TY - JOUR AU - Barreca, Marco AU - Dugo, Matteo AU - Galbardi, Barbara AU - Győrffy, Balázs AU - Valagussa, Pinuccia AU - Besozzi, Daniela AU - Viale, Giuseppe AU - Bianchini, Giampaolo AU - Gianni, Luca AU - Callari, Maurizio ED - Gianni, Luca / Collaborator ED - Bisagni, Giancarlo / Collaborator ED - Colleoni, Marco / Collaborator ED - Del Mastro, Lucia / Collaborator ED - Zamagni, Claudio / Collaborator ED - Mansutti, Mauro / Collaborator ED - Zambetti, Milvia / Collaborator ED - Frassoldati, Antonio / Collaborator ED - Gianni, Luca / Collaborator ED - Montemurro, Filippo / Collaborator ED - Zamagni, Claudio / Collaborator ED - Del Mastro, Lucia / Collaborator ED - Bengala, Carmelo / Collaborator ED - Colleoni, Marco / Collaborator ED - Mariani, Gabriella / Collaborator ED - Gambaro, Anna / Collaborator ED - Zambelli, Stefania / Collaborator ED - Bianchini, Giampaolo / Collaborator ED - Bisagni, Giancarlo / Collaborator ED - Russo, Stefania / Collaborator ED - Huang, Chiun-Sheng / Collaborator ED - Chen, Shou-Tung / Collaborator ED - Hou, Ming Feng / Collaborator ED - Liu, Liang-Chih / Collaborator ED - Tseng, Ling Ming / Collaborator ED - Kelly, Catherine / Collaborator ED - O'Reilly, Seamus / Collaborator ED - Morris, Patrick / Collaborator ED - Kennedy, John / Collaborator ED - O'Connor, Miriam / Collaborator ED - Greil, Richard / Collaborator ED - Egle, Daniel / Collaborator ED - Thill, Mark / Collaborator ED - Sagasser, Jacqueline / Collaborator ED - Graffunder, Gerd / Collaborator ED - Behringer, Dirk / Collaborator ED - Tesch, Hans / Collaborator ED - Lück, Hans-Joachim / Collaborator ED - Schneeweiss, Andreas / Collaborator ED - Schumacher, Claudia / Collaborator ED - Malter, Wolfram / Collaborator ED - Semiglazov, Vladimir / Collaborator ED - Frolova, Mona / Collaborator ED - Gennadievich, Alexander Vasiliev / Collaborator ED - Volkov, Nikita / Collaborator ED - Bermejo, Begoña / Collaborator ED - Falo, Catalina / Collaborator ED - Sevillano, Elena / Collaborator ED - Ciruelos Gil, Eva Maria / Collaborator ED - García Sáenz, José Ángel / Collaborator ED - Antón-Torres, Anton / Collaborator TI - Development and validation of a gene expression-based Breast Cancer Purity Score JF - NPJ PRECISION ONCOLOGY J2 - NPJ PRECIS ONCOL VL - 8 PY - 2024 IS - 1 PG - 11 SN - 2397-768X DO - 10.1038/s41698-024-00730-7 UR - https://m2.mtmt.hu/api/publication/35501912 ID - 35501912 AB - The prevalence of malignant cells in clinical specimens, or tumour purity, is affected by both intrinsic biological factors and extrinsic sampling bias. Molecular characterization of large clinical cohorts is typically performed on bulk samples; data analysis and interpretation can be biased by tumour purity variability. Transcription-based strategies to estimate tumour purity have been proposed, but no breast cancer specific method is available yet. We interrogated over 6000 expression profiles from 10 breast cancer datasets to develop and validate a 9-gene Breast Cancer Purity Score (BCPS). BCPS outperformed existing methods for estimating tumour content. Adjusting transcriptomic profiles using the BCPS reduces sampling bias and aids data interpretation. BCPS-estimated tumour purity improved prognostication in luminal breast cancer, correlated with pathologic complete response in on-treatment biopsies from triple-negative breast cancer patients undergoing neoadjuvant treatment and effectively stratified the risk of relapse in HER2+ residual disease post-neoadjuvant treatment. LA - English DB - MTMT ER - TY - JOUR AU - Ungvári, Zoltán István AU - Ungvári, Anna Sára AU - Fekete, Mónika AU - Kiss, Csaba AU - Győrffy, Balázs TI - Senescence-related genes as prognostic indicators in breast cancer survival. JF - GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE) J2 - GEROSCIENCE VL - in press PY - 2024 SP - in press SN - 2509-2715 DO - 10.1007/s11357-024-01384-w UR - https://m2.mtmt.hu/api/publication/35473003 ID - 35473003 AB - Breast cancer is a leading cause of cancer-related mortality among women