@article{MTMT:34850804,
	title = {T-reg transcriptomic signatures identify response to check-point inhibitors},
	url = {https://m2.mtmt.hu/api/publication/34850804},
	author = {Noblejas-López, M.D.M. and García-Gil, E. and Pérez-Segura, P. and Pandiella, A. and Győrffy, Balázs and Ocaña, A.},
	doi = {10.1038/s41598-024-60819-8},
	journal-iso = {SCI REP},
	journal = {SCIENTIFIC REPORTS},
	volume = {14},
	unique-id = {34850804},
	issn = {2045-2322},
	year = {2024},
	eissn = {2045-2322},
	orcid-numbers = {Győrffy, Balázs/0000-0002-5772-3766}
}

@misc{MTMT:34842721,
	title = {Predicting immune checkpoint therapy response in three independent metastatic melanoma cohorts},
	url = {https://m2.mtmt.hu/api/publication/34842721},
	author = {Leticia, Szadai and Aron, Bartha and Indira, Pla Parada and Lakatos, Alexandra and Pál, Dorottya and Anna, Sára Lengyel and Natália, Pinto de Almeida and Ágnes, Judit Jánosi and Fábio, Nogueira and Beata, Szeitz and Viktória, Doma and Nicole, Woldmar and Jéssica, Guedes and Zsuzsanna, Ujfaludi and Zoltán, Gábor Pahi and Pankotai, Tibor and Yonghyo, Kim and Győrffy, Balázs and Bo, Baldetorp and Charlotte, Welinder and A., Marcell Szasz and Lazaro, Betancourt and Jeovanis, Gil and Roger, Appelqvist and Ho-Jeong, Kwon and Sarolta, Kárpáti and Magdalena, Kuras and Jimmy, Rodriguez Murillo and István, Balázs Németh and Johan, Malm and David, Fenyö and Krzysztof, Pawłowski and Peter, Horvatovich and Elisabet, Wieslander and Kemény, Lajos Vince and Gilberto, Domont and György, MarkoVarga and Aniel, Sanchez},
	unique-id = {34842721},
	year = {2024},
	orcid-numbers = {Pál, Dorottya/0000-0002-9426-487X; Pankotai, Tibor/0000-0001-9810-5465; Győrffy, Balázs/0000-0002-5772-3766; Kemény, Lajos Vince/0000-0002-8233-1844}
}

@article{MTMT:34831592,
	title = {Integrated analysis of public datasets for the discovery and validation of survival-associated genes in solid tumors},
	url = {https://m2.mtmt.hu/api/publication/34831592},
	author = {Győrffy, Balázs},
	doi = {10.1016/j.xinn.2024.100625},
	journal-iso = {INNOVATION(UNITED STATES)},
	journal = {INNOVATION(UNITED STATES)},
	volume = {5},
	unique-id = {34831592},
	year = {2024},
	eissn = {2666-6758},
	orcid-numbers = {Győrffy, Balázs/0000-0002-5772-3766}
}

@article{MTMT:34828997,
	title = {Comprehensive analysis of differentially expressed miRNAs in hepatocellular carcinoma: Prognostic, predictive significance and pathway insights},
	url = {https://m2.mtmt.hu/api/publication/34828997},
	author = {Smith, K. and Beach, D. and Silva, R. and Győrffy, Balázs and Salani, F. and Crea, F.},
	doi = {10.1371/journal.pone.0296198},
	journal-iso = {PLOS ONE},
	journal = {PLOS ONE},
	volume = {19},
	unique-id = {34828997},
	issn = {1932-6203},
	year = {2024},
	eissn = {1932-6203},
	orcid-numbers = {Győrffy, Balázs/0000-0002-5772-3766}
}

