@article{MTMT:35447386,
	title = {Overweight and obesity significantly increase colorectal cancer risk: a meta-analysis of 66 studies revealing a 25–57% elevation in risk},
	url = {https://m2.mtmt.hu/api/publication/35447386},
	author = {Ungvári, Zoltán István and Fekete, Mónika and Varga, Péter and Lehoczki, Andrea Marianna and Fekete, János Tibor and Ungvári, Anna Sára and Győrffy, Balázs},
	doi = {10.1007/s11357-024-01375-x},
	journal-iso = {GEROSCIENCE},
	journal = {GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE)},
	volume = {In press},
	unique-id = {35447386},
	issn = {2509-2715},
	abstract = {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.},
	year = {2024},
	eissn = {2509-2723},
	pages = {In press},
	orcid-numbers = {Ungvári, Zoltán István/0000-0002-6035-6039; Fekete, Mónika/0000-0001-8632-2120; Fekete, János Tibor/0000-0002-6672-6563; Győrffy, Balázs/0000-0002-5772-3766}
}

@article{MTMT:35427260,
	title = {The Immune-Related 27-Gene Signature DetermaIO Predicts Response to Neoadjuvant Atezolizumab plus Chemotherapy in Triple-Negative Breast Cancer.},
	url = {https://m2.mtmt.hu/api/publication/35427260},
	author = {Dugo, Matteo and Huang, Chiun-Sheng and Egle, Daniel and Bermejo, Begoña and Zamagni, Claudio and Seitz, Robert S and Nielsen, Tyler J and Thill, Marc and Antón-Torres, Antonio and Russo, Stefania and Ciruelos, Eva Maria and Schweitzer, Brock L and Ross, Douglas T and Galbardi, Barbara and Greil, Richard and Semiglazov, Vladimir and Győrffy, Balázs and Colleoni, Marco and Kelly, Catherine M and Mariani, Gabriella and Del Mastro, Lucia and Blasi, Olivia and Callari, Maurizio and Pusztai, Lajos and Valagussa, Pinuccia and Viale, Giuseppe and Gianni, Luca and Bianchini, Giampaolo},
	doi = {10.1158/1078-0432.CCR-24-0149},
	journal-iso = {CLIN CANCER RES},
	journal = {CLINICAL CANCER RESEARCH},
	unique-id = {35427260},
	issn = {1078-0432},
	abstract = {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.},
	year = {2024},
	eissn = {1557-3265},
	orcid-numbers = {Győrffy, Balázs/0000-0002-5772-3766}
}

@article{MTMT:35309371,
	title = {A Functional Survey of the Regulatory Landscape of Estrogen Receptor-Positive Breast Cancer Evolution},
	url = {https://m2.mtmt.hu/api/publication/35309371},
	author = {Barozzi, I. and Slaven, N. and Canale, E. and Lopes, R. and Amorim, Monteiro Barbosa I. and Bleu, M. and Ivanoiu, D. and Pacini, C. and Mensa', E. and Chambers, A. and Bravaccini, S. and Ravaioli, S. and Győrffy, Balázs and Dieci, M.V. and Pruneri, G. and Galli, G.G. and Magnani, L.},
	doi = {10.1158/2159-8290.CD-23-1157},
	journal-iso = {CANCER DISCOV},
	journal = {CANCER DISCOVERY},
	volume = {14},
	unique-id = {35309371},
	issn = {2159-8274},
	year = {2024},
	eissn = {2159-8290},
	pages = {1612-1630},
	orcid-numbers = {Győrffy, Balázs/0000-0002-5772-3766}
}

