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Article

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

1
Section of Anatomic Pathology and Histology, Department of Medicine and Surgery, University of Perugia, 06129 Perugia, Italy
2
Section of Pharmacology, Department of Medicine and Surgery, University of Perugia, 06129 Perugia, Italy
3
Section of Thoracic Surgery, Department of Medicine and Surgery, University of Perugia, 06129 Perugia, Italy
4
Medical Oncology Division, Santa Maria della Misericordia Hospital, 06132 Perugia, Italy
5
Division of Medical Oncology, Ospedali Riuniti Padova Sud, 35043 Monselice, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Stefano Indraccolo
Int. J. Mol. Sci. 2021, 22(9), 4403; https://doi.org/10.3390/ijms22094403
Received: 16 March 2021 / Revised: 14 April 2021 / Accepted: 20 April 2021 / Published: 22 April 2021
(This article belongs to the Special Issue Decoding the Complex Crossroad of Tryptophan Metabolic Pathways)
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. View Full-Text
Keywords: kynurenine/tryptophan (Kyn/Trp) ratio; indoleamine-2,3-dioxygenase 1 (IDO1); non-small cell lung cancer (NSCLC); immunohistochemical biomarkers; serum biomarkers kynurenine/tryptophan (Kyn/Trp) ratio; indoleamine-2,3-dioxygenase 1 (IDO1); non-small cell lung cancer (NSCLC); immunohistochemical biomarkers; serum biomarkers
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MDPI and ACS Style

Mandarano, M.; Orecchini, E.; Bellezza, G.; Vannucci, J.; Ludovini, V.; Baglivo, S.; Tofanetti, F.R.; Chiari, R.; Loreti, E.; Puma, F.; Sidoni, A.; Belladonna, M.L. Kynurenine/Tryptophan Ratio as a Potential Blood-Based Biomarker in Non-Small Cell Lung Cancer. Int. J. Mol. Sci. 2021, 22, 4403. https://doi.org/10.3390/ijms22094403

AMA Style

Mandarano M, Orecchini E, Bellezza G, Vannucci J, Ludovini V, Baglivo S, Tofanetti FR, Chiari R, Loreti E, Puma F, Sidoni A, Belladonna ML. Kynurenine/Tryptophan Ratio as a Potential Blood-Based Biomarker in Non-Small Cell Lung Cancer. International Journal of Molecular Sciences. 2021; 22(9):4403. https://doi.org/10.3390/ijms22094403

Chicago/Turabian Style

Mandarano, Martina, Elena Orecchini, Guido Bellezza, Jacopo Vannucci, Vienna Ludovini, Sara Baglivo, Francesca R. Tofanetti, Rita Chiari, Elisabetta Loreti, Francesco Puma, Angelo Sidoni, and Maria L. Belladonna 2021. "Kynurenine/Tryptophan Ratio as a Potential Blood-Based Biomarker in Non-Small Cell Lung Cancer" International Journal of Molecular Sciences 22, no. 9: 4403. https://doi.org/10.3390/ijms22094403

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