@article{MTMT:34825015,
	title = {Prognostic significance of a signature based on senescence-related genes in colorectal cancer},
	url = {https://m2.mtmt.hu/api/publication/34825015},
	author = {Ungvári, Zoltán István and Ungvári, Anna Sára and Bianchini, Giampaolo and Győrffy, Balázs},
	doi = {10.1007/s11357-024-01164-6},
	journal-iso = {GEROSCIENCE},
	journal = {GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE)},
	unique-id = {34825015},
	issn = {2509-2715},
	abstract = {Colorectal cancer, recognized as a quintessential age-related disease, underscores the intricate interplay between aging mechanisms and disease pathogenesis. Cellular senescence, a DNA damage-induced cellular stress response, is characterized by cell cycle arrest, the expression of an inflammatory senescence-associated secretory phenotype, and alterations in extracellular matrix metabolism. It is widely recognized as a fundamental and evolutionarily conserved mechanism of aging. Guided by geroscience principles, which assert that the pathogenesis of age-related diseases involves cellular mechanisms of aging, this study delves into the role of senescence-related genes in colon cancer progression. Leveraging a gene set reflective of senescence-associated pathways, we employed uni- and multivariate Cox proportional hazards survival analysis combined with the determination of the false discovery rate to analyze correlations between gene expression and survival. The integrated database of 1130 colon cancer specimens with available relapse-free survival time and relapse event data from ten independent cohorts provided a robust platform for survival analyses. We identified senescence-related genes associated with differential expression levels linked to shorter survival. Our findings unveil a prognostic signature utilizing cellular senescence-related genes (hazard ratio: 2.73, 95% CI 2.12-3.52, p = 6.4E - 16), offering valuable insights into survival prediction in colon cancer. Multivariate analysis underscored the independence of the senescence-related signature from available epidemiological and pathological variables. This study highlights the potential of senescence-related genes as prognostic biomarkers. Overall, our results underscore the pivotal role of cellular senescence, a fundamental mechanism of aging, in colon cancer progression.},
	keywords = {CANCER; Aging; colorectal cancer; senescence; Gerooncology},
	year = {2024},
	eissn = {2509-2723},
	orcid-numbers = {Ungvári, Zoltán István/0000-0002-6035-6039; Győrffy, Balázs/0000-0002-5772-3766}
}

@article{MTMT:34825014,
	title = {Transient loss of Polycomb components induces an epigenetic cancer fate},
	url = {https://m2.mtmt.hu/api/publication/34825014},
	author = {Parreno, V and Loubiere, V and Schuettengruber, B and Fritsch, L and Rawal, C C and Erokhin, M and Győrffy, Balázs and Normanno, D and Di Stefano, M and Moreaux, J and Butova, N L and Chiolo, I and Chetverina, D and Martinez, A-M and Cavalli, G},
	doi = {10.1038/s41586-024-07328-w},
	journal-iso = {NATURE},
	journal = {NATURE},
	unique-id = {34825014},
	issn = {0028-0836},
	abstract = {Although cancer initiation and progression are generally associated with the accumulation of somatic mutations1,2, substantial epigenomic alterations underlie many aspects of tumorigenesis and cancer susceptibility3-6, suggesting that genetic mechanisms might not be the only drivers of malignant transformation7. However, whether purely non-genetic mechanisms are sufficient to initiate tumorigenesis irrespective of mutations has been unknown. Here, we show that a transient perturbation of transcriptional silencing mediated by Polycomb group proteins is sufficient to induce an irreversible switch to a cancer cell fate in Drosophila. This is linked to the irreversible derepression of genes that can drive tumorigenesis, including members of the JAK-STAT signalling pathway and zfh1, the fly homologue of the ZEB1 oncogene, whose aberrant activation is required for Polycomb perturbation-induced tumorigenesis. These data show that a reversible depletion of Polycomb proteins can induce cancer in the absence of driver mutations, suggesting that tumours can emerge through epigenetic dysregulation leading to inheritance of altered cell fates.},
	year = {2024},
	eissn = {1476-4687},
	orcid-numbers = {Győrffy, Balázs/0000-0002-5772-3766}
}

@article{MTMT:34804924,
	title = {In Silico Transcriptomic Expression of MSR1 in Solid Tumors Is Associated with Responses to Anti-PD1 and Anti-CTLA4 Therapies},
	url = {https://m2.mtmt.hu/api/publication/34804924},
	author = {Adrian, Sanvicente and Cristina, Diaz-Tejeiro and Cristina, Nieto-Jimenez and Lucia, Paniagua-Herranz and Igor Lopez, Cade and Győrffy, Balázs and Victor, Moreno and Pedro, Perez-Segura and Emiliano, Calvo and Alberto, Ocana},
	doi = {10.3390/ijms25073987},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {25},
	unique-id = {34804924},
	issn = {1661-6596},
	abstract = {Immuno-oncology has gained momentum with the approval of antibodies with clinical activities in different indications. Unfortunately, for anti-PD (L)1 agents in monotherapy, only half of the treated population achieves a clinical response. For other agents, such as anti-CTLA4 antibodies, no biomarkers exist, and tolerability can limit administration. In this study, using publicly available genomic datasets, we evaluated the expression of the macrophage scavenger receptor-A (SR-A) (MSR1) and its association with a response to check-point inhibitors (CPI). MSR1 was associated with the presence of macrophages, dendritic cells (DCs) and neutrophils in most of the studied indications. The presence of MSR1 was associated with macrophages with a pro-tumoral phenotype and correlated with TIM3 expression. MSR1 predicted favorable overall survival in patients treated with anti-PD1 (HR: 0.56, FDR: 1%, p = 2.6 x 10-5), anti PD-L1 (HR: 0.66, FDR: 20%, p = 0.00098) and anti-CTLA4 (HR: 0.37, FDR: 1%, p = 4.8 x 10-5). When specifically studying skin cutaneous melanoma (SKCM), we observed similar effects for anti-PD1 (HR: 0.65, FDR: 50%, p = 0.0072) and anti-CTLA4 (HR: 0.35, FDR: 1%, p = 4.1 x 10-5). In a different dataset of SKCM patients, the expression of MSR1 predicted a clinical response to anti-CTLA4 (AUC: 0.61, p = 2.9 x 10-2). Here, we describe the expression of MSR1 in some solid tumors and its association with innate cells and M2 phenotype macrophages. Of note, the presence of MSR1 predicted a response to CPI and, particularly, anti-CTLA4 therapies in different cohorts of patients. Future studies should prospectively explore the association of MSR1 expression and the response to anti-CTLA4 strategies in solid tumors.},
	keywords = {LOW-DENSITY-LIPOPROTEIN; PROGNOSTIC IMPACT; M2 macrophages; Biochemistry & Molecular Biology; Scavenger receptors; Anti-CTLA4; Anti-PD1; CD204-POSITIVE MACROPHAGES; MSR1},
	year = {2024},
	eissn = {1422-0067},
	orcid-numbers = {Győrffy, Balázs/0000-0002-5772-3766; Alberto, Ocana/0000-0002-1067-9630}
}