@misc{MTMT:35262423,
	title = {Predicting immune checkpoint therapy response in three independent metastatic melanoma cohorts},
	url = {https://m2.mtmt.hu/api/publication/35262423},
	author = {Szadai, Leticia and Bartha, Áron and Pla, Parada Indira and Lakatos, Alexandra and Pál, Dorottya and Lengyel, Anna Sára and Pinto, de Almeida Natália and Jánosi, Ágnes Judit and Nogueira, Fábio and Szeitz, Beáta and Doma, Viktória and Woldmar, Nicole and Guedes, Jéssica and Újfaludi, Zsuzsanna and Páhi, Zoltán Gábor and Pankotai, Tibor and Kim, Yonghyo and Győrffy, Balázs and Baldetorp, Bo and Welinder, Charlotte and Szász, Attila Marcell and Betancourt, Lazaro and Gil, Jeovanis and Appelqvist, Roger and Kwon, Ho-Jeong and Kárpáti, Sarolta and Kuras, Magdalena and Rodriguez, Murillo Jimmy and Németh, István Balázs and Malm, Johan and Fenyö, David and Pawłowski, Krzysztof and Horvatovich, Peter and Wieslander, Elisabet and Kemény, Lajos Vince and Domont, Gilberto and Marko-Varga, György and Sanchez, Aniel},
	doi = {10.1101/2024.05.01.592032},
	unique-id = {35262423},
	year = {2024},
	orcid-numbers = {Pál, Dorottya/0000-0002-9426-487X; Szeitz, Beáta/0000-0001-6414-0537; Újfaludi, Zsuzsanna/0000-0003-4738-0963; Páhi, Zoltán Gábor/0000-0002-3428-553X; Pankotai, Tibor/0000-0001-9810-5465; Győrffy, Balázs/0000-0002-5772-3766; Szász, Attila Marcell/0000-0003-2739-4196; Kárpáti, Sarolta/0000-0002-8472-0712; Kemény, Lajos Vince/0000-0002-8233-1844}
}

@CONFERENCE{MTMT:35208573,
	title = {RNA degradation in human brain tissue samples depends on multiple factors},
	url = {https://m2.mtmt.hu/api/publication/35208573},
	author = {Dobolyiné Renner, Éva and Dóra, Fanni and Munkácsy, Gyöngyi and Dóczi, Tamás Péter and Győrffy, Balázs and Dobolyi, Árpád and Palkovits, Miklós},
	booktitle = {International Neuroscience Conference, Pécs 2024},
	unique-id = {35208573},
	abstract = {Recent developments in RNA sequencing increased the use of human brain tissue samples in understanding transcriptional alterations in neurological and psychiatric diseases. The human brain tissue samples typically cannot be processed immediately for RNA isolation. Rather, the dissection of the brain is usually carried out hours after the death is confirmed. Subsequently, the brains are stored frozen or in fixative before dissection of RNA. Even the rare surgical samples cannot be processed on the site and need to be transported to a laboratory for RNA isolation. RNA is not stable as it can be degraded by RNases as well as its chemical decomposition can happen. These processes depend on the microenvironment around the RNA, which may not be the same for the different samples. Therefore, in the present study, we aimed to examine RNA quality in different human brain samples stored in the Human Brain Tissue Bank of the Semmelweis University. RNA quality was assessed by measuring the RNA integrity number (RIN) following an RNA purification protocol combining the Trizol method and the columnar purification steps. RNA quality varied depending on the brain, which the samples were dissected from. The position of the brain tissue sample within the brain had less effect on the RNA quality. Interestingly, once the RNA quality was good in a particular brain, it remained stable for several hours and showed only limited degradation with postmortem time (2 to 10 hours at room temperature). In contrast, neurosurgical samples (brain tissue removed from the brain during neurosurgery), which have a small size, showed fast degradation if stored at room temperature for 1 min to 3 hours. In addition to these factors, the RNA quality also showed some dependency on the types of disease the patient suffered from. In contrast, sex and age dependence was not found. These data suggest that the brains have to be tested for RNA quality and dissections for transcriptomics have to be performed only from selected brains with high RIN numbers. In turn, a good quality RNA (better than RIN number 7) can be obtained from many brains stored at -80 °C if properly processed.
		
