and Kaiser Permanente Washington from 2005 to 2019. Modifications were defined as any dose reductions in the first cycle or throughout chemotherapy, regimen change, treatment delay (single delay >14 days) or receiving fewer cycles of any drugs than expected. We used generalized linear models of the Poisson family with a log-link function to calculate prevalence ratios (PRatios). Of 9700 women receiving adjuvant chemotherapy, 34.6% had chemotherapy modifications. Selected results are shown: positive associations were observed with age (PRatio_{80+ vs. 18-39}: 1.93; 95% confidence interval [CI]: 1.50-2.50; p-trend <.001), body mass index (BMI) (PRatio_{≥35 vs. 18.5 to <25}: 1.53; 95% CI: 1.41-1.65; p-trend <.001), and Charlson comorbidity index (PRatio_{3+ vs. 0}: 1.33; 95% CI: 1.19-1.48; p-trend <.001), while more recent years of diagnosis were associated with decreased prevalence of treatment modifications (PRatio_{2015-2019 vs. 2005-2009}: 0.65; 95% CI: 0.61-0.69; p-trend <.001). Stage was also positively associated (PRatio_{Stage IIIA vs. I}: 1.24; 95% CI: 1.13-1.35; p-trend <.001), as was human epidermal growth factor-2 positive status (PRatio: 1.99; 95% CI: 1.89-2.10). In conclusion, patients with the highest likelihood of chemotherapy modifications represent those who may have more complex prescribing needs, including those of older age, higher BMI, and more comorbidity. Further understanding of how modifications could impact outcomes within these groups can inform and improve cancer care.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Socioeconomic impact among and socioeconomic support services for adolescents and young adults with cancer: A European perspective.","authors":"Julie M Vancoppenolle, Silvie H M Janssen, Nora Franzen, Winette T A van der Graaf, Valesca Retel, Olga Husson, Wim van Harten","doi":"10.1002/ijc.35488","DOIUrl":"https://doi.org/10.1002/ijc.35488","url":null,"abstract":"<p><p>Adolescent and young adult (AYA) cancer patients (15-39 years at initial cancer diagnosis) have distinct needs setting them apart from other age groups. Research shows that the socioeconomic impact (SEI) of cancer is more severe for AYAs than for older adults, and that employment and financial outcomes of AYAs are significantly different from matched peers without cancer, both on the short- and long-term. This study examines the SEI of cancer on AYAs and the availability and characteristics of socioeconomic support systems in 11 European countries. Two survey studies explored the SEI of cancer among AYAs and the support systems available in Europe. The SEC study (N = 3157) is a cross-sectional European study exploring the SEI of cancer from the patient's perspective. In this study, a sub-analysis has been conducted on the AYAs. Additionally, a survey targeting healthcare providers (HCPs) was conducted to contextualize the SEC-AYA data and identify local and national support systems. The first survey study included 577 AYAs, of which 75% reported financial difficulties and 65% experienced income loss. Seventy percent of AYAs made efforts to increase financial resources, such as using savings or borrowing money, to cover treatment-related expenses. Forty percent of AYAs faced challenges in obtaining financial services, like mortgages. Among 41 participating HCPs, 54% routinely discussed financial difficulties, yet 68% were unaware of AYAs' financial challenges. Available services for treatment-related income loss, work reintegration, and financial services are often not AYA-specific. European AYAs with cancer face significant SEI challenges, highlighting the need for targeted socioeconomic support and national guidelines tailored to AYAs. Future research should focus on establishing AYA-specific services and policies to improve outcomes for AYAs with cancer.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional repression of SOX2 by p53 in cancer cells regulates cell identity and migration","authors":"Patricia Lado-Fernández,&nbsp;Jéssica M. Vilas,&nbsp;Tânia Fernandes,&nbsp;Carmen Carneiro,&nbsp;Sabela Da Silva-Álvarez,&nbsp;Valentín Estévez-Souto,&nbsp;Pablo Pedrosa,&nbsp;Miguel González-Barcia,&nbsp;Luis E. Abatti,&nbsp;Jennifer A. Mitchell,&nbsp;Carmen Rivas,&nbsp;Gema Moreno-Bueno,&nbsp;Anxo Vidal,&nbsp;Manuel Collado","doi":"10.1002/ijc.35490","DOIUrl":"10.1002/ijc.35490","url":null,"abstract":"<p>During cancer development and progression, many genetic alterations lead to the acquisition of novel features that confer selective advantage to cancer cells and that resemble developmental programs. SRY-box transcription factor 2 (SOX2) is one of the key pluripotency transcription factors, expressed during embryonic development and active in adult stem cells. In cancer, <i>SOX2</i> is frequently dysregulated and associated with tumor stemness and poor patient survival. <i>SOX2</i> expression is suppressed in differentiated cells by tumor suppressor proteins that form a transcriptional repressive complex. We previously identified some of these proteins and found that their absence combined with deficiency in Trp53 leads to maximal dysregulated expression of <i>Sox2</i>. Using cancer cell lines of different origin and with different p53 status, we show here that manipulating <i>TP53</i> to restore or decrease its activity results in repression or induction of <i>SOX2</i>, respectively. Mechanistically, we observed that the regulation of <i>SOX2</i> expression by <i>TP53</i> is transcriptional and identified Trp53 bound to the promoter region and the <i>Sox2 Regulatory Region 2</i> enhancer of <i>Sox2</i>. Forcing high levels of <i>SOX2</i> in cancer cells leads to morphological changes that molecularly correspond to the acquisition of a more mesenchymal phenotype, correlating with an increased migratory capacity. Finally, the analysis of human breast cancer samples shows that this correlation between TP53 status, levels of expression of <i>SOX2</i>, and a more metastatic phenotype is also observed in cancer patients. Our results support the notion that lack of TP53 in tumor cells results in deregulated expression of developmental gene <i>SOX2</i> with phenotypic consequences related to increased malignization.