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Kynurenine/Tryptophan Ratio as a Potential Blood-Based Biomarker in Non-Small Cell Lung Cancer.

ABSTRACT: The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) degrade tryptophan (Trp) into kynurenine (Kyn) at the initial step of an enzymatic pathway affecting T cell proliferation. IDO1 is highly expressed in various cancer types and associated with poor prognosis. Nevertheless, the serum Kyn/Trp concentration ratio has been suggested as a marker of cancer-associated immune suppression. We measured Kyn and Trp in blood samples of a wide cohort of non-small-cell lung cancer (NSCLC) patients, before they underwent surgery, and analyzed possible correlations of the Kyn/Trp ratio with either IDO1 expression or clinical-pathological parameters. Low Kyn/Trp significantly correlated with low IDO1 expression and never-smoker patients; while high Kyn/Trp was significantly associated with older (≥68 years) patients, advanced tumor stage, and squamous cell carcinoma (Sqcc), rather than the adenocarcinoma (Adc) histotype. Moreover, high Kyn/Trp was associated, among the Adc group, with higher tumor stages (II and III), and, among the Sqcc group, with a high density of tumor-infiltrating lymphocytes. A trend correlating the high Kyn/Trp ratio with the probability of recurrences from NSCLC was also found. In conclusion, high serum Kyn/Trp ratio, associated with clinical and histopathological parameters, may serve as a serum biomarker to optimize risk stratification and therapy of NSCLC patients.

SUBMITTER: Mandarano M

PROVIDER: S-EPMC8122814 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Kynurenine/Tryptophan Ratio as a Potential Blood-Based Biomarker in Non-Small Cell Lung Cancer.

Mandarano Martina M Orecchini Elena E Bellezza Guido G Vannucci Jacopo J Ludovini Vienna V Baglivo Sara S Tofanetti Francesca Romana FR Chiari Rita R Loreti Elisabetta E Puma Francesco F Sidoni Angelo A Belladonna Maria Laura ML

International journal of molecular sciences 20210422 9

The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) degrade tryptophan (Trp) into kynurenine (Kyn) at the initial step of an enzymatic pathway affecting T cell proliferation. IDO1 is highly expressed in various cancer types and associated with poor prognosis. Nevertheless, the serum Kyn/Trp concentration ratio has been suggested as a marker of cancer-associated immune suppression. We measured Kyn and Trp in blood samples of a wide cohort of non-small-cell lung cancer (NSCLC) patients, before they un ...[more]

PMID: 33922388

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Project description:Chlamydiosis is the major infectious disease responsible for significant morbidity and mortality in free-living koalas. Recently, it was reported that 28.5% of koalas infected with chlamydiosis were presented with no overt clinical signs. Identification and quantification of changes in plasma biomarkers' fluctuations have the potential to enhance C. pecorum detection and facilitate the monitoring of therapeutic efficacy of antibiotics to treat this disease in koalas. Therefore, concentrations of the essential amino acid tryptophan, tryptophan's metabolite kynurenine, and the kynurenine:tryptophan ratio were quantified by high-performance liquid chromatography in the plasma of clinically normal koalas (n = 35), koalas identified with chlamydial disease (n = 35) and koalas that had other non-chlamydial co-morbidities (n = 10). Results showed that there was a significant difference between the clinically normal versus diseased, and clinically normal versus 'other' (both p < 0.001) in kynurenine plasma concentrations and kynurenine:tryptophan ratio; and also between the clinically normal and diseased in tryptophan plasma concentrations (p = 0.001). Proposed reference ranges of tryptophan, kynurenine, and kynurenine:tryptophan ratio in koalas are: 4.27-10.4 μg/mL, 0.34-1.23 μg/mL, and 0.05-0.22, respectively. Proposed optimal cut-off points to differentiate between clinically normal and diseased are: ≤ 4.75 μg/mL (tryptophan), ≥ 0.88 μg/mL (kynurenine), and ≥ 0.12 (kynurenine:tryptophan); and ≤ 7.67 μg/mL (tryptophan), ≥ 1.18 μg/mL (kynurenine), and ≥ 0.16 (kynurenine:tryptophan) to differentiate between released/recovered and euthanised of the diseased/'other' koalas. Significant differences in haematological and biochemical analytes were in the plasma globulins between the clinically normal and diseased koalas (p = 0.01), and in alkaline phosphatase between the clinically normal and 'other' koalas (p = 0.03). Although these potential biomarkers, especially tryptophan, may not be specific for detecting C. pecorum from the rest of the population, kynurenine and the kynurenine:tryptophan ratio may have a role in identifying unhealthy koalas from the clinically normal ones, irrespective of the underlying cause.

