scholarly journals UHPLC-ESI-MS/MS Quantification of Relevant Substrates and Metabolites of the Kynurenine Pathway Present in Serum and Peritoneal Fluid from Gastric Cancer Patients—Method Development and Validation

2021 ◽  
Vol 22 (13) ◽  
pp. 6972
Author(s):  
Ilona Sadok ◽  
Katarzyna Jędruchniewicz ◽  
Karol Rawicz-Pruszyński ◽  
Magdalena Staniszewska

Metabolites and enzymes involved in the kynurenine pathway (KP) are highly promising targets for cancer treatment, including gastrointestinal tract diseases. Thus, accurate quantification of these compounds in body fluids becomes increasingly important. The aim of this study was the development and validation of the UHPLC-ESI-MS/MS methods for targeted quantification of biologically important KP substrates (tryptophan and nicotinamide) and metabolites(kynurenines) in samples of serum and peritoneal fluid from gastric cancer patients. The serum samples were simply pretreated with trichloroacetic acid to precipitate proteins. The peritoneal fluid was purified by solid-phase extraction before analysis. Validation was carried out for both matrices independently. Analysis of the samples from gastric cancer patients showed different accumulations of tryptophan and its metabolites in different biofluids of the same patient. The protocols will be used for the evaluation of tryptophan and kynurenines in blood and peritoneal fluid to determine correlation with the clinicopathological status of gastric cancer or the disease’s prognosis.

2014 ◽  
Vol 37 (4) ◽  
pp. 226 ◽  
Author(s):  
Haiyan Liu ◽  
Wenyong Wu ◽  
Yang Liu ◽  
Changle Zhang ◽  
Zheng Zhou

Purpose: Gastric cancer is associated with poor prognosis. The high mortality rate of gastric cancer is mainly attributed to late detection, so diagnosis and treatment are crucial to decreasing mortality. The purpose of this study was to examine the predictive accuracy and discriminative ability of cystic fibrosis transmembrane conductance regulator (CFTR) in gastric cancer patients, in addition to the classical cancer tumor biomarkers carbohydrate antigen 199 (CA199) and carcinoembryonic antigen (CEA). Methods: The study was performed on 78 serum samples from gastric cancer patients and 88 serum samples from healthy adults. Serum levels of CFTR, CA199, CEA and CHN were determined by enzyme-linked immunosorbent assay (ELISA) Results: Spearman’s coefficient analysis showed that, in some cases, CFTR was strongly correlated with CA199 and that CFTR levels increased with age. Kruskal-Wallis testing indicated concentrations of CFTR and CA199 had statistically significant association with stage. Logistic regression showed that CFTR and CA199 independently predicted gastric cancer. Receiver operating characteristics (ROC) showed that combinations of CFTR, CA199, and CEA yielded the best ROC curve, with an AUC of 0.875. Conclusions: The results of this study indicate that the serum CFTR has a broad application prospects for detection of GC.


Author(s):  
Yiqiu Hu ◽  
Zhihao Fang ◽  
Jiayi Mu ◽  
Yanqin Huang ◽  
Shu Zheng ◽  
...  

Colorectal cancer and gastric cancer are the most prevalent gastrointestinal malignancies worldwide, and early detection of these cancers is crucial to reduce their incidence and mortality. RNA methylation plays an important regulatory role in a variety of physiological activities, and it has drawn great attention in recent years. Methylated adenosine (A) modifications such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 2′-O-methyladenosine (Am), N6,2′-O-dimethyladenosine (m6Am), and N6,N6-dimethyladenosine (m62A) are typical epigenetic markers of RNA, and they are closely correlated to various diseases including cancer. Serum is a valuable source of biofluid for biomarker discovery, and determination of these adenosine modifications in human serum is desirable since they are emerging biomarkers for detection of diseases. In this work, a targeted quantitative analysis method using hydrophilic interaction liquid chromatography–tandem mass spectrometry (HILIC-MS/MS) was developed and utilized to analyze these methylated adenosine modifications in serum samples. The concentration differences between the healthy volunteers and cancer patients were evaluated by Mann–Whitney test, and receiver operator characteristic (ROC) curve analysis was performed to access the potential of these nucleosides as biomarkers. We demonstrated the presence of the m6Am in human serum for the first time, and we successfully quantified the concentrations of A, m6A, m1A, and m6Am in serum samples from 99 healthy controls, 51 colorectal cancer patients, and 27 gastric cancer patients. We found that the levels of m6A and m6Am in serum were both increased in colorectal cancer or gastric cancer patients, compared to that in healthy controls. These results indicate that m6A and m6Am in serum may act as potential biomarkers for early detection and prognosis of colorectal cancer and gastric cancer. In addition, the present work will stimulate investigations on the effects of adenosine methylation on the initiation and progression of colorectal cancer and gastric cancer.


