TY - JOUR AU - Ferencz, Bence AU - Török, Klára AU - Pipek, Orsolya Anna AU - Fillinger, János AU - Csende, Kristóf AU - Lantos, András AU - Černeková, Radoslava AU - Mitták, Marcel AU - Škarda, Jozef AU - Delongová, Patricie AU - Megyesfalvi, Evelyn AU - Schelch, Karin AU - Lang, Christian AU - Solta, Anna AU - Boettiger, Kristiina AU - Brcic, Luka AU - Lindenmann, Jörg AU - Rényi-Vámos, Ferenc István AU - Aigner, Clemens AU - Berta, Judit AU - Megyesfalvi, Zsolt AU - Döme, Balázs TI - Expression patterns of novel immunotherapy targets in intermediate- and high-grade lung neuroendocrine neoplasms JF - CANCER IMMUNOLOGY IMMUNOTHERAPY J2 - CANCER IMMUNOL IMMUN VL - 73 PY - 2024 IS - 6 SP - 114 SN - 1432-0851 DO - 10.1007/s00262-024-03704-7 UR - https://m2.mtmt.hu/api/publication/34839166 ID - 34839166 N1 - Journal Article; Multicenter Study AB - Advancements in immunotherapeutic approaches only had a modest impact on the therapy of lung neuroendocrine neoplasms (LNENs). Our multicenter study aimed to investigate the expression patterns of novel immunotherapy targets in intermediate- and high-grade LNENs.The expressions of V-domain Ig suppressor of T cell activation (VISTA), OX40L, Glucocorticoid-induced TNF receptor (GITR), and T cell immunoglobulin and mucin domain 3 (TIM3) proteins were measured by immunohistochemistry in surgically resected tumor samples of 26 atypical carcinoid (AC), 49 large cell neuroendocrine lung cancer (LCNEC), and 66 small cell lung cancer (SCLC) patients. Tumor and immune cells were separately scored.Tumor cell TIM3 expression was the highest in ACs (p < 0.001), whereas elevated tumor cell GITR levels were characteristic for both ACs and SCLCs (p < 0.001 and p = 0.011, respectively). OX40L expression of tumor cells was considerably lower in ACs (vs. SCLCs; p < 0.001). Tumor cell VISTA expression was consistently low in LNENs, with no significant differences across histological subtypes. ACs were the least immunogenic tumors concerning immune cell abundance (p < 0.001). Immune cell VISTA and GITR expressions were also significantly lower in these intermediate-grade malignancies than in SCLCs or in LCNECs. Immune cell TIM3 and GITR expressions were associated with borderline prognostic significance in our multivariate model (p = 0.057 and p = 0.071, respectively).LNEN subtypes have characteristic and widely divergent VISTA, OX40L, GITR, and TIM3 protein expressions. By shedding light on the different expression patterns of these immunotherapy targets, the current multicenter study provides support for the future implementation of novel immunotherapeutic approaches. LA - English DB - MTMT ER - TY - JOUR AU - Prosz, Aurel AU - Pipek, Orsolya Anna AU - Börcsök, Judit AU - Palla, Gergely AU - Szallasi, Zoltan AU - Spisák, Sándor AU - Csabai, István TI - Biologically informed deep learning for explainable epigenetic clocks JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 14 PY - 2024 IS - 1 PG - 10 SN - 2045-2322 DO - 10.1038/s41598-023-50495-5 UR - https://m2.mtmt.hu/api/publication/34527502 ID - 34527502 N1 - Danish Cancer Institute, Copenhagen, Denmark Department of Physics of Complex Systems, ELTE Eötvös Loránd University, Budapest, Hungary Biotech Research & Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark Department of Biological Physics, ELTE Eötvös Loránd University, Budapest, Hungary Health Services Management Training Centre, Semmelweis University, Budapest, Hungary Institute of Enzymology, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary Export Date: 13 February 2024; Cited By: 0; Correspondence Address: S. Spisak; Institute of Enzymology, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary; email: spisak.sandor@ttk.hu AB - Ageing