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


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.


CONCLUSIONS
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.
Department of Molecular Oncology, Cancer Institute (WIA), India.
Jayakumar
J
Hascitha
Department of Molecular Oncology, Cancer Institute (WIA), India.
Ramanathan
R
Priya
Department of Molecular Oncology, Cancer Institute (WIA), India.
Subramani
S
Jayavelu
Department of Molecular Oncology, Cancer Institute (WIA), India.
Hemavathi
H
Dhandapani
Department of Radiation Oncology, Cancer Institute (WIA), India.
Ganeshrajah
G
Selvaluxmy
Department of Onco-pathology, Cancer Institute (WIA), India.
Shirley
S
Sunder Singh
Department of Molecular Oncology, Cancer Institute (WIA), India. Electronic address: drtrajkumar@gmail.com.
Thangarajan
T
Rajkumar
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics*; D007737:Kynurenine / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D015996:Survival Rate; D014364:Tryptophan / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; C576710:IDO1 protein, human; C576711:IDO2 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012333:RNA, Messenger; D007737:Kynurenine; D014364:Tryptophan
Cervical cancer; HPLC; IDO; Kynurenine; Tryptophan