Search

Primary sclerosing cholangitis (PSC) has been considered to be either an "autoimmune disease" or a "bile acid‐induced injury." In vitro MRS studies on PSC patients have limitations due to the contamination of bile with contrast agent (commonly administered during endoscopic retrograde cholangiopancreatography) and/or the use of patient cohorts with other diseases as controls. The objective of this study was to quantify biliary metabolites using in vivo 1H MRS and gain insight into the pathogenesis of PSC. Biliary metabolites in 10 PSC patients and 14 healthy controls were quantified in vivo using 1H MRS on a 3 T MR scanner. The concentrations of total bile acids plus cholesterol, glycine‐conjugated bile acids, taurine‐conjugated bile acids, and choline‐containing phospholipids (chol‐PLs) were compared between the two groups. There were statistically significant decreases in the levels of the above mentioned biliary metabolites in the PSC patients compared with controls. The reduction in bile acid secretion in bile of PSC patients indicates accumulation of bile acids in hepatocytes. Moreover, reduction in the levels of chol‐PLs in bile may increase the toxic effects of bile acids. Our findings suggest that the bile duct injury in PSC patients is most likely due to "bile acid‐induced injury." [ABSTRACT FROM AUTHOR]

Serum metabolites of healthy controls and esophageal cancer (EC) patients have previously been compared to predict cancer-specific profiles. However, the association between metabolic alterations in serum samples and esophageal tissues in EC patients remains unclear. Here, we analyzed 50 pairs of EC tissues and distant noncancerous tissues, together with patient-matched serum samples, using 1 H NMR spectroscopy and pattern recognition algorithms. EC patients could be differentiated from the controls based on the metabolic profiles at tissue and serum levels. Some overlapping discriminatory metabolites, including valine, alanine, glucose, acetate, citrate, succinate and glutamate, were identified in both matrices. These results suggested deregulation of metabolic pathways, and potentially revealed the links between EC and several metabolic pathways, such as the tricarboxylic acid cycle, glutaminolysis, short-chain fatty acid metabolism, lipometabolism and pyruvate metabolism. Perturbation of the pyruvate metabolism was most strongly associated with EC progression. Consequently, an optimal serum metabolite biomarker panel comprising acetate and pyruvate was developed, as these two metabolites are involved in pyruvate metabolism, and changes in their serum levels were significantly correlated with alterations in the levels of some other esophageal tissue metabolites. In comparison with individual biomarkers, this panel exhibited better diagnostic efficiency for EC, with an AUC of 0.948 in the test set, and a good predictive ability of 82.5% in the validation set. Analysis of key genes related to pyruvate metabolism in EC patients revealed patterns corresponding to the changes in serum pyruvate and acetate levels. These correlation analyses demonstrate that there were distinct metabolic characteristics and pathway aberrations in the esophageal tumor tissue and in the serum. Changes in the serum metabolic signatures could reflect the alterations in the esophageal tumor profile, thereby emphasizing the importance of distinct serum metabolic profiles as potential noninvasive biomarkers for EC., (© 2021 John Wiley & Sons, Ltd.)

Previous studies have compared fecal metabolites from healthy and colorectal cancer (CRC) patients to predict the pro-CRC signatures. However, the systemic mechanistic link between feces and colonic tissues of CRC patients is still limited. The current study was a paralleled investigation of colonic tumor tissues and their normal adjacent tissues alongside patient-matched feces by using 1 H nuclear magnetic resonance spectroscopy combined with pattern recognition to investigate how fecal metabolic phenotypes are linked to the changes in colorectal tumor profiles. A set of overlapping discriminatory metabolites across feces and tumor tissues of CRC were identified, including elevated levels of lactate, glutamate, alanine, succinate and reduced amounts of butyrate. These changes could indicate the networks for metabolic pathway perturbations in CRC potentially involved in the disruptions of glucose and glycolytic metabolism, TCA cycle, glutaminolysis, and short chain fatty acids metabolism. Furthermore, changes in fecal acetate were positively correlated with alterations of glucose and myo-inositol in colorectal tumor tissues, implying enhanced energy production for rapid cell proliferation. Compared to other fecal metabolites, acetate demonstrated the highest diagnostic performance for diagnosing CRC, with an AUC of 0.843 in the training set, and a good predictive ability in the validation set. Overall, these associations provide evidence of distinct metabolic signatures and metabolic pathway disturbances between the colonic tissues and feces within the same individual, and changes of fecal metabolic signature could reflect the CRC tissue microenvironment, highlighting the significance of the distinct fecal metabolic profiles as potential novel and noninvasive relevant indicators for CRC detection., (© 2019 UICC.)