is often characterised by progressive accumulation of damage, and it is one of the most important risk factors for chronic disease development. Epigenetic mechanisms including DNA methylation could functionally contribute to organismal aging, however the key functions and biological processes may govern ageing are still not understood. Although age predictors called epigenetic clocks can accurately estimate the biological age of an individual based on cellular DNA methylation, their models have limited ability to explain the prediction algorithm behind and underlying key biological processes controlling ageing. Here we present XAI-AGE, a biologically informed, explainable deep neural network model for accurate biological age prediction across multiple tissue types. We show that XAI-AGE outperforms the first-generation age predictors and achieves similar results to deep learning-based models, while opening up the possibility to infer biologically meaningful insights of the activity of pathways and other abstract biological processes directly from the model. LA - English DB - MTMT ER - TY - JOUR AU - Pipek, Orsolya Anna AU - Medgyes-Horváth, Anna AU - Stéger, József AU - Papp, Krisztián AU - Visontai, David AU - Koopmans, M. AU - Nieuwenhuijse, D. AU - Oude, Munnink B.B. AU - Cochrane, G. AU - Rahman, N. AU - Cummins, C. AU - Yuan, D.Y. AU - Selvakumar, S. AU - Mansurova, M. AU - O’Cathail, C. AU - Sokolov, A. AU - Thorne, R. AU - Worp, N. AU - Amid, C. AU - Csabai, István TI - Systematic detection of co-infection and intra-host recombination in more than 2 million global SARS-CoV-2 samples JF - NATURE COMMUNICATIONS J2 - NAT COMMUN VL - 15 PY - 2024 IS - 1 SN - 2041-1723 DO - 10.1038/s41467-023-43391-z UR - https://m2.mtmt.hu/api/publication/34525724 ID - 34525724 N1 - Department of Physics of Complex Systems, ELTE Eötvös Loránd University, Pázmány P. s. 1A, Budapest, 1117, Hungary Department of Viroscience, Erasmus University Medical Center, Rotterdam, Netherlands European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Cambridge, Hinxton, CB10 1SD, United Kingdom Export Date: 23 January 2024; Cited By: 0; Correspondence Address: A. Medgyes-Horváth; Department of Physics of Complex Systems, ELTE Eötvös Loránd University, Budapest, Pázmány P. s. 1A, 1117, Hungary; email: horvath.anna@ttk.elte.hu LA - English DB - MTMT ER - TY - JOUR AU - Barták, Barbara Kinga AU - Nagy, Zoltán AU - Farkas, Eszter Alexandra AU - Bányai, F AU - Szakállas, Nikolett AU - Valcz, Gábor AU - Pipek, Orsolya Anna AU - Csabai, István AU - Takács, István AU - Molnár, Béla TI - FOLSAV-PÓTLÁS HATÁSÁNAK VIZSGÁLATA HYPERHOMOCYSTEINAEMIÁBAN SZENVEDŐ IBD-S BETEGEKBEN JF - MAGYAR BELORVOSI ARCHIVUM J2 - MBA VL - 76 PY - 2023 IS - 5-6 SP - 300 EP - 300 PG - 1 SN - 0133-5464 UR - https://m2.mtmt.hu/api/publication/34558223 ID - 34558223 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Csende, Kristóf AU - Megyesfalvi, Zsolt AU - Ferencz, Bence AU - Fillinger, János AU - Poór, Valentin AU - Lantos, András AU - Pipek, Orsolya Anna AU - Sólyom-Tisza, Anna AU - Schelch, Karin AU - Bogos, Krisztina AU - Kocsis, Ákos AU - Agócs, László AU - Rényi-Vámos, Ferenc István AU - Lang, Christian AU - Schwendenwein, Anna AU - Boettiger, Kristiina AU - László, Viktória AU - Döme, Balázs AU - Berta, Judit TI - Immunológiai markerek expressziójának vizsgálata neuroendokrin tüdődaganatokban JF - MAGYAR ONKOLÓGIA J2 - MAGYAR ONKOLÓGIA VL - 67 PY - 2023 IS - 1. szupplementum SP - 18 EP - 18 PG - 1 SN - 0025-0244 UR - https://m2.mtmt.hu/api/publication/34326594 ID - 34326594 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Csaba, Márton AU - Radeczky, Péter AU - Ghimessy, Áron AU - Andi, Judit AU - Sinkovics, István AU - Pipek, Orsolya