Unveiling the altered metabolic pathways induced by nivolumab in non-small cell lung cancer via GC-MS metabolomics approach coupled with multivariate analysis

Manal E Alosaimi; Badriyah S Alotaibi; Maram H Abduljabbar; Reem M Alnemari; Atiah H Almalki; Ahmed Serag

doi:10.1016/j.jchromb.2024.124144

Unveiling the altered metabolic pathways induced by nivolumab in non-small cell lung cancer via GC-MS metabolomics approach coupled with multivariate analysis

J Chromatogr B Analyt Technol Biomed Life Sci. 2024 Apr 30:1240:124144. doi: 10.1016/j.jchromb.2024.124144. Online ahead of print.

Authors

Manal E Alosaimi¹, Badriyah S Alotaibi², Maram H Abduljabbar³, Reem M Alnemari⁴, Atiah H Almalki⁵, Ahmed Serag⁶

Affiliations

¹ Department of Basic Sciences, College of Medicine, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
² Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
³ Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
⁴ Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
⁵ Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia; Addiction and Neuroscience Research Unit, Health Science Campus, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
⁶ Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Nasr City 11751, Cairo, Egypt. Electronic address: Ahmedserag777@hotmail.com.

PMID: 38703714
DOI: 10.1016/j.jchromb.2024.124144

Abstract

This research investigates the effects of the immunotherapeutic agent nivolumab on the metabolism of lung cancer cells (NCI-H1975) using GC-MS metabolomic profiling. Multivariate analysis such as unsupervised PCA and supervised OPLS-DA along with univariate analysis and pathway analysis were employed to explore the metabolomic data and identify altered metabolic pathways induced by nivolumab treatment. The study revealed distinct metabolic alterations in cancer cells, linked to proliferative and survival advantages, such as enhanced glycolysis, increased glutaminolysis, and modified amino acid metabolism. Key findings indicate elevated levels of glycolysis-related metabolites (glycine, alanine, pyruvate, and lactate) and TCA cycle intermediates (succinate, fumarate, malate) in cancer cells, with a significant decrease following nivolumab treatment. Additionally, lower levels of aspartic acid and citrate in cancer cells imply altered nucleotide synthesis and fatty acid production essential for tumor growth. Treatment with nivolumab also reduced oleic acid levels, indicative of its effect on disrupted lipid metabolism. Our research shows nivolumab's potential to modify metabolic pathways involved in lung cancer progression, suggesting its dual role in cancer therapy: as an immune response modulator and a metabolic pathway disruptor.

Keywords: GC–MS; Immune Checkpoint Inhibitors; Lung Cancer Treatment; Metabolic Reprogramming; Metabolomics; Nivolumab.