worldwide, particularly affecting those in their later years. As the incidence of breast cancer increases with age, understanding the biological mechanisms that link aging and cancer becomes crucial. Cellular senescence, a hallmark of aging, plays a dual role in cancer by inhibiting tumorigenesis while also contributing to tumor progression through the senescence-associated secretory phenotype (SASP). This study aims to investigate the prognostic significance of senescence-related genes in breast cancer. We utilized the SenMayo gene list, a comprehensive set of senescence-related genes, to analyze gene expression data from a large cohort of breast cancer samples. The data was sourced from the Kaplan-Meier plotter, an integrated database that compiles gene expression information from multiple independent cohorts. Cox proportional hazards regression and false discovery rate (FDR) corrections were employed to evaluate the correlation between gene expression and survival outcomes, aiming to establish a prognostic signature. Our findings demonstrate that higher expression levels of senescence-related genes are significantly associated with improved survival, while lower expression levels correlate with shorter survival outcomes. These results suggest that senescence-related pathways play a protective role in breast cancer, potentially serving as valuable prognostic indicators. The identification of a prognostic signature based on senescence-related genes underscores the importance of cellular senescence in breast cancer progression and survival. Our study highlights the potential of senescence-related biomarkers in enhancing patient stratification and informing treatment strategies, contributing to the growing body of literature on the intersection of aging and cancer. LA - English DB - MTMT ER - TY - JOUR AU - Ungvári, Zoltán István AU - Fekete, Mónika AU - Varga, Péter AU - Lehoczki, Andrea Marianna AU - Fekete, János Tibor AU - Ungvári, Anna Sára AU - Győrffy, Balázs TI - Overweight and obesity significantly increase colorectal cancer risk: a meta-analysis of 66 studies revealing a 25–57% elevation in risk JF - GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE) J2 - GEROSCIENCE VL - In press PY - 2024 SP - In press SN - 2509-2715 DO - 10.1007/s11357-024-01375-x UR - https://m2.mtmt.hu/api/publication/35447386 ID - 35447386 AB - The incidence of colorectal cancer (CRC) has been steadily rising, and obesity has been identified as a significant risk factor. Numerous studies suggest a strong correlation between excess body weight and increased risk of CRC, but comprehensive quantification through pooled analysis remains limited. This study aims to systematically review and meta-analyze the existing literature to evaluate the association between obesity and CRC risk, considering variations across sex and study designs. A systematic literature search was conducted in PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science to identify randomized controlled trials and human clinical trials from 1992 to 2024. Statistical analysis was performed using the https://metaanalysisonline.com web application using a random effects model to estimate the pooled hazard rates (HR). Forest plots, funnel plots, and Z-score plots were utilized to visualize results. We identified 52 clinical trials and 14 case–control studies, encompassing a total of 83,251,050 and 236,877 subjects, respectively. The pooled analysis indicated that obesity significantly increased the prevalence of CRC (HR = 1.36, 95% CI = 1.24–1.48, p < 0.01). This effect was consistent across sexes, with HRs of 1.57 (95% CI = 1.38–1.78, p = 0.01) for males and 1.25 (95% CI = 1.14–1.38, p < 0.01) for females. Case–control studies specifically showed an effect, but with marginal significance only (HR = 1.27, 95% CI = 0.98–1.65, p = 0.07). The Z-score plot indicated the need for additional analysis in the case–control group. A significant heterogeneity was observed across studies in all four settings. This meta-analysis provides