Observational Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Oct 24, 2021; 12(10): 947-959
Published online Oct 24, 2021. doi: 10.5306/wjco.v12.i10.947
Novel molecular panel for evaluating systemic inflammation and survival in therapy naïve glioma patients
Puneet Gandhi, Richa Shrivastava, Nitin Garg, Sandeep K Sorte
Puneet Gandhi, Richa Shrivastava, Department of Research, Bhopal Memorial Hospital and Research Centre, Bhopal 462038, Madhya Pradesh, India
Nitin Garg, Sandeep K Sorte, Department of Neurosurgery, Bhopal Memorial Hospital and Research Centre, Bhopal 462038, Madhya Pradesh, India
Author contributions: Gandhi P conceived the concept, study design, interpretation of data, initial draft, and final review; Shrivastava R performed the data acquisition, analysis, and initial draft; Garg N and Sorte SK performed the patient enrollment, and clinical data and its interpretation.
Supported by Major Project Sanctioned by the Madhya Pradesh Council of Science & Technology to Dr. Puneet Gandhi, No. 249.
Institutional review board statement: The study was approved by institutional ethics and review committee (IRB/21/Res/11). The funding agency had no role in the study design of this project.
Informed consent statement: All study participants and/or legally authorized representative, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All authors declare that they have no conflicts of interest, financial or any other.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Puneet Gandhi, MSc, PhD, Full Professor, Department of Research, Bhopal Memorial Hospital and Research Centre, Raisen Bypass, BMHRC Campus, Bhopal 462038, Madhya Pradesh, India. puneetgandhi67@yahoo.com
Received: April 30, 2021
Peer-review started: April 30, 2021
First decision: June 16, 2021
Revised: June 21, 2021
Accepted: August 20, 2021
Article in press: August 20, 2021
Published online: October 24, 2021
Abstract
BACKGROUND

Inflammation is crucial to tumor progression. A traumatic event at a specific site in the brain activates the signaling molecules, which triggers inflammation as the initial response within the tumor and its surroundings. The educated immune cells and secreted proteins then initiate the inflammatory cascade leading to persistent chronic inflammation. Therefore, estimation of the circulating inflammatory indicators kynurenine (KYN), interleukin-6 (IL-6), tissue-inhibitor of matrix-metalloproteinase-1 and human telomerase reverse transcriptase (hTERT) along with neutrophil-lymphocyte ratio (NLR) has prognostic value.

AIM

To assess the utility of chosen inflammatory marker panel in estimating systemic inflammation.

METHODS

The chosen markers were quantitatively evaluated in 90 naive, molecularly sub-typed plasma samples of glioma. A correlation between the markers and confounders was assessed to establish their prognostication power. Follow-up on the levels of the indicators was done 3-mo post-surgery. To establish the validity of circulating KYN, it was also screened qualitatively by dot-immune-assay and by immunofluorescence-immunohistochemistry in tumor tissues.

RESULTS

Median values of circulating KYN, IL-6, hTERT, tissue-inhibitor of matrix-metalloproteinase-1 and NLR in isocitrate-dehydrogenase-mutant/wildtype and within the astrocytic sub-groups were estimated, which differed from controls, reaching statistical significance (P < 0.0001). All markers negatively correlated with mortality (P < 0.0001). Applying combination-statistics, the panel of KYN, IL-6, hTERT and NLR achieved higher sensitivity and specificity (> 90%) than stand-alone markers, to define survival. The inflammatory panel could discriminate between WHO grades, and isocitrate-dehydrogenase-mutant/wildtype and define differential survival between astrocytic isocitrate-dehydrogenase-mutant/ wildtype. Therefore, its assessment for precise disease prognosis is indicated. Association of KYN with NLR, IL-6 and hTERT was significant. Cox-regression described KYN, IL-6, NLR, and hTERT as good prognostic markers, independent of confounders. Multivariate linear-regression analysis confirmed the association of KYN and hTERT with inflammation marker IL-6.There was a concomitant significant decrease in their levels in a 3-mo follow-up.

CONCLUSION

The first evidence-based study of circulating-KYN in molecularly defined gliomas, wherein the tissue expression was found to be concomitant with plasma levels. A non-invasive model for assessing indicators of chronic systemic inflammation is proposed.

Keywords: Circulating, Glioma, Inflammatory marker, Kynurenine, Non-invasive, Prognostic

Core Tip: The current study is the first-ever analysis of the circulatory levels of kynurenine, interleukin-6, tissue-inhibitor of matrix-metalloproteinase-1 and human telomerase reverse transcriptase along with neutrophillymphocyteratio in a sizeable cohort of molecularly classified glioma samples. The ability of this panel to differentiate survival in glioma subgroups has been assessed. Evaluation of this inflammatory panel of potential biomarkers using the minimally invasive blood sample, for prognostication and targeted personalized therapy in glioma, is suggested.