		Grant support was provided by HAS NAP2022-I-3/2022 and NAP2022-I-4/2022 NAP3 of the Hungarian Academy of Sciences, EFOP-3.6.3-VEKOP-16-2017-00009 and Thematic Excellence Program of the Semmelweis University.},
	year = {2024},
	pages = {285-285},
	orcid-numbers = {Dóra, Fanni/0000-0001-8301-8203; Munkácsy, Gyöngyi/0000-0001-9124-4788; Győrffy, Balázs/0000-0002-5772-3766; Dobolyi, Árpád/0000-0003-0397-2991; Palkovits, Miklós/0000-0003-0578-0387}
}

@article{MTMT:35195205,
	title = {LPA suppresses HLA-DR expression in human melanoma cells: a potential immune escape mechanism involving LPAR1 and DR6-mediated release of IL-10},
	url = {https://m2.mtmt.hu/api/publication/35195205},
	author = {Major, Enikő and Lin, Kuan-Hung and Lee, Sue Chin and Káldi, Krisztina and Győrffy, Balázs and Tigyi, Gabor and Benyó, Zoltán},
	doi = {10.1038/s41401-024-01373-x},
	journal-iso = {ACTA PHARMACOL SIN},
	journal = {ACTA PHARMACOLOGICA SINICA},
	volume = {2024},
	unique-id = {35195205},
	issn = {1671-4083},
	abstract = {While immune checkpoint inhibitors (ICIs) are promising in the treatment of metastatic melanoma, about half of patients do not respond well to them. Low levels of human leukocyte antigen-DR (HLA-DR) in tumors have been shown to negatively influence prognosis and response to ICIs. Lysophosphatidic acid (LPA) is produced in large amounts by melanoma and is abundantly present in the tumor microenvironment. LPA induces the release of various cytokines and chemokines from tumor cells, which affect cancer development, metastasis, and tumor immunity. In the present study, we investigated the role of LPA-induced IL-10 release in regulating HLA-DR expression and the underlying mechanisms in human melanoma cells. We showed that LPA (0.001–10 μM) dose-dependently increased DR6 transcript levels through activating LPAR1 in HEK293T cells. Knockdown of NF-κB1 abrogated the LPA-increased DR6 expression without affecting basal DR6 expression in both A2058 and A375 melanoma cell lines. LPA (10 µM) significantly increased IL-10 transcripts in A2058 and A375 melanoma cells, the effect was abolished by pharmacological inhibition of LPAR1 or knockdown of DR6. We found a statistically significant correlation between the expression of LPAR1, DR6 and IL-10 in human melanoma tissue and an association between increased expression of LPAR1 and reduced effectiveness of ICI therapy. We demonstrated that LPA (10 µM) markedly suppressed HLA-DR expression in both A375 and A2058 melanoma cells via activating the LPAR1-DR6-IL-10 pathway. These data suggest that the LPAR1-DR6-IL-10 autocrine loop could constitute a novel mechanism used by tumor cells to evade immunosurveillance by decreasing HLA-DR expression.},
	year = {2024},
	eissn = {1745-7254},
	orcid-numbers = {Major, Enikő/0000-0001-5854-9395; Káldi, Krisztina/0000-0002-5724-0182; Győrffy, Balázs/0000-0002-5772-3766; Tigyi, Gabor/0000-0001-5371-171X; Benyó, Zoltán/0000-0001-6015-0359}
}