robust evidence that obesity is a significant risk factor for colorectal cancer, with an overall hazard rate indicating a 36% increased risk. The effect is pronounced across both sexes, with males showing a slightly higher risk compared to females. Although case–control studies showed a weaker association, the overall trend supports the link between obesity and CRC. These results underscore the importance of public health interventions aimed at reducing obesity to potentially lower the risk of colorectal cancer. LA - English DB - MTMT ER - TY - JOUR AU - Dugo, Matteo AU - Huang, Chiun-Sheng AU - Egle, Daniel AU - Bermejo, Begoña AU - Zamagni, Claudio AU - Seitz, Robert S AU - Nielsen, Tyler J AU - Thill, Marc AU - Antón-Torres, Antonio AU - Russo, Stefania AU - Ciruelos, Eva Maria AU - Schweitzer, Brock L AU - Ross, Douglas T AU - Galbardi, Barbara AU - Greil, Richard AU - Semiglazov, Vladimir AU - Győrffy, Balázs AU - Colleoni, Marco AU - Kelly, Catherine M AU - Mariani, Gabriella AU - Del Mastro, Lucia AU - Blasi, Olivia AU - Callari, Maurizio AU - Pusztai, Lajos AU - Valagussa, Pinuccia AU - Viale, Giuseppe AU - Gianni, Luca AU - Bianchini, Giampaolo TI - The Immune-Related 27-Gene Signature DetermaIO Predicts Response to Neoadjuvant Atezolizumab plus Chemotherapy in Triple-Negative Breast Cancer. JF - CLINICAL CANCER RESEARCH J2 - CLIN CANCER RES PY - 2024 SN - 1078-0432 DO - 10.1158/1078-0432.CCR-24-0149 UR - https://m2.mtmt.hu/api/publication/35427260 ID - 35427260 AB - We assessed the 27-gene RT-qPCR-based DetermaIO assay and the same score calculated from RNA sequencing (RNA-seq) data as predictors of sensitivity to immune checkpoint therapy in the neoTRIPaPDL1 randomized trial that compared neoadjuvant carboplatin/nab-paclitaxel chemotherapy (CT) plus atezolizumab with CT alone in stage II/III triple-negative breast cancer. We also assessed the predictive function of the immuno-oncology (IO) score in expression data of patients treated with pembrolizumab plus paclitaxel (N = 29) or CT alone (N = 56) in the I-SPY2 trial.RNA-seq data were obtained from pretreatment core biopsies from 242 (93.8%) of the 258 patients in the per-protocol-population. The DetermaIO RT-qPCR test, performed in the CAP/CLIA-accredited laboratory of Oncocyte Corp., was available for 220 patients (85.3%). A previously established threshold was used to assign DetermaIO-positive versus DetermaIO-negative status. Publicly available microarray data were used from I-SPY2.IO scores calculated from RNA-seq and RT-qPCR data were highly concordant. In neoTRIPaPDL1, DetermaIO-positive cancers (N = 92, 41.8%) had pathologic complete response (pCR) rates of 69.8% and 46.9% in the CT + atezolizumab and CT arms, respectively. In DetermaIO-negative cases, pCR rates were similar in both arms (44.6% vs. 49.2%; interaction test P = 0.04). PDL1 protein expression and stromal tumor-infiltrating lymphocyte count were not predictive of differential benefit from atezolizumab. In I-SPY2, IO-positive cancers (45.9%) had pCR rates of 85.7% and 16%, with and without immunotherapy, respectively. In IO-negative cancers, pCR rates were 46.7% versus 16.1%.DetermaIO identified patients who benefited from neoadjuvant immunotherapy resulting in improved pCR rate, independently of PDL1. LA - English DB - MTMT ER - TY - JOUR AU - Menyhart, Otilia AU - Fekete, János Tibor AU - Győrffy, Balázs TI - Inflammation and Colorectal Cancer: A Meta-Analysis of the Prognostic Significance of the Systemic Immune-Inflammation Index (SII) and the Systemic Inflammation Response Index (SIRI) JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 15 PG - 18 SN - 1661-6596 DO - 10.3390/ijms25158441 UR - https://m2.mtmt.hu/api/publication/35172447 ID - 35172447 AB - The overall prognosis for colorectal cancer (CRC) remains challenging as the survival time varies widely, even in patients with the same stage of disease. Recent studies suggest prognostic relevance of the novel markers of systemic inflammation, the systemic immune-inflammation index (SII), and the systemic inflammation response index (SIRI). We conducted a comprehensive meta-analysis to assess the prognostic significance of the SII and the SIRI in CRC. We searched the relevant literature for observational studies, and random effects models were employed to conduct a statistical analysis using the metaanalysisonline.com platform. Pooled effect sizes were reported with hazard ratios (HRs) and corresponding 95% confidence intervals (CI). Data from 29 studies published between 2016 and 2024, comprising 10,091 participants, were included in our meta-analysis on SII. CRC patients with high SII levels had worse disease outcomes, which were associated with poor OS (HR: 1.75; 95% CI: 1.4-2.19) and poor PFS/DFS/RFS (HR: 1.25; 95% CI: 1.18-1.33). This increased risk of worse OS was present irrespective of the treatment strategy, sample size (<220 and >= 220), and cutoff used to define high and low SII (<550 and >= 550) groups. Based on data from five studies comprising 2362 participants, we found a strong association between the high SIRI and worse OS (HR: 2.65; 95% CI: 1.6-4.38) and DFS/RFS (HR: 2.04; 95% CI: 1.42-2.93). According to our results, both the SII and SIRI hold great promise as prognostic markers in CRC. Further validations are needed for their age- and stage-specific utility in the clinical routine. LA - English DB - MTMT ER - TY - JOUR AU - Ungvári, Zoltán István AU - Fekete, Mónika AU - Fekete, János Tibor AU - Grosso, Giuseppe AU - Ungvári, Anna Sára AU - Győrffy, Balázs TI - Adherence to the Mediterranean diet and its protective effects against colorectal cancer: a meta-analysis of 26 studies with 2,217,404 participants JF - GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE) J2 - GEROSCIENCE VL - In press PY - 2024 PG - 17 SN - 2509-2715 DO - 10.1007/s11357-024-01296-9 UR - https://m2.mtmt.hu/api/publication/35162223 ID - 35162223 N1 - Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, United States Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States International Training Program in Geroscience, Doctoral College/Institute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary Institute of Preventive Medicine and Public Health, Semmelweis University, Semmelweis University, Budapest, Hungary Department of Bioinformatics, Semmelweis University, Budapest, 1094, Hungary Cancer Biomarker Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Budapest, H-1117, Hungary Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy Center for Human Nutrition and Mediterranean Foods (NUTREA), University of Catania, Catania, Italy Department of Biophysics, Medical School, University of Pecs, Pecs, H-7624, Hungary Cited By :1 Export Date: 23 September 2024 Correspondence Address: Ungvari, A.; Institute of Preventive Medicine and Public Health, Hungary; email: Ungann2004@gmail.com Funding details: Ministry of Innovation, Science and Technology, MOST Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA Funding details: RRF-2.3.1–21-2022–00015, 135784 Funding details: 101004093/ EUniWell/EAC-A02-2019 / EAC-A02-2019–1 Funding details: National Cancer Institute, NCI, R01CA255840, TKP2021-NKTA-47 Funding details: National Cancer Institute, NCI Funding details: National Institute on Aging, NIA, R01AG068295, R01AG070915, RF1AG072295, R01AG055395 Funding details: National Institute on Aging, NIA Funding details: National Institute of Neurological Disorders and Stroke, NINDS, R01NS100782 Funding details: National Institute of Neurological Disorders and Stroke, NINDS Funding details: RRF-2.3.1–21-2022–00003 Funding text 1: Open access funding provided by Semmelweis University. This work was supported by grants from the National Institute on Aging (RF1AG072295, R01AG055395, R01AG068295; R01AG070915), the National Institute of Neurological Disorders and Stroke (R01NS100782), the National Cancer Institute (R01CA255840). AU was supported by TKP2021-NKTA-47, implemented with the support provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-NKTA funding scheme, by