Urinary metabonomic study of lung cancer by a fully automatic hyphenated hydrophilic interaction/RPLC‐MS system

Abstract

Lung cancer is one of the most common and lethal cancers in the world. In this study, a home-devised hydrophilic interaction chromatography/RPLC-MS (HILIC/RPLC-MS) system was developed to study the urinary metabonomics of lung cancer patients. This system combined the orthogonal selectivity of HILIC and RPLC and could chromatographically reveal more comprehensive information of the urinary metabolites. Within a total analysis time of 50 min, we detected 577 polar metabolite ions on the first HILIC column and 261 apolar ones on the second RPLC column. In addition, an orthogonal signal correction partial least-squares discriminant analysis model was constructed to characterize differences between health and lung cancer cases. Eleven potential biomarkers, ten from HILIC column and one from the second RP column, were identified and all of these biomarkers were found upregulated in lung cancer patients. Overall, the results indicated that the developed HILIC/RPLC-MS system is a promising tool for metabonomic studies in revealing more information of highly complex samples.

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

“…Thus, we speculated that tyrosine metabolism is also disturbed in lung cancer patients, resulting in PHPLA accumulation. The second potential biomarker we had speculated out was proline betaine (ion with t R -m/z 6.80-144.097), which also had been found in the urinary metabonomic study of lung cancer [42]. We found that the change trend of proline betaine in our plasma metabonomic study was same as the urinary metabonomic study [42].…”

“…When comparing with the markers which had been found in the urinary metabonomic study [42], we found many different marker ions despite several same potential markers in the plasma. It meant that new biomarkers could be found by the plasma metabonomic study.…”

“…During the preparation of this manuscript, a report was published describing urinary metabonomic study of lung cancer by 2D-HILIC-RPLC/MS system [42]. However, metabonomic studies of lung cancer or the effect of radiotherapy on cancer patients, especially the studies of highly polar metabolites in cancer patients' plasma, were still limited.…”

Metabolomics for tumor marker discovery and identification based on chromatography–mass spectrometry

“…Review MS-based metabolomic platforms are increasingly applied to the screening of tumor markers and have been used in recent years for colorectal cancer [39][40][41][42][43][44][45][46], lung cancer [47][48][49][50][51][52][53], papillary thyroid carcinoma [54], oral cancer [55,56] and pancreatic cancer [57]. Here, due to space limitations, the authors review the development of metabolomics in the discovery of tumor markers only for specific malignancies with high incidence, including primary liver cancer, gynecologic cancer and genitourinary cancer.…”

Biomarker discovery of liver diseases using mass spectrometry-based metabolomics.

“…While most of the LC-MS analyses use reverse phase liquid chromatography (RP-LC) to separate metabolites before MS analysis [48], hydrophobic interaction liquid chromatography (HILIC) has emerged as another choice of separation platform for LC-MS based metabolomics [49]. HILIC is similar to normal phase LC, in that the stationary phase is polar; however, in contrast to normal phase LC, the mobile phase in HILIC uses water miscible solvents, such as acetonitrile or methanol, and also contains a substantial amount of water.…”