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"157 5","pages":"980-992"},"PeriodicalIF":5.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.35490","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207284","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":"Germline pathogenic variants in HIC1 DNA binding domains are associated with familial serrated polyposis syndrome","authors":"Xavier Domínguez-Rovira,&nbsp;Coral Arnau-Collell,&nbsp;Gemma Gonfaus-Ortiz,&nbsp;Gemma Llargués-Sistac,&nbsp;Jenifer Muñoz,&nbsp;Ainara Llopis,&nbsp;Yasmin Soares de Lima,&nbsp;Cristina Herrera-Pariente,&nbsp;Leticia Moreira,&nbsp;Teresa Ocaña,&nbsp;Marcos Díaz-Gay,&nbsp;Miriam Cuatrecasas,&nbsp;Sabela Carballal,&nbsp;Anael López-Novo,&nbsp;Guerau Fernàndez,&nbsp;Antoni Castells,&nbsp;Luis Bujanda,&nbsp;Gabriel Capellà,&nbsp;Joaquín Cubiella,&nbsp;Daniel Rodríguez-Alcalde,&nbsp;Laura Valle,&nbsp;Francesc Balaguer,&nbsp;Clara Ruiz-Ponte,&nbsp;Laia Bonjoch,&nbsp;Sergi Castellví-Bel","doi":"10.1002/ijc.35492","DOIUrl":"10.1002/ijc.35492","url":null,"abstract":"<p>Serrated polyposis syndrome (SPS) is characterized by multiple and/or large serrated polyps and increased colorectal cancer (CRC) risk. Germline predisposition to SPS is mostly undetermined. We aimed to identify a new inherited SPS predisposition component by functionally evaluating a candidate gene replicated in two independent SPS cohorts. Exome sequencing was performed in a discovery cohort of 39 patients from 16 SPS families, and validation of relevant results was performed by multi-gene panel sequencing in 211 independent SPS patients. Considering the discovery and validation cohorts, three predicted pathogenic missense variants were identified in <i>HIC1</i> (Hypermethylated in cancer 1): c.110C&gt;T (p.Ala37Val), c.1295A&gt;G (p.Gln432Arg), and c.1411G&gt;A (p.Gly471Arg). <i>HIC1</i> is a tumor suppressor gene which encodes a transcriptional repressor involved in the DNA damage response, and it is commonly silenced in several cancers and serrated polyps. Two cellular models for <i>HIC1</i>, a CRISPR/Cas9 knockout model and an overexpression model, were produced. In these in vitro models, we assessed DNA damage levels and the SIRT1 regulatory pathway in the presence and absence of the identified variants. Compared to HIC1 wild-type, models harboring the HIC1 variants identified in SPS patients showed higher p-H2AX levels (marker of DNA damage) and impaired HIC1 binding to the <i>SIRT1</i> promoter. Our results indicate that <i>HIC1</i> genetic variants located in the zinc finger region affected its transcriptional repressor role. We can conclude that <i>HIC1</i> may be involved in germline predisposition to SPS through an alteration of its repressor capacity and a faulty DNA damage response, as a molecular mechanism.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"157 6","pages":"1154-1167"},"PeriodicalIF":5.7,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.35492","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186112","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":"Prognostic impact of p16 and high-risk HPV DNA in ~1300 patients with vulvar cancer.","authors":"Susanne K Kjær, Kirsten Frederiksen, Christina L Rasmussen, Louise T Thomsen, Else M Madsen, Maria B Franzmann, Alexander K Kjær, Lise G Larsen, Nadia V Salinas, Doris Schledermann, Birgitte H Winberg, Pernille T Jensen, Dorthe Ørnskov, Marianne Waldstrøm, Louise Baandrup","doi":"10.1002/ijc.35501","DOIUrl":"https://doi.org/10.1002/ijc.35501","url":null,"abstract":"<p><p>The study aimed to investigate whether vulvar squamous cell carcinoma (VSCC) survival varies by human papillomavirus (HPV) status measured by p16 expression and to determine whether high-risk HPV (hrHPV) DNA detection adds further prognostic information. Our cohort included 1277 women with histologically verified VSCC (1990-2017) categorized according to p16 and hrHPV DNA. Crude survival was estimated using Kaplan-Meier, and differences in restricted mean survival time were estimated in linear regression models. Analyses were stratified by p16 and p16/hrHPV status and stage, and adjustment included age, calendar year, and comorbidity. Overall analysis showed that 5-year survival was 67% (95% CI: 63-71%) and 45% (95% CI: 42-48%) in p16-positive and p16-negative VSCC, respectively. Overall, detection of hrHPV was associated with a 23% (95% CI: 6-40%) improvement in 5-year survival in p16-positive VSCC, whereas hrHPV status did not impact 5-year survival in p16-negative VSCC. In adjusted analysis, the survival difference by p16 status increased with increasing stage with a 26% (95% CI: 4-46%) higher 5-year survival in FIGO IV disease if the tumor was p16-positive compared to p16-negative, corresponding to a restricted mean survival time difference of 18 months in favor of p16 positivity. The largest VSCC cohort to date confirms the beneficial prognostic impact of p16 expression regardless of age and comorbidity and with the greatest impact in women with advanced disease. Classification according to p16 was adequate for p16-negative VSCC, whereas the survival of p16-positive VSCC was higher if hrHPV testing was also positive.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}