@article{MTMT:34763944,
	title = {Long-term Multimodal Recording Reveals Epigenetic Adaptation Routes in Dormant Breast Cancer Cells},
	url = {https://m2.mtmt.hu/api/publication/34763944},
	author = {Rosano, Dalia and Sofyali, Emre and Dhiman, Heena and Ghirardi, Chiara and Ivanoiu, Diana and Heide, Timon and Vingiani, Andrea and Bertolotti, Alessia and Pruneri, Giancarlo and Canale, Eleonora and Dewhurst, Hannah F and Saha, Debjani and Slaven, Neil and Barozzi, Iros and Li, Tong and Zemlyanskiy, Grigory and Phillips, Henry and James, Chela and Győrffy, Balázs and Lynn, Claire and Cresswell, George D and Rehman, Farah and Noberini, Roberta and Bonaldi, Tiziana and Sottoriva, Andrea and Magnani, Luca},
	doi = {10.1158/2159-8290.CD-23-1161},
	journal-iso = {CANCER DISCOV},
	journal = {CANCER DISCOVERY},
	volume = {14},
	unique-id = {34763944},
	issn = {2159-8274},
	abstract = {Patients with estrogen receptor-positive breast cancer receive adjuvant endocrine therapies (ET) that delay relapse by targeting clinically undetectable micrometastatic deposits. Yet, up to 50% of patients relapse even decades after surgery through unknown mechanisms likely involving dormancy. To investigate genetic and transcriptional changes underlying tumor awakening, we analyzed late relapse patients and longitudinally profiled a rare cohort treated with long-term neoadjuvant ETs until progression. Next, we developed an in vitro evolutionary study to record the adaptive strategies of individual lineages in unperturbed parallel experiments. Our data demonstrate that ETs induce nongenetic cell state transitions into dormancy in a stochastic subset of cells via epigenetic reprogramming. Single lineages with divergent phenotypes awaken unpredictably in the absence of recurrent genetic alterations. Targeting the dormant epigenome shows promising activity against adapting cancer cells. Overall, this study uncovers the contribution of epigenetic adaptation to the evolution of resistance to ETs.This study advances the understanding of therapy-induced dormancy with potential clinical implications for breast cancer. Estrogen receptor-positive breast cancer cells adapt to endocrine treatment by entering a dormant state characterized by strong heterochromatinization with no recurrent genetic changes. Targeting the epigenetic rewiring impairs the adaptation of cancer cells to ETs.},
	year = {2024},
	eissn = {2159-8290},
	pages = {866-889},
	orcid-numbers = {Győrffy, Balázs/0000-0002-5772-3766}
}

