Prediction of Chemotherapeutic Efficacy in Non–Small Cell Lung Cancer by Serum Metabolomic Profiling

Abstract

In clinical practice, there are currently no validated biomarkers that can, prior to treatment, reliably indicate the intrinsically sensitive or resistant features of a non-squamous NSCLC patient to pemetrexed plus platinum doublet chemotherapy. In this study, we investigated the metabolic characteristics of a large cohort of pre-chemotherapeutic serum samples (354 cases) and found tight associations between small metabolite subsets and the responses of patients to this cytotoxic drug combination. We developed an effective discriminant model employing a seven-metabolite panel (Hypotaurine, Uridine, Dodecanoylcarnitine, Choline, Dimethylglycine, Niacinamide, L-palmitoylcarnitine) that can predict the efficacy of this chemotherapeutic regimens, prior to treatment, with a sensitivity of 90.8% and specificity of 79.5%. We also identified three one-carbon metabolism-involved metabolites including choline, betaine and DMG that are potentially associated with drug resistance to pemetrexed. This serum-based biomarker study can be easily applied in clinical practice and personalize treatment decisions. Conclusion:This study developed an effective and convenient discriminant model that can accurately predict the efficacy and survival outcomes of pemetrexed plus platinum doublet chemotherapy prior to treatment delivery.

Circulating Tumor Cell and Metabolites as Novel Biomarkers for Early-stage Lung Cancer Diagnosis

“…Yang et al found 25 different lipid metabolites, including PE, between malignant pleural effusion (MPE) and benign pleural effusion (NPE), indicating that lipid metabolites may be used to partition MBE and BPE [44]. In our study, PE One Study showed that L-palmitoylcarnitine is signi cantly reduced in advanced lung cancer patients [46]. In another study, the level of palmitoylcarnitine was lower in the hepatocellular carcinoma group than in the cancer-free control group, and blood acylcarnitine levels may be in uenced by hepatic fatty acid metabolism, in other words, decreased acylcarnitine levels may re ect the decreased production of acyl groups in the liver or other tissues.…”

Combined Metabolomic Analysis of Plasma and Tissue Reveals a Prognostic Risk Score System and Metabolic Dysregulation in Esophageal Squamous Cell Carcinoma

“…Circulating-metabolite-based prognostic models have previously been shown to have its promising clinical applications in several cancers, such as glioblastoma (34), non-small cell lung cancer (35), and esophageal adenocarcinoma (24). However, the previous metabolomic studies of ESCC solely focused on the diagnostic value of the metabolites and rarely assessed their prognostic significance.…”

Modeling of Nanotherapy Response as a Function of the Tumor Microenvironment: Focus on Liver Metastasis

“…For example, metabolomics provides insight into outcomes of transcription changes, which reflect differential functionality of specific metabolites influencing the tumor response. Attempts to predict therapy response based on metabolomics analysis only (Tian et al, 2018) or gene expression (Geeleher and Cox, 2014) yield results typically relying on statistical analyses that do not necessarily represent any particular tumor (Peng et al, 2018;Mucaki et al, 2019). Ideally, a mathematical-based framework would be capable of recreating particular patients' tumors for in silico prediction of behavior in time and space prior to treatment, incorporating omics data for patient customization, and thus move toward the goal of predictive personalized treatment.…”