2018 ◽  
Vol 17 (3) ◽  
pp. 41-50
Author(s):  
A. V. Belkovets ◽  
S. A. Kurilovich ◽  
V. N. Maksimov ◽  
Yu. I. Ragino ◽  
L. V. Scherbakova ◽  
...  

Background.A functionally significant TP53Arg72Pro polymorphism can contribute to the development of gastric cancer (GC).The aim:to study the associations of genotypes and alleles of the TP53Arg72Pro 4 polymorphism with GC and biomarkers of gastric ucosal atrophy in population-based prospective and case-control clinical trials among the population of Siberia.Material and methods.As a part of the epidemiological study, data of the international multicenter HAPIEE project for 2003–05, based on a population sample of residents of Novosibirsk city (serum and  DNA samples) and data of the population-based registry of GC  (2012) were compared. Gastric cancer patients were matched by  age and sex to HAPIEE population controls. A total of 156 serum  samples (GC – 52, control – 104) and 146 DNA samples (GC – 50,  control – 96) were available for prospective analysis. DNA samples  from 80 gastric cancer patients (45 men and 35 women, mean age  61.0 ± 13.4 years) and from 87 age-and sex-matched controls were  analyzed. DNA samples from venous blood were genotyped  according to standard methods. Serum samples were tested using  diagnostic kit for enzyme-linked immunosorbent assays to determine the levels of pepsinogen I (PGI), PGII, PGI/PGII ratio, gastrin-17 and IgG antibodies to H. pylori.Results.No differences in genotype and allele frequencies of the TP53 gene between the case group and the control group were  found. A decreased frequency of the Pro allele in female gastric  cancer patients compared with controls indicated that the Pro allele  is protective against the development of gastric cancer, but this  effect was not observed in male patients. No associations of TP53  genotypes with the risk of diffuse or intestinal gastric cancer, as well  as with the age and sex of patients were found. A high frequency of  genotypes with the Pro allele in patients with stage III–IV gastric  cancer indicated the relationship between Arg/Pro TR53 and tumor  progression, in particular, the contribution of the minor Pro allele to  the unfavorable prognosis. A prospective study showed high risk of  reducing the level of pepsinogen for assessing predisposition to  gastric cancer.Conclusion.Two case-control studies (population and clinical) conducted in the Western Siberia found no relationship between the  TP53Arg72Pro polymorphism and the risk of gastric cancer. However, the TP53 genotype with a rare Pro allele was associated with atrophic gastritis and severity of gastric cancer.


2019 ◽  
Vol 12 (02) ◽  
pp. 1950003 ◽  
Author(s):  
Liu Guo ◽  
Yuanpeng Li ◽  
Furong Huang ◽  
Jia Dong ◽  
Fucui Li ◽  
...  

This study aimed to explore the application of surface-enhanced Raman scattering (SERS) in the rapid diagnosis of gastric cancer. The SERS spectra of 68 serum samples from gastric cancer patients and healthy volunteers were acquired. The characteristic ratio method (CRM) and principal component analysis (PCA) were used to differentiate gastric cancer serum from normal serum. Compared with healthy volunteers, the serum SERS intensity of gastric cancer patients was relatively high at 722[Formula: see text]cm[Formula: see text], while it was relatively low at 588, 644, 861, 1008, 1235, 1397, 1445 and 1586[Formula: see text]cm[Formula: see text]. These results indicated that the relative content of nucleic acids in the serum of gastric cancer patients rises while the relative content of amino acids and carbohydrates decreases. In PCA, the sensitivity and specificity of discriminating gastric cancer were 94.1% and 94.1%, respectively, with the accuracy of 94.1%. Based on the intensity ratios of four characteristic peaks at 722, 861, 1008 and 1397[Formula: see text]cm[Formula: see text], CRM presented the diagnostic sensitivity and specificity of 100% and 97.4%, respectively, and the accuracy of 98.5%. Therefore, the three peak intensity ratios of I[Formula: see text]/I[Formula: see text], I[Formula: see text]/I[Formula: see text] and I[Formula: see text]/I[Formula: see text] can be considered as biological fingerprint information for gastric cancer diagnosis and can rapidly and directly reflect the physiological and pathological changes associated with gastric cancer development. This study provides an important basis and standards for the early diagnosis of gastric cancer.


2015 ◽  
Author(s):  
Jeong Min Kim ◽  
Won Suk Lee ◽  
Woo Sun Kwon ◽  
Han Na Park ◽  
Hye Rin Lee ◽  
...  

2020 ◽  
Vol 29 (5) ◽  
Author(s):  
Peng‐Fei Zhang ◽  
Ze‐Dong Du ◽  
Feng Wen ◽  
Feng‐Yi Zhang ◽  
Wei‐Han Zhang ◽  
...  

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