Analysis of Kynurenine/Tryptophan ratio and expression of IDO1 and 2 mRNA in tumour tissue of cervical cancer patients

Clin Biochem. 2016 Aug;49(12):919-24. doi: 10.1016/j.clinbiochem.2016.04.008. Epub 2016 Apr 20.

Abstract

Objectives: Indoleamine 2,3-Dioxygenase (IDO) catalyses the degradation of the essential amino acid tryptophan leading to the production of immunosuppressive Kynurenine. In the present study, we developed a modified method for measurement of Kynurenine/tryptophan (K/T) ratio in the cervical tissue using HPLC and investigated its relationship with the expression of IDO1 and 2 genes in the cervical tumour milieu.

Design and methods: Cervical cancer punch biopsy samples of 27 women who presented at the Cancer Institute (WIA) were used for detection of K/T ratio by HPLC as well as expression of IDO1 and 2 at the mRNA level by Realtime PCR after obtaining Institutional ethical committee approval.

Results: The K/T ratio was elevated significantly in cancer cervix samples compared to normal cervix (p<0.05). IDO1 mRNA levels were up-regulated whereas IDO2 mRNA levels were down-regulated in cancer cervix compared to the normal cervix. A positive correlation was observed between IDO1 and K/T (p<0.05) indicating that IDO1 was responsible for the increase in K/T ratio.

Conclusion: Our preliminary data indicates that the K/T ratio at the tissue level may be investigated reliably using HPLC, as an indirect measure of IDO1 gene expression and activity.

Keywords: Cervical cancer; HPLC; IDO; Kynurenine; Tryptophan.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Case-Control Studies
  • Chromatography, High Pressure Liquid
  • Female
  • Follow-Up Studies
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics*
  • Kynurenine / metabolism*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / genetics*
  • Real-Time Polymerase Chain Reaction
  • Survival Rate
  • Tryptophan / metabolism*
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • IDO1 protein, human
  • IDO2 protein, human
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • RNA, Messenger
  • Kynurenine
  • Tryptophan