title: Perioperative dynamics and significance of amino acid profiles in patients with cancer.
abstract: BACKGROUND
  Metabolome analysis including amino acid profile is under investigation as an approach in cancer screening. The present study aims to analyze plasma free amino acid (PFAA) profiles in cancer patients and investigate their potential as biomarkers of malignancy.
  
  
  METHODS
  Plasma samples from 56 gastric cancer patients, 28 breast cancer patients, 33 thyroid cancer patients, and 137 age-matched healthy controls were collected in the study. PFAA levels were measured and their perioperative alterations were analyzed. Biological effects of ten cancer-related amino acids were further validated in gastric and breast cancer cells.
  
  
  RESULTS
  We found that PFAA profiles of cancer patients differed significantly from those of healthy controls. Decreased concentrations of PFAAs were associated with lymph node metastases in gastric cancer. Levels of PFAAs such as aspartate and alanine increased after tumor resection. PFAA levels correlated with clinical tumor markers in gastric cancer patients and pathological immunohistochemistry markers in breast cancer patients. Specifically, alanine, arginine, aspartate and cysteine had proliferative effects on breast cancer cells. Proliferation of gastric cancer cells was promoted by cysteine, but inhibited by alanine and glutamic acid. Furthermore, alanine treatment decreased total and stable fraction of gastric cancer cells, and alanine and glutamic acid induced apoptosis of gastric cancer cells.
  
  
  CONCLUSIONS
  PFAA patterns in cancer patients are altered perioperatively. Tumor-related amino acids identified by dynamic study of PFAA patterns may have the potential to be developed as novel biomarkers for diagnosis and prognosis of cancer patients.
authors.affiliation: Department of Surgical Oncology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. ivorygoo@126.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Thoracic Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. zjutxchen@163.com.
authors.forename: Tianxiang
authors.initials: T
authors.lastname: Chen
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. vir2lib@gmail.com.
authors.forename: Suzhen
authors.initials: S
authors.lastname: Fu
authors.affiliation: Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, USA. xsun10@jhmi.edu.
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.affiliation: Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, China. alick333@126.com.
authors.forename: Lingyan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, China. 251328610@qq.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. 13857196421@163.com.
authors.forename: Yingfeng
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. dsm00012380@126.com.
authors.forename: Songming
authors.initials: S
authors.lastname: Ding
authors.affiliation: Department of Oncology, The Second Hospital of Shaoxing, Shaoxing, China. recardos@163.com.
authors.forename: Guodong
authors.initials: G
authors.lastname: Ruan
authors.affiliation: Department of Surgical Oncology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. lsteng@zju.edu.cn.
authors.forename: Lisong
authors.initials: L
authors.lastname: Teng
authors.affiliation: Department of Surgical Oncology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. wangm198@hotmail.com.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
mesh_terms: D000409:Alanine / Q000494:pharmacology; D000596:Amino Acids / Q000097:blood*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000097:blood; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D018698:Glutamic Acid / Q000494:pharmacology; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000145:classification / Q000473:pathology / Q000601:surgery*; D019990:Perioperative Care
chemical_list: D000596:Amino Acids; D014408:Biomarkers, Tumor; D018698:Glutamic Acid; D000409:Alanine