Anna AU - Megyesfalvi, Zsolt AU - Döme, Balázs AU - Rényi-Vámos, Ferenc István TI - Preoperatív lokalizációs módszerek hatékonyságának vizsgálata perifériás tüdőgócok esetén JF - MAGYAR ONKOLÓGIA J2 - MAGYAR ONKOLÓGIA VL - 67 PY - 2023 IS - 1. szupplementum SP - 18 EP - 18 PG - 1 SN - 0025-0244 UR - https://m2.mtmt.hu/api/publication/34326471 ID - 34326471 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Gyulai, Márton AU - Harko, Tunde AU - Fábián, Katalin AU - Karsko, Luca AU - Agócs, László AU - Szigeti, Balazs AU - Fillinger, János AU - Szállási, Zoltán AU - Pipek, Orsolya Anna AU - Moldvay, Judit TI - Claudin expression in pulmonary adenoid cystic carcinoma and mucoepidermoid carcinoma JF - PATHOLOGY AND ONCOLOGY RESEARCH J2 - PATHOL ONCOL RES VL - 29 PY - 2023 PG - 10 SN - 1219-4956 DO - 10.3389/pore.2023.1611328 UR - https://m2.mtmt.hu/api/publication/34091436 ID - 34091436 N1 - Összes idézések száma a WoS-ban: 0 AB - Background: Although the expression of tight junction protein claudins (CLDNs) is well known in common histological subtypes of lung cancer, it has not been investigated in rare lung cancers. The aim of our study was to examine the expression of different CLDNs in pulmonary salivary gland tumors. LA - English DB - MTMT ER - TY - JOUR AU - Ferencz, Bence AU - Megyesfalvi, Zsolt AU - Csende, Kristóf AU - Fillinger, János AU - Poór, Valentin AU - Lantos, András AU - Pipek, Orsolya Anna AU - Sólyom-Tisza, Anna AU - Rényi-Vámos, Ferenc István AU - Schelch, Karin AU - Lang, Christian AU - Schwendenwein, Anna AU - Boettiger, Kristiina AU - Laszlo, Viktoria AU - Hoetzenecker, Konrad AU - Döme, Balázs AU - Berta, Judit TI - Comparative expression analysis of immune-related markers in surgically resected lung neuroendocrine neoplasms JF - LUNG CANCER J2 - LUNG CANCER-J IASLC VL - 181 PY - 2023 PG - 14 SN - 0169-5002 DO - 10.1016/j.lungcan.2023.107263 UR - https://m2.mtmt.hu/api/publication/33999025 ID - 33999025 N1 - Funding Agency and Grant Number: Hungarian National Research, Development and Innovation Office; Austrian Science Fund [KH130356, KKP126790, 2020-1.1.6-JOVO, FK-143751, TKP2021-EGA-33]; Hungarian Respiratory Society (MPA) [FWF I3522, FWF I3977, I4677]; New National Excellence Program of the Ministry for Innovation and Technology of Hungary [2020]; IASLC/ILCF Young Investigator Grant 2022 [UNKP-20-3, UNKP-21-3]; Semmelweis 250 + Excellence PhD Scholarship of the Semmelweis University; Bolyai Research Scholarship of the Hungarian Academy of Sciences [EFOP- 3.6.3-VEKOP-16-2017-00009]; New National Excellence Program of the Ministry for Innovation and Technology; Austrian Science Fund (FWF) [UNKP-19-4]; City of Vienna Fund for Innovative Interdisciplinary Cancer Research [T 1062-B33] Funding text: BD, ZM, JB and FB acknowledge funding from the Hungarian National Research, Development and Innovation Office (KH130356 and KKP126790 to BD; 2020-1.1.6-JOVO & nbsp;and FK-143751 to BD and ZM, and TKP2021-EGA-33 to BD, ZM, JB and BF). BD was also supported by the Austrian Science Fund (FWF I3522, FWF I3977 and I4677). JB and ZM were supported by the Hungarian Respiratory Society (MPA #2020), and ZM by the UNKP-20-3 and UNKP-21-3 New National Excellence Program of the Ministry for Innovation and Technology of Hungary. ZM is recipient of the IASLC/ILCF Young Investigator Grant 2022. BF is a recipient of the Semmelweis 250 + Excellence PhD Scholarship (EFOP- 3.6.3-VEKOP-16-2017-00009) of the Semmelweis University. VL is a recipient of the Bolyai Research Scholarship of the Hungarian Academy of Sciences and the UNKP-19-4 New National Excellence Program of the Ministry for Innovation and Technology. KS was supported by the Austrian Science Fund (FWF No. T 1062-B33) and