Metabonomic Study of Lung Cancer and the Effects of Radiotherapy on Lung Cancer Patients: Analysis of Highly Polar Metabolites by Ultraperformance HILIC Coupled with Q-TOF MS

Abstract

In this study, plasma samples were collected from 28 health volunteers and 66 lung cancer patients. Ultraperformance HILIC/Q-TOF MS-based metabonomic techniques were employed to compare the highly polar metabolites (HPMs) in the plasma of patients with lung cancer and those in the plasma of healthy volunteers. High separation efficiency and good repeatability of the HILIC/ Q-TOF MS method were observed. Partial least squares discriminant analysis (PLS-DA) of the data from both ESI? and ESI-mode revealed good classifications between the health volunteer and the lung cancer patients. This result showed that the HPMs from lung cancer patients and healthy controls were significantly different. The correct classification rate of models in both ion modes reached 100%, indicating that the metabonomics method established in this study could predict the plasma samples with high accuracy. Besides, we found 19 ions that show a significant difference in levels between lung cancer patients and healthy controls. Finally, we conducted a primary study of the effect of radiotherapy on HPMs in lung cancer patients. Clear differences among the HPMs of patients in different radiotherapy periods and significant changes in levels of the 19 ions after radiotherapy were noted. This demonstrated that radiotherapy influences the metabolism system of patients.

Analysis of human plasma metabolites across different liquid chromatography/mass spectrometry platforms: Cross‐platform transferable chemical signatures

“…[3,7,8] Plasma has been profiled for the discovery of biomarkers in cancers. A few examples include hepatocellular carcinoma, [9] pancreatic, [10] epithelial ovarian, [11] prostate, [12] and lung [13] cancers. In these types of experiments metabolites specific to the disease of interest are sought by comparison of results between control and case samples.…”

Review of Mass Spectrometry–Based Metabolomics in Cancer Research

“…The authors concluded that the demethylation process could be hampered by radiation, proposing a mechanistic explanation as to why combining radiotherapy with Temozolomide (an alkylating drug) works so efficiently (20). Cai et al monitored metabolic changes in plasma of lung cancer patients treated with radiation, but did not identify possible biomarkers that could distinguish treated from untreated individuals (46). Some studies investigated the effect of surgical intervention on the metabolome (47-51).…”

UPLC-based metabonomic applications for discovering biomarkers of diseases in clinical chemistry

“…This method was also applied to the effect of radiotherapy on highly polar metabolites. Nineteen metabolites were altered at different points during the course of radiotherapy [58]. Serum and plasma metabonomics were developed and tested in patients with small-cell lung cancer.…”