Cheng Jing, Liu Qi, Jin Hai, Zeng Dongdong, Liao Yuehua, Zhao Yuxia, Gao Xianfu, Zheng Guangyong
Department of Medical instrument, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Road, Shanghai 201318, China.
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN 37212, USA.
Biochim Biophys Acta Mol Basis Dis. 2021 Jan 1;1867(1):165966. doi: 10.1016/j.bbadis.2020.165966. Epub 2020 Sep 12.
Esophageal Squamous Cell Carcinoma (ESCC) is an aggressive malignancy, leading to more than 250,000 deaths in China every year. However, the pathogenesis of ESCC remains unclear, which hinders the diagnosis and treatment of the disease in clinic.
To elucidate underlying mechanism and identify potential biomarkers, an integrative strategy of combining transcriptome and metabolome has been implemented to find potential causal genes and metabolites for ESCC.
At the transcriptional level, dysregulated genes in ESCC patients were identified and pathway enrichment analysis discovered tyrosine metabolic pathway as a promising target. Subsequently, up- and down-stream metabolites of tyrosine pathway were explored through targeted metabolome approach. Five metabolites, i.e. phenylalanine, 4-hydroxyphenyllactic acid, 3,4-dihydroxyphenylalanine, 3,4-dihydroxyphenylacetic acid and tyrosine were identified as diagnosis biomarkers for ESCC and metastatic ESCC patients. A biological model incorporating both transcriptional and metabolic dysregulation was also established to illustrate the potential mechanism of tumorigenesis and metastasis for ESCC.
Integrative transcriptomics and metabolomics analysis suggested that tyrosine pathway was essential for the tumorigenesis and metastasis of ESCC primarily through altering immune response and regulating tumor microenvironment. This research sheds light on the pathogenesis of ESCC and discovers potential biomarkers for the diagnosis of the disease.
食管鳞状细胞癌（ESCC）是一种侵袭性恶性肿瘤，在中国每年导致超过25万人死亡。然而，ESCC的发病机制仍不清楚，这阻碍了该疾病在临床上的诊断和治疗。
为了阐明潜在机制并识别潜在生物标志物，已实施了一种将转录组学和代谢组学相结合的综合策略，以寻找ESCC潜在的因果基因和代谢物。
在转录水平上，鉴定出ESCC患者中失调的基因，通路富集分析发现酪氨酸代谢通路是一个有前景的靶点。随后，通过靶向代谢组学方法探索了酪氨酸通路的上下游代谢物。五种代谢物，即苯丙氨酸、4-羟基苯乳酸、3,4-二羟基苯丙氨酸、3,4-二羟基苯乙酸和酪氨酸被鉴定为ESCC及转移性ESCC患者的诊断生物标志物。还建立了一个整合转录和代谢失调的生物学模型，以阐明ESCC肿瘤发生和转移的潜在机制。
转录组学和代谢组学的综合分析表明，酪氨酸通路主要通过改变免疫反应和调节肿瘤微环境对ESCC的肿瘤发生和转移至关重要。本研究揭示了ESCC的发病机制，并发现了该疾病诊断的潜在生物标志物。
