Background Colorectal adenoma (CA) is an important precancerous lesion and early screening target of colorectal cancer (CRC). Lipids with numerous physiological functions are proved to be involved in the development of CRC. However, there is no lipidomic study with large-scale serum samples on diagnostic biomarkers for CA. Methods The serum lipidomics of CA patients (n = 50) and normal control (NR) (n = 50) was performed by ultra high performance liquid chromatography-high resolution mass spectrometry with electrospray ionization (UHPLC-ESI-HRMS). Univariate and multivariate statistical analyses were utilized to screen the differential lipids between groups, and combining the constituent ratio analysis and diagnostic efficiency evaluation by receiver operating characteristic (ROC) curve disclosed the potential mechanism and biomarkers for CA. Results There were obvious differences in serum lipid profiles between CA and NR groups. Totally, 79 differential lipids were selected by criterion of P < 0.05 and fold change > 1.5 or < 0.67. Triacylglycerols (TAGs) and phosphatidylcholines (PCs) were the major differential lipids with ratio > 60%, indicating these two lipid metabolic pathways showed evident disequilibrium, which could contribute to CA formation. Of them, 12 differential lipids had good diagnostic ability as candidate biomarkers for CA (AUC ≥ 0.900) by ROC analysis. Conclusions To our knowledge, this is the first attempt to profile serum lipidomics and explore lipid biomarkers of CA to help early screening of CRC. 12 differential lipids are obtained to act as potential diagnostic markers of CA. PCs and fatty acids were the main dysregulated biomarkers for CA in serum.

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LC-MS-based untargeted metabolomics have been proven to be an extremely promising technique to discover biomarkers and explore the mechanisms underlying diseases, which, however, relies heavily on sample pretreatment for metabolite extraction. In the present study, a systematic and pragmatic evaluation of eight protocols employing conventional metabolites extraction strategies, protein precipitation (PPT), and liquid–liquid extraction (LLE), with and without proteinase K (PK) incubation, was performed simultaneously, using human plasma and a mixture of 39 endogenous metabolite standards. These protocols were as follows: (1) PPT with methanol, (2) PPT with acetonitrile, (3) PPT with 2-propanol, (4) two-step LLE of CH2Cl2–MeOH, followed by MeOH–H2O, (5) PK incubation combining two-step LLE of CH2Cl2–MeOH followed by MeOH–H2O, (6) two-step LLE of CHCl3–MeOH, followed by MeOH–H2O, (7) PK incubation combining two-step LLE of CHCl3–MeOH, followed by MeOH–H2O, (8) PK incubation combining MeOH–EtOH PPT. The results suggested that two-step LLE produced broader metabolome coverage than protein precipitation, and the addition of proteinase K enhanced the extraction performance further. Taken together, PK incubation combining two-step LLE of CHCl3–MeOH, followed by MeOH–H2O, was determined to be the most suitable extraction method, because of its broad metabolome coverage, high reproducibility, and satisfactory recovery. Next, the developed optimal sample preparation method was applied successfully to profile the plasma metabolome of colorectal adenoma and uncover its potential mechanism for significant differential changes in linoleic acid and phospholipid metabolism.

of genetic alterations identifies the frequent mutation of GNAS in colorectal laterally spreading tumors Dear Editor, Colorectal cancer (CRC) is among the most commonly diagnosed cancer and the leading cause of cancer-related death worldwide [1]. Most CRCs develop from adenomas. Laterally spreading tumors (LSTs) are non-polypoid superficial colorectal neoplasms (CRNs) that are larger than 1 cm and typically extend laterally along the luminal wall. Based on surface morphology, it can be classified into a granular or nongranular type. The pathological morphology of LST manifests only as adenoma or with cancer. Recent studies have characterized 45-79% of LSTs as high-grade intraepithelial neoplasia (HGIN) or submucosal invasion; and the risk of submucosal invasion increases with lesion size [2]. Hence, LST is considered a precancerous CRC lesion. Patients with LSTs are usually asymptomatic and diagnosis typically occurs during physical examinations or screening colonoscopy. However, flat tumors are difficult to detect by colonoscopy and a missed