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Poster display - Cocktail

1282 - Association between altered expression of key enzymes involved in kynurenine pathway with clinical outcome in patients with different grades of astrocytoma

Date

24 Nov 2018

Session

Poster display - Cocktail

Presenters

Dheeraj Mohania

Citation

Annals of Oncology (2018) 29 (suppl_9): ix21-ix22. 10.1093/annonc/mdy429

Authors

D. Mohania1, P. Kumar2, D. Goyal1, R. Acharya3, S.K. Kalra3, S. Jain4, S. Bhalla4, S. Misra5, A. Kumar5

Author affiliations

  • 1 Dr. R. P. Centre, All India Institute of Medical Sciences, 110029 - New Delhi/IN
  • 2 Urology, University of Alabama, 720 - AL /US
  • 3 Neurosurgery, Sir Ganga Ram Hospital, 110060 - New Delhi/IN
  • 4 Pathology, Sir Ganga Ram Hospital, 110060 - New Delhi/IN
  • 5 Neurology, All India Institute of Medical Sciences, 110029 - New Delhi/IN
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Resources

Abstract 1282

Background

The kynurenine pathway (KP) is responsible for majority of the TRP metabolism in the central nervous system, and in glioma patients, this pathway becomes highly deregulated. Therefore, we aimed at comprehensive expression analysis of all KP enzymes in different grades of astrocytoma patients and their correlation with clinical outcome.

Methods

Twenty nine astrocytoma patients and healthy controls (n = 20) were enrolled in this study. Patients were segregated into pilocytic (PA), diffuse (DA), anaplastic (AA) and glioblastoma multiforme (GBM). Transcriptional analysis of all KP key enzymes was evaluated by Real-time PCR. Ki-67 proliferation index was evaluated by immunohistochemistry.

Results

We report the first comprehensive expression analysis of all KP enzymes in patients with different grades of astrocytoma. Our data revealed a significant correlation between tumor volume and relative mRNA expression levels of IDO-2 (n = 7, Spearman’s rho= 0.8571, P = 0.0137) and AFMID (n = 20, Spearman’s rho= 0.05805, P = 0.0073). One-way ANOVA analysis showed significantly higher mRNA expression levels of KMO in AA patients (P < 0.009). There was also a significant correlation of relative mRNA expression levels of various KP enzymes in PA, DA, AA and GBM patients in comparison to controls (P < 0.05). The mean of proliferation index of Ki-67 was significantly higher (P < 0.001) in GBM as compared to PA, DA and AA patients. ROC analysis suggested Ki-67 is substantially good determinant for predicting death in different grades of astrocytoma (AUC=0.812, 95% CI 0.64 to 0.97). Youden index showed Ki-67 cut-off (4.75) has sensitivity (0.88) and specificity (0.69) for predicting death. Logistic regression analysis showed significant association of Ki-67 with mortality (OR = 15.75, 95% CI 2.3 to 104.55, P = 0.004). Kaplan-Meier survival analysis showed significant less survival in patients with higher Ki-67 proliferative index.

Conclusions

This study provides an important insight of various kynurenine pathway (KP) enzymes and proliferation index of Ki-67 which correlates with clinical outcome and demonstrates the clinical relevance of KP enzymes in patients with different grades of astrocytoma.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

All India Institute of Medical Sciences (AIIMS), New Delhi, India.

Funding

Department of Science and Technology (DST), Government of India, New Delhi.

Disclosure

All authors have declared no conflicts of interest.

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