@article{MTMT:34725864,
	title = {Genomic and Immunologic Correlates in Prostate Cancer with High Expression of KLK2},
	url = {https://m2.mtmt.hu/api/publication/34725864},
	author = {Paniagua-Herranz, Lucía and Moreno, Irene and Nieto-Jiménez, Cristina and Garcia-Lorenzo, Esther and Díaz-Tejeiro, Cristina and Sanvicente, Adrián and Doger, Bernard and Pedregal, Manuel and Ramón, Jorge and Bartolomé, Jorge and Manzano, Arancha and Győrffy, Balázs and Gutierrez-Uzquiza, Álvaro and Pérez Segura, Pedro and Calvo, Emiliano and Moreno, Víctor and Ocana, Alberto},
	doi = {10.3390/ijms25042222},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {25},
	unique-id = {34725864},
	issn = {1661-6596},
	abstract = {The identification of surfaceome proteins is a main goal in cancer research to design antibody-based therapeutic strategies. T cell engagers based on KLK2, a kallikrein specifically expressed in prostate cancer (PRAD), are currently in early clinical development. Using genomic information from different sources, we evaluated the immune microenvironment and genomic profile of prostate tumors with high expression of KLK2. KLK2 was specifically expressed in PRAD but it was not significant associated with Gleason score. Additionally, KLK2 expression did not associate with the presence of any immune cell population and T cell activating markers. A mild correlation between the high expression of KLK2 and the deletion of TMPRSS2 was identified. KLK2 expression associated with high levels of surface proteins linked with a detrimental response to immune checkpoint inhibitors (ICIs) including CHRNA2, FAM174B, OR51E2, TSPAN1, PTPRN2, and the non-surface protein TRPM4. However, no association of these genes with an outcome in PRAD was observed. Finally, the expression of these genes in PRAD did not associate with an outcome in PRAD and any immune populations. We describe the immunologic microenvironment on PRAD tumors with a high expression of KLK2, including a gene signature linked with an inert immune microenvironment, that predicts the response to ICIs in other tumor types. Strategies targeting KLK2 with T cell engagers or antibody-drug conjugates will define whether T cell mobilization or antigen release and stimulation of immune cell death are sufficient effects to induce clinical activity.},
	keywords = {Prostate cancer; surfaceome; Immunologic profile; KLK2; T cell engagers},
	year = {2024},
	eissn = {1422-0067},
	orcid-numbers = {Győrffy, Balázs/0000-0002-5772-3766}
}

@article{MTMT:34561052,
	title = {Resistance to Combined Anthracycline–Taxane Chemotherapy Is Associated with Altered Metabolism and Inflammation in Breast Carcinomas},
	url = {https://m2.mtmt.hu/api/publication/34561052},
	author = {Menyhart, Otilia and Fekete, János Tibor and Győrffy, Balázs},
	doi = {10.3390/ijms25021063},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {25},
	unique-id = {34561052},
	issn = {1661-6596},
	abstract = {Approximately 30% of early-stage breast cancer (BC) patients experience recurrence after systemic chemotherapy; thus, understanding therapy resistance is crucial in developing more successful treatments. Here, we investigated the mechanisms underlying resistance to combined anthracycline–taxane treatment by comparing gene expression patterns with subsequent therapeutic responses. We established a cohort of 634 anthracycline–taxane-treated patients with pathological complete response (PCR) and a separate cohort of 187 patients with relapse-free survival (RFS) data, each having transcriptome-level expression data of 10,017 unique genes. Patients were categorized as responders and non-responders based on their PCR and RFS status, and the expression for each gene was compared between the two groups using a Mann–Whitney U-test. Statistical significance was set at p < 0.05, with fold change (FC) > 1.44. Altogether, 224 overexpressed genes were identified in the tumor samples derived from the patients without PCR; among these, the gene sets associated with xenobiotic metabolism (e.g., CYP3A4, CYP2A6) exhibited significant enrichment. The genes ORAI3 and BCAM differentiated non-responders from responders with the highest AUC values (AUC > 0.75, p < 0.0001). We identified 51 upregulated genes in the tumor samples derived from the patients with relapse within 60 months, participating primarily in inflammation and innate immune responses (e.g., LYN, LY96, ANXA1). Furthermore, the amino acid transporter SLC7A5, distinguishing non-responders from responders, had significantly higher expression in tumors and metastases than in normal tissues (Kruskal–Wallis p = 8.2 × 10−20). The identified biomarkers underscore the significance of tumor metabolism and microenvironment in treatment resistance and can serve as a foundation for preclinical validation studies. © 2024 by the authors.},
	keywords = {Inflammation; Inflammation; Inflammation; Humans; GENETICS; human; Drug Therapy, Combination; Antibiotics, Antineoplastic; Anthracyclines; anthracycline; anthracycline; Neoplasm Recurrence, Local; therapy resistance; tumor recurrence; Drug therapy; Taxoids; taxoid; antineoplastic antibiotic; bridged compound; Tumor microenvironment; Tumor microenvironment; combination drug therapy; Innate immune response; taxane; taxane; Bridged-Ring Compounds; inflammatory breast cancer; breast cancer (BC); inflammatory breast neoplasms},
	year = {2024},
	eissn = {1422-0067},
	orcid-numbers = {Menyhart, Otilia/0000-0003-4129-4589; Fekete, János Tibor/0000-0002-6672-6563; Győrffy, Balázs/0000-0002-5772-3766}
}