Cheng Jing, Jin Hai, Hou Xiaobei, Lv Jie, Gao Xianfu, Zheng Guangyong
Department of Medical Instrument, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Road, Shanghai 201318, China.
Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.
Biochem Biophys Res Commun. 2017 May 6;486(3):781-787. doi: 10.1016/j.bbrc.2017.03.120. Epub 2017 Mar 23.
Esophageal squamous cell carcinoma (ESCC) is one of the most frequent malignancies worldwide. Lymph node metastasis is the leading cause of death in ESCC patients. To identify early diagnostic and prognostic biomarkers of ESCC and elucidate underlying pathogenesis of the disease, a targeted metabolomics strategy based on liquid chromatography combined with tandem mass spectrometry was applied to explore tryptophan metabolism between ESCC patients, metastatic ESCC patients (mESCC), and healthy controls. Statistical analysis on metabolite expression abundance and compound concentration ratio was conducted to discriminate patients from healthy controls. The concentration ratio of kynurenine, 5-hydroxytryptophan, 5-hydroxyindole-3-acetic acid, 5-hydroxytryptamine to their precursor tryptophan were identified as potential biomarkers, presenting high diagnostic capacity for distinguishing ESCC and mESCC patients from healthy controls. Moreover, a prognostic prediction model was also built on these ratios to distinguish metastasis patients from non-metastasis patients successfully. The high performance of ESCC prediction models suggest that concentration ratios of compounds may be used as biomarkers for early diagnosis and prognosis of the disease. In addition, concentration ratios of compounds show a progressively increased trend from non-metastasis to metastasis patients compared with healthy controls, which is in accordance with process of malignant transformation of ESCC. This interested finding suggests that disturbed tryptophan metabolism is correlated to progression and metastasis of ESCC since concentration ratios of compounds reflect activity of enzymes involved in tryptophan metabolism. This study reveals the impact of tryptophan metabolism to tumorigenesis and metastasis of ESCC, which help biologists investigate mechanism of the disease.
食管鳞状细胞癌（ESCC）是全球最常见的恶性肿瘤之一。淋巴结转移是ESCC患者死亡的主要原因。为了识别ESCC的早期诊断和预后生物标志物，并阐明该疾病的潜在发病机制，采用了基于液相色谱结合串联质谱的靶向代谢组学策略，以探索ESCC患者、转移性ESCC患者（mESCC）和健康对照者之间的色氨酸代谢情况。对代谢物表达丰度和化合物浓度比进行统计分析，以区分患者和健康对照者。犬尿氨酸、5-羟色氨酸、5-羟吲哚-3-乙酸、5-羟色胺与其前体色氨酸的浓度比被确定为潜在的生物标志物，对区分ESCC和mESCC患者与健康对照者具有较高的诊断能力。此外，还基于这些比率建立了一个预后预测模型，以成功区分转移患者和非转移患者。ESCC预测模型的高性能表明，化合物的浓度比可用作该疾病早期诊断和预后的生物标志物。此外，与健康对照者相比，化合物的浓度比在从非转移患者到转移患者中呈逐渐增加的趋势，这与ESCC的恶性转化过程一致。这一有趣的发现表明，色氨酸代谢紊乱与ESCC的进展和转移相关，因为化合物的浓度比反映了色氨酸代谢中涉及的酶的活性。本研究揭示了色氨酸代谢对ESCC肿瘤发生和转移的影响，有助于生物学家研究该疾病的机制。