funding through the National Cardiovascular Laboratory Program (RRF-2.3.1\\u201321-2022\\u201300003) and by the National Laboratory for Drug Research and Development (PharmaLab, RRF-2.3.1\\u201321-2022\\u201300015) provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, Project no. 135784 implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the K20 funding scheme and the European University for Well-Being (EUniWell) program (grant agreement number: 101004093/ EUniWell/EAC-A02-2019 / EAC-A02-2019\\u20131). The 4.0 version of ChatGPT, developed by OpenAI, was used as a language tool to refine our writing, enhancing the clarity of our work. AB - Colorectal cancer (CRC) is a major global health concern and represents a significant public health challenge in Hungary, where it exhibits some of the highest morbidity and mortality rates in the European Union. The Mediterranean diet has been suggested to reduce the incidence of CRC, but comprehensive evidence from diverse study designs is needed to substantiate this effect. A systematic literature search was conducted in PubMed, ClinicalTrials.gov, CENTRAL, and the Web of Science to identify randomized controlled trials and human clinical trials from 2008 to 2024 to identify relevant studies. Statistical analysis was performed using the https://metaanalysisonline.com web application using a random effects model to estimate the pooled hazard rates (HRs). Forest plots, funnel plots, and Z -score plots were utilized to visualize results. We identified 15 clinical trials and 9 case–control studies, encompassing a total of 2,217,404 subjects. The pooled analysis indicated that adherence to the Mediterranean diet significantly reduced the prevalence of CRC (HR = 0.84, 95% CI = 0.78–0.91, p < 0.01). This protective effect was consistent across sexes, with HRs of 0.85 (95% CI = 0.75–0.97, p = 0.01) for males and 0.88 (95% CI = 0.79–0.99, p = 0.03) for females. Case–control studies specifically showed a substantial effect (HR = 0.51, 95% CI = 0.38–0.68, p < 0.01). Notable heterogeneity was observed across studies, yet the a priori information size was substantially below the cumulative sample size, ensuring sufficient data for reliable conclusions. The findings from this meta-analysis reinforce the protective role of the Mediterranean diet against CRC. The results of this meta-analysis will inform dietary interventions designed to mitigate CRC risk, which are conducted within the framework of the Semmelweis Study, an ongoing comprehensive cohort study at Semmelweis University, designed to explore the multifaceted causes of unhealthy aging in Hungary. These interventions aim to explore the practical application of Mediterranean dietary patterns in reducing CRC incidence among the Hungarian population. LA - English DB - MTMT ER - TY - JOUR AU - Witalisz-Siepracka, A. AU - Denk, C.-M. AU - Zdársky, B. AU - Hofmann, L. AU - Edtmayer, S. AU - Harm, T. AU - Weiss, S. AU - Heindl, K. AU - Hessenberger, M. AU - Summer, S. AU - Dutta, S. AU - Casanova, E. AU - Obermair, G.J. AU - Győrffy, Balázs AU - Putz, E.M. AU - Sill, H. AU - Stoiber, D. TI - STAT3 in acute myeloid leukemia facilitates natural killer cell-mediated surveillance JF - FRONTIERS IN IMMUNOLOGY J2 - FRONT IMMUNOL VL - 15 PY - 2024 PG - 15 SN - 1664-3224 DO - 10.3389/fimmu.2024.1374068 UR - https://m2.mtmt.hu/api/publication/35151889 ID - 35151889 N1 - Division Pharmacology, Department of Pharmacology, Physiology and Microbiology, Karl Landsteiner University of Health Sciences, Krems, Austria Division Physiology, Department of Pharmacology, Physiology and Microbiology, Karl Landsteiner University of Health Sciences, Krems, Austria Department for Biomedical Research, University for Continuing Education Krems, Krems, Austria Division of Oncology, Medical University of Graz, Graz, Austria Institute of Pharmacology, Center of Physiology and Pharmacology & Comprehensive Cancer Center (CCC), Medical University of Vienna, Vienna, Austria Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria Department of Bioinformatics, Semmelweis University, Budapest, Hungary Department of Biophysics, Medical School, University of Pecs, Pecs, Hungary Cancer Biomarker Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary St. Anna Children’s Cancer Research Institute (CCRI), Vienna, Austria Institute of Pharmacology, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria Division of Hematology, Medical University of Graz, Graz, Austria Export Date: 15 August 2024 Correspondence Address: Stoiber, D.; Division Pharmacology, Austria; email: dagmar.stoiber@kl.ac.at LA - English DB - MTMT ER - TY - JOUR AU - Park, S.H. AU - Ju, J.-S. AU - Woo, H. AU - Yun, H.J. AU - Lee, S.B. AU - Kim, S.-H. AU - Győrffy, Balázs AU - Kim, E.-J. AU - Kim, H. AU - Han, H.D. AU - Eyun, S.-I. AU - Lee, J.-H. AU - Park, Y.-Y. TI - The m6A writer RBM15 drives the growth of triple-negative breast cancer cells through the stimulation of serine and glycine metabolism JF - EXPERIMENTAL AND MOLECULAR MEDICINE J2 - EXP MOL MED VL - 56 PY - 2024 IS - 6 SP - 1373 EP - 1387 PG - 15 SN - 1226-3613 DO - 10.1038/s12276-024-01235-w UR - https://m2.mtmt.hu/api/publication/34972042 ID - 34972042 N1 - Department of Health Sciences, The Graduate School of Dong-A University, Busan, South Korea Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea Department of Life Science, Chung-Ang University, Seoul, South Korea Department of Medicinal Biotechnology, College of Health Science, Dong-A University, Busan, South Korea Department of Bioinformatics, Semmelweis University, Budapest, H-1094, Hungary Department of Biophysics, Medical School, University of Pecs, Pecs, H-7624, Hungary Cancer Biomarker Research Group, Institute of Molecular Life Sciences, Research Centre for Natural Sciences, Budapest, H-1117, Hungary Division of Life Science and Chemistry, College of Natural Science, Daejin University, Pocheon, South Korea Department of Immunology, School of Medicine, Konkuk University, Chungcheongbuk-Do, South Korea Export Date: 15 September 2024 CODEN: EMMEF Correspondence Address: Lee, J.-H.; Department of Health Sciences, South Korea; email: Topljh19@dau.ac.kr Correspondence Address: Eyun, S.-I.; Department of Life Science, South Korea; email: eyun@cau.ac.kr Correspondence Address: Park, Y.-Y.; Department of Life Science, South Korea; email: yunyong.park@gmail.com Chemicals/CAS: glycine, 56-40-6, 6000-43-7, 6000-44-8; serine, 56-45-1, 6898-95-9; adenosine, 58-61-7; Adenosine; Glycine; RNA-Binding Proteins; Serine Tradenames: AM1560, Ambion, United States; CCK-8, Dojindo, Japan; CytExpert software, Beckman Coulter, United States; CytoFLEX flow cytometer, Beckman Coulter, United States; easy-BLUE Total RNA Extraction Kit, INtRON; Illumina BeadArray Reade, Illumina, United States; K589, Biovision, United States; K743, Biovision, United States; mirVana RNA Isolation Kit, Ambion, United States; SensiFAST Probe Hi-ROX One-Step Kit, Bioline, United Kingdom Manufacturers: Bioline, United Kingdom; Dojindo, Japan; Ambion, United States; Beckman Coulter, United States; Biovision, United States; Illumina, United States; INtRON LA - English DB - MTMT ER - TY - JOUR AU - Edtmayer, Sophie AU - Witalisz-Siepracka, Agnieszka AU - Zdársky, Bernhard AU - Heindl, Kerstin AU - Weiss, Stefanie AU - Eder, Thomas AU - Dutta, Sayantanee AU - Graichen, Uwe AU - Klee, Sascha AU - Sharif, Omar AU - Wieser, Rotraud AU - Győrffy, Balázs AU - Poli, Valeria AU - Casanova, Emilio AU - Sill, Heinz AU - Grebien, Florian AU - Stoiber, Dagmar TI - A novel function of STAT3β in suppressing interferon response improves outcome in acute myeloid leukemia JF - CELL DEATH AND DISEASE J2 - CELL DEATH DIS VL - 15 PY - 2024 IS - 5 PG - 12 SN - 2041-4889 DO - 10.1038/s41419-024-06749-9 UR - https://m2.mtmt.hu/api/publication/34922169 ID - 34922169 N1 - Funding Agency and Grant Number: Austrian Science Fund (FWF); City of Vienna Fund for Innovative, Interdisciplinary Cancer Research; Italian Cancer Research Association [AIRC IG16930]; Gesellschaft fur Forschungsforderung