@article{MTMT:34839166, title = {Expression patterns of novel immunotherapy targets in intermediate- and high-grade lung neuroendocrine neoplasms}, url = {https://m2.mtmt.hu/api/publication/34839166}, author = {Ferencz, Bence and Török, Klára and Pipek, Orsolya Anna and Fillinger, János and Csende, Kristóf and Lantos, András and Černeková, Radoslava and Mitták, Marcel and Škarda, Jozef and Delongová, Patricie and Megyesfalvi, Evelyn and Schelch, Karin and Lang, Christian and Solta, Anna and Boettiger, Kristiina and Brcic, Luka and Lindenmann, Jörg and Rényi-Vámos, Ferenc István and Aigner, Clemens and Berta, Judit and Megyesfalvi, Zsolt and Döme, Balázs}, doi = {10.1007/s00262-024-03704-7}, journal-iso = {CANCER IMMUNOL IMMUN}, journal = {CANCER IMMUNOLOGY IMMUNOTHERAPY}, volume = {73}, unique-id = {34839166}, issn = {1432-0851}, abstract = {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.}, keywords = {immunohistochemistry; Immune phenotype; Immunotherapy target; Lung neuroendocrine neoplasm}, year = {2024}, eissn = {0340-7004}, pages = {114}, orcid-numbers = {Ferencz, Bence/0000-0001-9820-2441; Török, Klára/0000-0002-1122-7345; Pipek, Orsolya Anna/0000-0001-8109-0340; Csende, Kristóf/0000-0002-0403-1440; Megyesfalvi, Evelyn/0000-0002-1690-2450; Rényi-Vámos, Ferenc István/0000-0002-0555-2096; Megyesfalvi, Zsolt/0000-0001-8552-6500; Döme, Balázs/0000-0001-8799-8624} } @article{MTMT:34527502, title = {Biologically informed deep learning for explainable epigenetic clocks}, url = {https://m2.mtmt.hu/api/publication/34527502}, author = {Prosz, Aurel and Pipek, Orsolya Anna and Börcsök, Judit and Palla, Gergely and Szallasi, Zoltan and Spisák, Sándor and Csabai, István}, doi = {10.1038/s41598-023-50495-5}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {14}, unique-id = {34527502}, issn = {2045-2322}, abstract = {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.}, year = {2024}, eissn = {2045-2322}, orcid-numbers = {Pipek, Orsolya Anna/0000-0001-8109-0340; Palla, Gergely/0000-0002-3406-4200; Csabai, István/0000-0001-9232-9898} } @article{MTMT:34525724, title = {Systematic detection of co-infection and intra-host recombination in more than 2 million global SARS-CoV-2 samples}, url = {https://m2.mtmt.hu/api/publication/34525724}, author = {Pipek, Orsolya Anna and Medgyes-Horváth, Anna and Stéger, József and Papp, Krisztián and Visontai, David and Koopmans, M. and Nieuwenhuijse, D. and Oude, Munnink B.B. and Cochrane, G. and Rahman, N. and Cummins, C. and Yuan, D.Y. and Selvakumar, S. and Mansurova, M. and O’Cathail, C. and Sokolov, A. and Thorne, R. and Worp, N. and Amid, C. and Csabai, István}, doi = {10.1038/s41467-023-43391-z}, journal-iso = {NAT COMMUN}, journal = {NATURE COMMUNICATIONS}, volume = {15}, unique-id = {34525724}, issn = {2041-1723}, year = {2024}, eissn = {2041-1723}, orcid-numbers = {Pipek, Orsolya Anna/0000-0001-8109-0340; Medgyes-Horváth, Anna/0000-0003-4435-5797; Stéger, József/0000-0003-2836-1855; Papp, Krisztián/0000-0003-0619-8233; Visontai, David/0000-0002-0029-709X; Csabai, István/0000-0001-9232-9898} } @article{MTMT:34558223, title = {FOLSAV-PÓTLÁS HATÁSÁNAK VIZSGÁLATA HYPERHOMOCYSTEINAEMIÁBAN SZENVEDŐ IBD-S BETEGEKBEN}, url = {https://m2.mtmt.hu/api/publication/34558223}, author = {Barták, Barbara Kinga and Nagy, Zoltán and Farkas, Eszter Alexandra and Bányai, F and Szakállas, Nikolett and Valcz, Gábor and Pipek, Orsolya Anna and Csabai, István