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Higher MAT2A mRNA associates with worse survival, while MAT2A protein is detected in cytoplasm and nucleus, with sex-specific prognostic patterns. 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Translocation of Methionine  \nAdenosyl Transferase MAT2A and Its Prognostic Relevance for Liver Hepatocellular Carcinoma. Int. J. Mol. Sci. 2023, 24, 9103. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms24109103](10.3390/ijms24109103)  \nAcademic Editor: Caterina Cinti  \nReceived: 15 March 2023  \nRevised: 12 May 2023  \nAccepted: 16 May 2023  \nPublished: 22 May 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 402, Taiwan; chu.peiyi@msa.hinet.net  \n2 School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan  \n3 Department of Pathology, Show Chwan Memorial Hospital, Changhua 500, Taiwan  \n4 National Institute of Cancer Research, National Health Research Institutes, Tainan 704, Taiwan  \n5 Department of General Surgery, Changhua Show Chwan Memorial Hospital, Changhua 500, Taiwan  \n6 Research Assistant Center, Show Chwan Memorial Hospital, Changhua 500, Taiwan  \n7 Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 402, Taiwan  \n8 Innovation and Development Center of Sustainable Agriculture (IDCSA), National Chung Hsing University, Taichung 402, Taiwan  \n9 Advanced Plant and Food Crop Biotechnology Center (APFCBC), National Chung Hsing University, Taichung 402, Taiwan  \n* Correspondence: [chiangisabel@nchu.edu.tw](chiangisabel@nchu.edu.tw); Tel.: +886-4-22853049 † These authors contributed equally to this work.  \nAbstract: Methionine adenosyl transferases (MATs) catalyze the synthesis of the biological methyl donor adenosylmethionine (SAM) . Dysregulation of MATs has been associated with carcinogenesisin humans. We previously found that downregulation of the MAT1A gene enriches the proteinassociated translation process and worsens liver hepatocellular carcinoma (LIHC) prognosis. We also discovered that subcellular localization of the MAT2A protein has independently prognostic relevance in breast cancer patients. The present study aimed to examined the clinical relevance of MAT2A translocation in human LIHC. Essential methionine cycle gene expressions in TCGALIHC datasets were analyzed using Gene Expression Profiling Interactive Analysis 2 (GEPIA2) . The protein expression pattern of MAT2A was determined in the tissue array of our own LIHC cohort (n = 261) using immuno-histochemistry, and the prognostic relevance of MAT2A protein's subcellular localization expression was examined using Kaplan–Meier survival curves. LIHC patients with higher MAT2A mRNA expression had a worse survival rate (p = 0.0083) . MAT2A protein immunoreactivity was observed in both cytoplasm and nucleus fractions in the tissue array. Tumor tissues had elevated MAT2A protein expression in both cytoplasm and nucleus compared to their adjacent normal tissues. A higher cytoplasmic to nuclear MAT2A protein expression ratio (C/N) was found in female LIHC patients compared to that of male patients (p = 0.047) . Kaplan–Meier survival curves showed that a lower MAT2A C/N correlated with poor overall survival in female LIHC patients (10-year survival rate: 29.2% vs. 68.8%, C/N 􀀔 1.0 vs. C/N > 1.0, log-rank p = 0.004) . Moreover, we found that specificity protein 1 (SP1) may have a potential interaction with nuclear MAT2A protein, using protein–protein interaction; this we found us","cbCaipaOIGmOJMHZ","https://ap.wps.com/l/cbCaipaOIGmOJMHZ","pdf",5636357,15,"English","# Abstract\n# Introduction","[{\"question\":\"What was the main objective of this study on LIHC?\",\"answer\":\"To examine the clinical relevance of MAT2A translocation in human liver hepatocellular carcinoma (LIHC), focusing on how MAT2A localization relates to patient prognosis.\"},{\"question\":\"Which methods were used to assess MAT2A expression and prognosis in LIHC?\",\"answer\":\"The study analyzed essential methionine cycle gene expressions in TCGA LIHC datasets using GEPIA2, measured MAT2A protein patterns in a tissue array via immunohistochemistry, and evaluated prognostic relevance using Kaplan–Meier survival curves.\"},{\"question\":\"How does MAT2A relate to survival outcomes in LIHC patients?\",\"answer\":\"Higher MAT2A mRNA expression corresponded to worse survival. In addition, a lower cytoplasmic-to-nuclear MAT2A (C/N) ratio was associated with poor overall survival in female LIHC patients.\"}]","Translocation of Methionine Adenosyl Transferase MAT2A and Its Prognostic Relevance for Liver Hepatocellular Carcinoma | PDF",1790243959,38]