the City of Vienna Fund for Innovative Interdisciplinary Cancer Research. AB - Although immunotherapy has led to a paradigm shift in the treatment of lung cancer, the therapeutic approaches for lung neuroendocrine neoplasms (LNENs) are still limited. Our aim was to explore the immunological landscape and the expression of immune checkpoint markers in LNENs.Surgically removed tumor samples of 26 atypical carcinoid (AC), 30 large cell neuroendocrine carcinoma (LCNEC) and 29 small cell lung cancer (SCLC) patients were included. The immune phenotype of each tumor type was assessed by using a panel of 15 immune-related markers. As these markers are potentially expressed by immune cells and/or tumor cells, they might serve as putative targets for immunotherapy. Expression patterns were measured by immunohistochemistry and correlated with clinicopathological parameters and prognosis.Unsupervised hierarchical clustering revealed distinct immunologic profiles across tumor types. Specifically, AC tumors were characterized by high tumor cell CD40 expression and low levels of immune infiltrates whereas SCLC samples had a high CD47 and Inducible T Cell Costimulator (ICOS) expression in tumor cells and immune cells, respectively. High CD70 and CD137 expression by tumor cells as well as elevated expression of CD27, Lymphocyte Activation Gene 3 (LAG3), and CD40 by immune cells were characteristic for LCNEC samples. Overall, SCLC and LCNEC tumors had a more immunogenic phenotype than AC samples. High tumor cell CD47 and CD40 expressions were associated with impaired and improved survival outcomes, respectively.By providing insights into the widely divergent immunologic profiles of LNENs, our results might serve as a basis for the development of novel immunotherapy-related approaches in these devastating malignancies. LA - English DB - MTMT ER - TY - JOUR AU - Marx, Anita AU - Osváth, Magdolna AU - Szikora, Bence AU - Pipek, Orsolya Anna AU - Csabai, István AU - Nagy, Ákos AU - Bödör, Csaba AU - Matula, Zsolt AU - Nagy, Ginette AU - Bors, András AU - Uher, Ferenc AU - Mikala, Gábor AU - Vályi-Nagy, István AU - Kacskovics, Imre TI - Liquid biopsy-based monitoring of residual disease in multiple myeloma by analysis of the rearranged immunoglobulin genes–A feasibility study JF - PLOS ONE J2 - PLOS ONE VL - 18 PY - 2023 IS - 5 PG - 23 SN - 1932-6203 DO - 10.1371/journal.pone.0285696 UR - https://m2.mtmt.hu/api/publication/33893006 ID - 33893006 N1 - * Megosztott szerzőség AB - The need for sensitive monitoring of minimal/measurable residual disease (MRD) in multiple myeloma emerged as novel therapies led to deeper responses. Moreover, the potential benefits of blood-based analyses, the so-called liquid biopsy is prompting more and more studies to assess its feasibility. Considering these recent demands, we aimed to optimize a highly sensitive molecular system based on the rearranged immunoglobulin (Ig) genes to monitor MRD from peripheral blood. We analyzed a small group of myeloma patients with the high-risk t(4;14) translocation, using next-generation sequencing of Ig genes and droplet digital PCR of patient-specific Ig heavy chain (IgH) sequences. Moreover, well established monitoring methods such as multiparametric flow cytometry and RT-qPCR of the fusion transcript IgH :: MMSET (IgH and multiple myeloma SET domain-containing protein) were utilized to evaluate the feasibility of these novel molecular tools. Serum measurements of M-protein and free light chains together with the clinical assessment by the treating physician served as routine clinical data. We found significant correlation between our molecular data and clinical parameters, using Spearman correlations. While the comparisons of the