and Takács, István and Molnár, Béla}, journal-iso = {MBA}, journal = {MAGYAR BELORVOSI ARCHIVUM}, volume = {76}, unique-id = {34558223}, issn = {0133-5464}, year = {2023}, pages = {300-300}, orcid-numbers = {Nagy, Zoltán/0000-0002-6493-5601; Valcz, Gábor/0000-0002-7109-3529; Pipek, Orsolya Anna/0000-0001-8109-0340; Csabai, István/0000-0001-9232-9898; Takács, István/0000-0002-7810-4833; Molnár, Béla/0000-0001-6655-7942} } @article{MTMT:34326594, title = {Immunológiai markerek expressziójának vizsgálata neuroendokrin tüdődaganatokban}, url = {https://m2.mtmt.hu/api/publication/34326594}, author = {Csende, Kristóf and Megyesfalvi, Zsolt and Ferencz, Bence and Fillinger, János and Poór, Valentin and Lantos, András and Pipek, Orsolya Anna and Sólyom-Tisza, Anna and Schelch, Karin and Bogos, Krisztina and Kocsis, Ákos and Agócs, László and Rényi-Vámos, Ferenc István and Lang, Christian and Schwendenwein, Anna and Boettiger, Kristiina and László, Viktória and Döme, Balázs and Berta, Judit}, journal-iso = {MAGYAR ONKOLÓGIA}, journal = {MAGYAR ONKOLÓGIA}, volume = {67}, unique-id = {34326594}, issn = {0025-0244}, year = {2023}, eissn = {2060-0399}, pages = {18-18}, orcid-numbers = {Csende, Kristóf/0000-0002-0403-1440; Megyesfalvi, Zsolt/0000-0001-8552-6500; Ferencz, Bence/0000-0001-9820-2441; Pipek, Orsolya Anna/0000-0001-8109-0340; Sólyom-Tisza, Anna/0000-0001-5871-2930; Kocsis, Ákos/0000-0001-9751-0215; Agócs, László/0000-0002-5578-4100; Rényi-Vámos, Ferenc István/0000-0002-0555-2096; Döme, Balázs/0000-0001-8799-8624} } @article{MTMT:34326471, title = {Preoperatív lokalizációs módszerek hatékonyságának vizsgálata perifériás tüdőgócok esetén}, url = {https://m2.mtmt.hu/api/publication/34326471}, author = {Csaba, Márton and Radeczky, Péter and Ghimessy, Áron and Andi, Judit and Sinkovics, István and Pipek, Orsolya Anna and Megyesfalvi, Zsolt and Döme, Balázs and Rényi-Vámos, Ferenc István}, journal-iso = {MAGYAR ONKOLÓGIA}, journal = {MAGYAR ONKOLÓGIA}, volume = {67}, unique-id = {34326471}, issn = {0025-0244}, year = {2023}, eissn = {2060-0399}, pages = {18-18}, orcid-numbers = {Radeczky, Péter/0000-0001-5756-2328; Ghimessy, Áron/0000-0002-0385-1586; Sinkovics, István/0000-0001-6270-479X; Pipek, Orsolya Anna/0000-0001-8109-0340; Megyesfalvi, Zsolt/0000-0001-8552-6500; Döme, Balázs/0000-0001-8799-8624; Rényi-Vámos, Ferenc István/0000-0002-0555-2096} } @article{MTMT:34091436, title = {Claudin expression in pulmonary adenoid cystic carcinoma and mucoepidermoid carcinoma}, url = {https://m2.mtmt.hu/api/publication/34091436}, author = {Gyulai, Márton and Harko, Tunde and Fábián, Katalin and Karsko, Luca and Agócs, László and Szigeti, Balazs and Fillinger, János and Szállási, Zoltán and Pipek, Orsolya Anna and Moldvay, Judit}, doi = {10.3389/pore.2023.1611328}, journal-iso = {PATHOL ONCOL RES}, journal = {PATHOLOGY AND ONCOLOGY RESEARCH}, volume = {29}, unique-id = {34091436}, issn = {1219-4956}, abstract = {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.