Objectives: Lung cancer is one of the most lethal cancers. Currently, there are no biomarkers for early detection, monitoring treatment response, and detecting recurrent lung cancer. We undertook this study to determine if 1 H magnetic resonance spectroscopy (MRS) of sputum and exhaled breath condensate (EBC), as a noninvasive tool, can identify metabolic biomarkers of lung cancer., Materials and Methods: Sputum and EBC samples were collected from 20 patients, comprising patients with pathologically confirmed non-small cell lung cancer ( n = 10) and patients with benign respiratory conditions ( n = 10). Both sputum and EBC samples were collected from 18 patients; 2 patients provided EBC samples only. 1 H MR spectra were obtained on a Bruker Avance 400 MHz nuclear magnetic resonance (NMR) spectrometer. Sputum samples were further confirmed cytologically to distinguish between true sputum and saliva., Results: In the EBC samples, median concentrations of propionate, ethanol, acetate, and acetone were higher in lung cancer patients compared to the patients with benign conditions. Median concentration of methanol was lower in lung cancer patients (0.028 mM) than in patients with benign conditions (0.067 mM; P = 0.028). In the combined sputum and saliva and the cytologically confirmed sputum samples, median concentrations of N -acetyl sugars, glycoprotein, propionate, lysine, acetate, and formate were lower in the lung cancer patients than in patients with benign conditions. Glucose was found to be consistently absent in the combined sputum and saliva samples (88%) as well as in the cytologically confirmed sputum samples (86%) of lung cancer patients., Conclusion: Absence of glucose in sputum and lower concentrations of methanol in EBC of lung cancer patients discerned by 1 H MRS may serve as metabolic biomarkers of lung cancer for early detection, monitoring treatment response, and detecting recurrence., Competing Interests: Authors disclose no potential conflicts of interest.

Background and Purpose: Poor treatment outcome remains high in patients with squamous cell carcinoma (SCC) of the head and neck region. Treatment of head and neck cancer could be improved and perhaps standardized if reliable markers for tumor progression and poor prognosis could be developed. MR spectroscopy has been used previously to differentiate between malignant and adjacent normal specimen in these cancers. This study explores the capability of MR spectroscopy in providing an indication of the aggressiveness of a tumor and its response to treatment., Methods: Thirty-six SCC patients with treatment failure, and 22 other patients who were treated concurrently at the same center but with no indication of failure for a period of 3 years, were selected for the study. Tumor specimens were kept frozen at -70 degrees C, and later subjected to 1H-MR spectroscopy at 25 degrees C. The resonance areas for 6 spectral regions were determined, and their ratio calculated. The mean values of the ratios were then compared between the 2 groups by using the Student t test., Results: The choline-to-creatine (3.2/3.0 parts per million [ppm]) and the 1.3/0.9 ppm spectral intensity ratios (signal due to lipid or lactic acid) were the 2 most notable ones to be significantly elevated in the group with poor response. Using these ratios, a sensitivity of 83% and a specificity of 82% were obtained in predicting which head and neck cancer patients would fail treatment., Conclusions: These preliminary results suggest that MR spectroscopy has the potential to contribute to an accurate and early prediction of tumor behavior and response to treatment in squamous cell carcinoma of the head and neck region.