Niederosterreich m.b.H. (GFF) [SC19-019, LSC19-019]; Landsteiner University of Health Sciences, Krems, Austria; National Research, Development, and Innovation Office (PharmaLab) [RRF-2.3.1-21-2022-00015] Funding text: The authors thank Johannes Zuber for the pMSCV-MLL-AF9-IRES-Venus construct. We thank Christoph Bock and the Biomedical Sequencing Facility of the Medical University of Vienna for help with RNA sequencing. We are grateful to Birgit Strobl, Karoline Kollmann, and Sebastian Kollmann for helpful discussions. We thank Petra Aigner and Tatsuaki Mizutani who provided expertise that assisted the research. Lastly, we would like to thank Jaqueline Horvath and all members of the animal facility for their support. This research was funded in whole or in part by the Austrian Science Fund (FWF, 10.55776/P32693 to DS, 10.55776/P36728, 10.55776/P33430, 10.55776/P32900 and 10.55776/DOC59 to EC), City of Vienna Fund for Innovative, Interdisciplinary Cancer Research to EC, Italian Cancer Research Association (AIRC IG16930) to VP, and Gesellschaft fur Forschungsforderung Niederosterreich m.b.H. (GFF, SC19-019 and LSC19-019) to DS. For open access purposes, the author has applied for a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission. We also acknowledge support by Open Access Publishing Fund of Karl Landsteiner University of Health Sciences, Krems, Austria. BG was supported by the National Research, Development, and Innovation Office (PharmaLab, RRF-2.3.1-21-2022-00015). SE is a PhD candidate at the Medical University of Vienna. This work is submitted in partial fulfillment of the requirement for a PhD. AB - Signal transducer and activator of transcription 3 (STAT3) is frequently overexpressed in patients with acute myeloid leukemia (AML). STAT3 exists in two distinct alternatively spliced isoforms, the full-length isoform STAT3α and the C-terminally truncated isoform STAT3β. While STAT3α is predominantly described as an oncogenic driver, STAT3β has been suggested to act as a tumor suppressor. To elucidate the role of STAT3β in AML, we established a mouse model of STAT3β-deficient, MLL-AF9-driven AML. STAT3β deficiency significantly shortened survival of leukemic mice confirming its role as a tumor suppressor. Furthermore, RNA sequencing revealed enhanced STAT1 expression and interferon (IFN) signaling upon loss of STAT3β. Accordingly, STAT3β-deficient leukemia cells displayed enhanced sensitivity to blockade of IFN signaling through both an IFNAR1 blocking antibody and the JAK1/2 inhibitor Ruxolitinib. Analysis of human AML patient samples confirmed that elevated expression of IFN-inducible genes correlated with poor overall survival and low STAT3β expression. Together, our data corroborate the tumor suppressive role of STAT3β in a mouse model in vivo. Moreover, they provide evidence that its tumor suppressive function is linked to repression of the STAT1-mediated IFN response. These findings suggest that the STAT3β/α mRNA ratio is a significant prognostic marker in AML and holds crucial information for targeted treatment approaches. Patients displaying a low STAT3β/α mRNA ratio and unfavorable prognosis could benefit from therapeutic interventions directed at STAT1/IFN signaling. LA - English DB - MTMT ER - TY - JOUR AU - Győrffy, Balázs TI - Integrated analysis of public datasets for the discovery and validation of survival-associated genes in solid tumors JF - INNOVATION(UNITED STATES) J2 - INNOVATION(UNITED STATES) VL - 5 PY - 2024 IS - 3 PG - 9 SN - 2666-6758 DO - 10.1016/j.xinn.2024.100625 UR - https://m2.mtmt.hu/api/publication/34831592 ID - 34831592 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office [RRF-2.3.1-21-2022-00015]; ELIXIR Hungary Funding text: This project was supported by the National Research, Development and Innovation Office (PharmaLab, RRF-2.3.1-21-2022-00015) . The author thanks Andras Lanczky for his help in updating the online platform. The support of ELIXIR Hungary ( www.bioinformatics.hu) is acaknowledged. LA - English DB - MTMT ER -