Disturbed tryptophan metabolism correlating to progression and metastasis of esophageal squamous cell carcinoma.
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.
Department of Medical Instrument, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Road, Shanghai 201318, China.
Jing
J
Cheng
Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.
Hai
H
Jin
Department of Medical Instrument, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Road, Shanghai 201318, China.
Xiaobei
X
Hou
Department of Medical Instrument, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Road, Shanghai 201318, China.
Jie
J
Lv
Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China. Electronic address: xfgao@sibs.ac.cn.
Xianfu
X
Gao
Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China. Electronic address: gyzheng@picb.ac.cn.
Guangyong
G
Zheng
D006916:5-Hydroxytryptophan / Q000097:blood; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D016022:Case-Control Studies; D018450:Disease Progression; D042241:Early Diagnosis; D004938:Esophageal Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000097:blood; D007737:Kynurenine / Q000097:blood; D008207:Lymphatic Metastasis; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D011379:Prognosis; D012701:Serotonin / Q000097:blood; D014364:Tryptophan / Q000097:blood*
D014408:Biomarkers, Tumor; D012701:Serotonin; D007737:Kynurenine; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan; D006916:5-Hydroxytryptophan
Esophageal squamous cell carcinoma; Liquid chromatography; Lymph node metastasis; Tandem mass spectrometry; Tryptophan metabolism