Ig-based methods and the other monitoring methods (flow cytometry, qPCR) were not statistically evaluable, we found common trends in their target detection. Regarding longitudinal disease monitoring, the applied methods yielded complementary information thus increasing the reliability of MRD evaluation. We also detected indications of early relapse before clinical signs, although this implication needs further verification in a larger patient cohort. LA - English DB - MTMT ER - TY - JOUR AU - Pipek, Orsolya Anna AU - Alpár, Donát AU - Rusz, Orsolya AU - Bödör, Csaba AU - Udvarnoki, Zoltán András AU - Medgyes-Horváth, Anna AU - Csabai, István AU - Szállási, Zoltán AU - Madaras, Lilla AU - Kahán, Zsuzsanna AU - Cserni, Gábor AU - Kővári, Bence AU - Kulka, Janina AU - Tőkés, Anna-Mária TI - Genomic Landscape of Normal and Breast Cancer Tissues in a Hungarian Pilot Cohort JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 10 PG - 19 SN - 1661-6596 DO - 10.3390/ijms24108553 UR - https://m2.mtmt.hu/api/publication/33814839 ID - 33814839 N1 - Funding Agency and Grant Number: NKFIH, Hungary [FK20-134253, K21-137948, TKP2021-EGA-24, TKP2021-NVA-15, NVKP-16-1-2016-0004]; EU's Horizon 2020 research and innovation program [739593]; Janos Bolyai Research Scholarship program of the Hungarian Academy of Sciences [BO/00125/22]; New National Excellence Program of the Ministry for Innovation and Technology [UNKP-22-5-SE-7]; Complementary Research Excellence Program; Kerpel Talent Award of Semmelweis University [EFOP-3.6.3-VEKOP-16-2017-00009]; ELIXIR Hungary Funding text: This study was supported by the following grants: NKFIH, Hungary: FK20-134253, K21-137948, TKP2021-EGA-24, TKP2021-NVA-15 and NVKP-16-1-2016-0004. The study was also supported by the EU's Horizon 2020 research and innovation program (No. 739593), the Janos Bolyai Research Scholarship program (BO/00125/22) of the Hungarian Academy of Sciences, the UNKP-22-5-SE-7 grant of the New National Excellence Program of the Ministry for Innovation and Technology, by the Complementary Research Excellence Program, the Kerpel Talent Award of Semmelweis University (EFOP-3.6.3-VEKOP-16-2017-00009), and the ELIXIR Hungary. AB - A limited number of studies have focused on the mutational landscape of breast cancer in different ethnic populations within Europe and compared the data with other ethnic groups and databases. We performed whole-genome sequencing of 63 samples from 29 Hungarian breast cancer patients. We validated a subset of the identified variants at the DNA level using the Illumina TruSight Oncology (TSO) 500 assay. Canonical breast-cancer-associated genes with pathogenic germline mutations were CHEK2 and ATM. Nearly all the observed germline mutations were as frequent in the Hungarian breast cancer cohort as in independent European populations. The majority of the detected somatic short variants were single-nucleotide polymorphisms (SNPs), and only 8% and 6% of them were deletions or insertions, respectively. The genes most frequently affected by somatic mutations were KMT2C (31%), MUC4 (34%), PIK3CA (18%), and TP53 (34%). Copy number alterations were most common in the NBN, RAD51C, BRIP1, and CDH1 genes. For many samples, the somatic mutational landscape was dominated by mutational processes associated with homologous recombination deficiency (HRD). Our study, as the first breast tumor/normal sequencing study in Hungary, revealed several aspects of the significantly mutated genes and mutational signatures, and some of the copy number variations and somatic fusion events. Multiple signs of HRD were detected, highlighting the value of the comprehensive genomic characterization of breast cancer patient populations. LA - English DB - MTMT ER -