}, year = {2023}, eissn = {1532-2807}, orcid-numbers = {Agócs, László/0000-0002-5578-4100; Szállási, Zoltán/0000-0001-5395-7509; Pipek, Orsolya Anna/0000-0001-8109-0340} } @article{MTMT:33999025, title = {Comparative expression analysis of immune-related markers in surgically resected lung neuroendocrine neoplasms}, url = {https://m2.mtmt.hu/api/publication/33999025}, author = {Ferencz, Bence and Megyesfalvi, Zsolt and Csende, Kristóf and Fillinger, János and Poór, Valentin and Lantos, András and Pipek, Orsolya Anna and Sólyom-Tisza, Anna and Rényi-Vámos, Ferenc István and Schelch, Karin and Lang, Christian and Schwendenwein, Anna and Boettiger, Kristiina and Laszlo, Viktoria and Hoetzenecker, Konrad and Döme, Balázs and Berta, Judit}, doi = {10.1016/j.lungcan.2023.107263}, journal-iso = {LUNG CANCER-J IASLC}, journal = {LUNG CANCER}, volume = {181}, unique-id = {33999025}, issn = {0169-5002}, abstract = {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.}, keywords = {immunohistochemistry; Immune-related markers; Immune phenotype; lung neuroendocrine tumors}, year = {2023}, eissn = {1872-8332}, orcid-numbers = {Ferencz, Bence/0000-0001-9820-2441; Megyesfalvi, Zsolt/0000-0001-8552-6500; Csende, Kristóf/0000-0002-0403-1440; Pipek, Orsolya Anna/0000-0001-8109-0340; Sólyom-Tisza, Anna/0000-0001-5871-2930; Rényi-Vámos, Ferenc István/0000-0002-0555-2096; Döme, Balázs/0000-0001-8799-8624} } @article{MTMT:33893006, title = {Liquid biopsy-based monitoring of residual disease in multiple myeloma by analysis of the rearranged immunoglobulin genes–A feasibility study}, url = {https://m2.mtmt.hu/api/publication/33893006}, author = {Marx, Anita and Osváth, Magdolna and Szikora, Bence and Pipek, Orsolya Anna and Csabai, István and Nagy, Ákos and Bödör, Csaba and Matula, Zsolt and Nagy, Ginette and Bors, András and Uher, Ferenc and Mikala, Gábor and Vályi-Nagy, István and Kacskovics, Imre}, doi = {10.1371/journal.pone.0285696}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {18}, unique-id = {33893006}, issn = {1932-6203}, abstract = {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.}, keywords = {multiple myeloma; liquid biopsy; circulating tumor DNA; next-generation sequencing (NGS); Circulating tumor cells; minimal residual disease (MRD); Droplet digital PCR (ddPCR); immunoglobulin genes}, year = {2023}, eissn = {1932-6203}, orcid-numbers = {Marx, Anita/0000-0001-8969-5766; Szikora, Bence/0000-0002-0766-5684; Pipek, Orsolya Anna/0000-0001-8109-0340; Csabai, István/0000-0001-9232-9898; Bödör, Csaba/0000-0002-0729-692X; Bors, András/0000-0003-2109-4678; Uher, Ferenc/0000-0001-7997-6142; Kacskovics, Imre/0000-0002-0402-3862} } @article{MTMT:33814839, title = {Genomic Landscape of Normal and Breast Cancer Tissues in a Hungarian Pilot Cohort}, url = {https://m2.mtmt.hu/api/publication/33814839}, author = {Pipek, Orsolya Anna and Alpár, Donát and Rusz, Orsolya and Bödör, Csaba and Udvarnoki, Zoltán András and Medgyes-Horváth, Anna and Csabai, István and Szállási, Zoltán and Madaras, Lilla and Kahán, Zsuzsanna and Cserni, Gábor and Kővári, Bence and Kulka, Janina and Tőkés, Anna-Mária}, doi = {10.3390/ijms24108553}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {24}, unique-id = {33814839}, issn = {1661-6596}, abstract = {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.}, year = {2023}, eissn = {1422-0067}, orcid-numbers = {Pipek, Orsolya Anna/0000-0001-8109-0340; Rusz, Orsolya/0000-0001-5726-4072; Bödör, Csaba/0000-0002-0729-692X; Udvarnoki, Zoltán András/0000-0001-7086-235X; Medgyes-Horváth, Anna/0000-0003-4435-5797; Csabai, István/0000-0001-9232-9898; Szállási, Zoltán/0000-0001-5395-7509; Madaras, Lilla/0000-0002-4137-4696; Kahán, Zsuzsanna/0000-0002-5021-8775; Cserni, Gábor/0000-0003-1344-7744; Kővári, Bence/0000-0002-4498-8781; Kulka, Janina/0000-0001-6498-5943; Tőkés, Anna-Mária/0000-0002-9581-7536} }