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在结直肠癌和泛癌分析中探索谷氨酸草酰乙酸转氨酶1作为生物标志物和治疗靶点的多方面作用。

Exploring the multifaceted roles of glutamate oxaloacetate transaminase 1 as a biomarker and therapeutic target in colorectal cancer and pan-cancer analyses.

作者信息

Wang Xi, Pi Longquan, Chen Yuning, Tan Jiangyu, Wang Yingying, Xia Kaiyan, Zhou Xianchun

机构信息

Department of Oncology, Yanbian University Hospital, Yanji, Jilin, China.

Department of Dermatology, Yanbian University Hospital, Yanji, Jilin, China.

出版信息

Discov Oncol. 2025 Aug 23;16(1):1600. doi: 10.1007/s12672-025-03461-8.

Abstract

Colorectal cancer (CRC) is a global health issue requiring novel diagnostic and therapeutic approaches to improve patient outcomes. Glutamate oxaloacetate transaminase 1 (GOT1) plays a crucial role in metabolism and is associated with various cancers. However, its expression and potential as a diagnostic marker in CRC have not been thoroughly investigated. We analysed The Cancer Genome Atlas data on GOT1 normalised to transcripts per million. We used tools such as Gene Expression Profiling Interactive Analysis 2, logistic regression, receiver operating characteristic analysis, Sieber algorithm for immune detection, immune checkpoint gene correlation, cBioPortal analysis, and genomic sensitivities of cancers from the Genomics of Drug Sensitivity in Cancer and Cancer Therapeutics Response Portal to evaluate the association of GOT1 with CRC. GOT1 expression significantly varied across cancer types, showing high diagnostic value in colon adenocarcinoma and rectal adenocarcinoma. Moreover, it correlated with immune cells, such as CD8 T and plasma cells, and immune checkpoint genes LGALS9 and TNFRSF4. Tumour genetic variations differed in mutation burden, copy number alterations, and microsatellite instability. Drug sensitivities, including those of navitoclax and CCT036477, showed an association with GOT1 expression. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses suggested the involvement of GOT in cellular metabolism. Our comprehensive analysis revealed a critical role of GOT1 in CRC, confirming its role as a diagnostic and therapeutic target. Nonetheless, its role in tumorigenesis warrants further investigation.

摘要

结直肠癌(CRC)是一个全球性的健康问题,需要新的诊断和治疗方法来改善患者的预后。谷氨酸草酰乙酸转氨酶1(GOT1)在代谢中起关键作用,并与多种癌症相关。然而,其在结直肠癌中的表达及其作为诊断标志物的潜力尚未得到充分研究。我们分析了来自癌症基因组图谱中以每百万转录本标准化的GOT1数据。我们使用了诸如基因表达谱交互式分析2、逻辑回归、受试者工作特征分析、用于免疫检测的西伯算法、免疫检查点基因相关性分析、cBioPortal分析以及来自癌症药物敏感性基因组学和癌症治疗反应门户的癌症基因组敏感性等工具,以评估GOT1与结直肠癌的关联。GOT1的表达在不同癌症类型中差异显著,在结肠腺癌和直肠腺癌中显示出较高的诊断价值。此外,它与免疫细胞,如CD8 T细胞和浆细胞,以及免疫检查点基因LGALS9和TNFRSF4相关。肿瘤基因变异在突变负担、拷贝数改变和微卫星不稳定性方面存在差异。包括维托卡克斯和CCT036477在内的药物敏感性与GOT1表达相关。基因本体论和京都基因与基因组百科全书分析表明GOT参与细胞代谢。我们的综合分析揭示了GOT1在结直肠癌中的关键作用,证实了其作为诊断和治疗靶点的作用。尽管如此,其在肿瘤发生中的作用仍有待进一步研究。

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