Project description:BackgroundDefining the presence of acute and chronic brain inflammation remains a challenge to clinicians due to the heterogeneity of clinical presentations and aetiologies. However, defining the presence of neuroinflammation, and monitoring the effects of therapy is important given its reversible and potentially damaging nature. We investigated the utility of CSF metabolites in the diagnosis of primary neuroinflammatory disorders such as encephalitis and explored the potential pathogenic role of inflammation in epilepsy.MethodsCerebrospinal fluid (CSF) collected from 341 paediatric patients (169 males, median age 5.8 years, range 0.1-17.1) were examined. The patients were separated into a primary inflammatory disorder group (n = 90) and epilepsy group (n = 80), who were compared with three control groups including neurogenetic and structural (n = 76), neurodevelopmental disorders, psychiatric and functional neurological disorders (n = 63), and headache (n = 32).FindingsThere were statistically significant increases of CSF neopterin, kynurenine, quinolinic acid and kynurenine/tryptophan ratio (KYN/TRP) in the inflammation group compared to all control groups (all p < 0.0003). As biomarkers, at thresholds with 95% specificity, CSF neopterin had the best sensitivity for defining neuroinflammation (82%, CI 73-89), then quinolinic acid (57%, CI 47-67), KYN/TRP ratio (47%, CI 36-56) and kynurenine (37%, CI 28-48). CSF pleocytosis had sensitivity of 53%, CI 42-64). The area under the receiver operating characteristic curve (ROC AUC) of CSF neopterin (94.4% CI 91.0-97.7%) was superior to that of CSF pleocytosis (84.9% CI 79.5-90.4%) (p = 0.005). CSF kynurenic acid/kynurenine ratio (KYNA/KYN) was statistically decreased in the epilepsy group compared to all control groups (all p ≤ 0.0003), which was evident in most epilepsy subgroups.InterpretationHere we show that CSF neopterin, kynurenine, quinolinic acid and KYN/TRP are useful diagnostic and monitoring biomarkers of neuroinflammation. These findings provide biological insights into the role of inflammatory metabolism in neurological disorders and provide diagnostic and therapeutic opportunities for improved management of neurological diseases.FundingFinancial support for the study was granted by Dale NHMRC Investigator grant APP1193648, University of Sydney, Petre Foundation, Cerebral Palsy Alliance and Department of Biochemistry at the Children's Hospital at Westmead. Prof Guillemin is funded by NHMRC Investigator grant APP 1176660 and Macquarie University.

Project description:Two emerging biomarkers of environmental enteric dysfunction (EED) include plasma citrulline (CIT), and the kynurenine (KYN): tryptophan (TRP)/ (KT) ratio. We sought to investigate the plasma concentration of CIT and KT ratio among the children having dehydrating diarrhea and examine associations between concentrations of CIT and KT ratio with concurrent factors. For this analysis, we used cross-sectional data from a total of 102, 6-36 months old male children who suffered from non-cholera acute watery diarrhea and had some dehydration admitted to an urban diarrheal hospital, in Bangladesh. CIT, TRP, and KYN concentrations were determined at enrollment from plasma samples using ELIZA. At enrollment, the mean plasma CIT concentration was 864.48 ± 388.55 µmol/L. The mean plasma kynurenine, tryptophan concentrations, and the KT ratio (× 1000) were 6.93 ± 3.08 µmol/L, 33.44 ± 16.39 µmol/L, and 12.12 ± 18.10, respectively. With increasing child age, KYN concentration decreased (coefficient: - 0.26; 95%CI: - 0.49, - 0.04; p = 0.021); with increasing lymphocyte count, CIT concentration decreased (coef.: - 0.01; 95% CI: - 0.02,0.001, p = 0.004); the wasted child had decreased KT ratio (coef.: - 0.6; 95% CI: - 1.18, - 0.02; p = 0.042) after adjusting for potential covariates. The CIT concentration was associated with blood neutrophils (coef.: 0.02; 95% CI: 0.01, 0.03; p < 0.001), lymphocytes (coef.: - 0.02; 95% CI: - 0.03, - 0.02; p < 0.001) and monocyte (coef.: 0.06; 95% CI: 0.01, 0.11; p = 0.021); KYN concentration was negatively associated with basophil (coef.: - 0.62; 95% CI: - 1.23, - 0.01; p = 0.048) after adjusting for age. In addition, total stool output (gm) increased (coef.: 793.84; 95% CI: 187.16, 1400.52; p = 0.011) and also increased duration of hospital stay (hour) (coef.: 22.89; 95% CI: 10.24, 35.54; p = 0.001) with increasing CIT concentration. The morphological changes associated with EED may increase the risk of enteric infection and diarrheal disease among children. Further research is critically needed to better understand the complex mechanisms by which EED biomarkers may impact susceptibility to dehydrating diarrhea in children.

Dataset Information

Kynurenine/Tryptophan Ratio as a Potential Blood-Based Biomarker in Non-Small Cell Lung Cancer.

Publications

Kynurenine/Tryptophan Ratio as a Potential Blood-Based Biomarker in Non-Small Cell Lung Cancer.

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