@article{MTMT:35172465,
	title = {Artificial intelligence methods available for cancer research},
	url = {https://m2.mtmt.hu/api/publication/35172465},
	author = {Murmu, Ankita and Győrffy, Balázs},
	doi = {10.1007/s11684-024-1085-3},
	journal-iso = {FRONT MEDIC},
	journal = {FRONTIERS OF MEDICINE},
	volume = {In press},
	unique-id = {35172465},
	issn = {2095-0217},
	abstract = {Cancer is a heterogeneous and multifaceted disease with a significant global footprint. Despite substantial technological advancements for battling cancer, early diagnosis and selection of effective treatment remains a challenge. With the convenience of large-scale datasets including multiple levels of data, new bioinformatic tools are needed to transform this wealth of information into clinically useful decision-support tools. In this field, artificial intelligence (AI) technologies with their highly diverse applications are rapidly gaining ground. Machine learning methods, such as Bayesian networks, support vector machines, decision trees, random forests, gradient boosting, and K-nearest neighbors, including neural network models like deep learning, have proven valuable in predictive, prognostic, and diagnostic studies. Researchers have recently employed large language models to tackle new dimensions of problems. However, leveraging the opportunity to utilize AI in clinical settings will require surpassing significant obstacles-a major issue is the lack of use of the available reporting guidelines obstructing the reproducibility of published studies. In this review, we discuss the applications of AI methods and explore their benefits and limitations. We summarize the available guidelines for AI in healthcare and highlight the potential role and impact of AI models on future directions in cancer research.},
	keywords = {BREAST-CANCER; PREDICTION; machine learning; Oncology; guideline; NEURAL-NETWORKS; Decision tree; Computer-aided detection; artificial neural network; natural language processing; survival prediction; Electronic Health Records; Deep learning; FEATURE-SELECTION; level classification; Radiomics analysis},
	year = {2024},
	eissn = {2095-0225},
	orcid-numbers = {Murmu, Ankita/0000-0002-0198-5214; Győrffy, Balázs/0000-0002-5772-3766}
}

@article{MTMT:35172447,
	title = {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)},
	url = {https://m2.mtmt.hu/api/publication/35172447},
	author = {Menyhart, Otilia and Fekete, János Tibor and Győrffy, Balázs},
	doi = {10.3390/ijms25158441},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {25},
	unique-id = {35172447},
	issn = {1661-6596},
	abstract = {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.},
	keywords = {[Meta-analysis]},
	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}
}

@article{MTMT:35162223,
	title = {Adherence to the Mediterranean diet and its protective effects against colorectal cancer: a meta-analysis of 26 studies with 2,217,404 participants},
	url = {https://m2.mtmt.hu/api/publication/35162223},
	author = {Ungvári, Zoltán István and Fekete, Mónika and Fekete, János Tibor and Grosso, Giuseppe and Ungvári, Anna Sára and Győrffy, Balázs},
	doi = {10.1007/s11357-024-01296-9},
	journal-iso = {GEROSCIENCE},
	journal = {GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE)},
	volume = {In press},
	unique-id = {35162223},
	issn = {2509-2715},
	abstract = {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.},
	keywords = {[Meta-analysis]},
	year = {2024},
	eissn = {2509-2723},
	orcid-numbers = {Ungvári, Zoltán István/0000-0002-6035-6039; Fekete, Mónika/0000-0001-8632-2120; Fekete, János Tibor/0000-0002-6672-6563; Győrffy, Balázs/0000-0002-5772-3766}
}

@article{MTMT:35151889,
	title = {STAT3 in acute myeloid leukemia facilitates natural killer cell-mediated surveillance},
	url = {https://m2.mtmt.hu/api/publication/35151889},
	author = {Witalisz-Siepracka, A. and Denk, C.-M. and Zdársky, B. and Hofmann, L. and Edtmayer, S. and Harm, T. and Weiss, S. and Heindl, K. and Hessenberger, M. and Summer, S. and Dutta, S. and Casanova, E. and Obermair, G.J. and Győrffy, Balázs and Putz, E.M. and Sill, H. and Stoiber, D.},
	doi = {10.3389/fimmu.2024.1374068},
	journal-iso = {FRONT IMMUNOL},
	journal = {FRONTIERS IN IMMUNOLOGY},
	volume = {15},
	unique-id = {35151889},
	issn = {1664-3224},
	year = {2024},
	eissn = {1664-3224},
	orcid-numbers = {Győrffy, Balázs/0000-0002-5772-3766}
}