scholarly journals Quantitative Analysis of Methylated Adenosine Modifications Revealed Increased Levels of N6-Methyladenosine (m6A) and N6,2′-O-Dimethyladenosine (m6Am) in Serum From Colorectal Cancer and Gastric Cancer Patients

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.

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6679 ◽  
Author(s):  
Mingzhi Xie ◽  
Kezhi Li ◽  
Jilin Li ◽  
Dongcheng Lu ◽  
Bangli Hu

The role of serum serine peptidase inhibitor, Kazal type 4 (SPINK4), in colorectal cancer (CRC) is largely unknown. This study aimed to explore the association and diagnostic value of serum SPINK4 in CRC. A total of 70 preoperative CRC patients, 30 postoperative CRC patients, 30 gastric cancer patients, and 30 healthy controls were enrolled. Using enzyme-linked immunosorbent assays, we found that the serum SPINK4 level was significantly increased in preoperative CRC compared with postoperative CRC patients, gastric cancer patients, and healthy controls (p < 0.05). The serum SPINK4 level was remarkably elevated in colon cancer compared with rectal cancer and was enhanced in the M1 stage compared with the M0 stage (p < 0.05). The area under the receiver operating characteristic curve of serum SPINK4 level in the diagnosis of CRC was 0.9186, with a sensitivity and specificity of 0.886 and 0.900, respectively, and a cut-off value of 2.065. There was no significant difference between high and low expression of serum SPINK4 regarding the overall survival time and disease-free survival (p > 0.05). This study demonstrated that the serum SPINK4 level increased in CRC and was associated with the location and distant metastasis of CRC. It had a high diagnostic value in CRC but was not associated with the survival of CRC patients.


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.


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.


2014 ◽  
Vol 32 (30_suppl) ◽  
pp. 264-264
Author(s):  
Nana Nakamoto ◽  
Fumiaki Nakamura ◽  
Takahiro Higashi ◽  
Momoko Iwamoto ◽  
Asuka Amano ◽  
...  

264 Background: Health insurance claims data have been used extensively as a less labor-intensive method of collecting data than medical record reviews, which are the preferred source of data collection in most medical studies. Although recent reports have raised questions about its validity of use in measuring care quality, validity of using claims data may differ by health systems and should therefore be assessed by country. We aimed to test the validity of using claims data in Japan by comparing quality performance scores obtained from claims data to those derived from medical record reviews. Methods: We reviewed medical records from Apr 2013 to Apr 2014 of gastric and colorectal cancer patients who were diagnosed in 2011 from 4 cancer care hospitals in Okinawa. We calculated the proportion of patients who received adjuvant chemotherapy for gastric and colorectal cancer using claims data, and compared the results with those obtained from medical record reviews. Chart reviews were performed by certified tumor registrars. We used kappa coefficients to measure the level of agreement between claims data and medical record reviews. Results: Analysis using claims data resulted in 14 Stage II and III gastric cancer patients who had undergone surgery, with 50% receiving adjuvant chemotherapy; whereas medical record reviews resulted in 19 patients, 94.7% of whom either received or had a clinically valid rationale for not undergoing adjuvant therapy. For colorectal patients, claims data resulted in 48.5% of 68 surgical stage III colorectal patients receiving adjuvant therapy, compared to 74.4% of 78 patients using medical record reviews who either received adjuvant therapy or had a valid reason for not undergoing therapy. Agreement between claims data and chart reviews was low (kappa=0.14) for gastric cancer, but fair (kappa =0.37) for colorectal cancer. Conclusions: Our analysis showed that use of claims data may greatly underestimate quality performance measures if they are not compensated by medical record reviews. Claims data alone cannot capture a large proportion of patients who either choose not to, or has a clinically valid reason for not undergoing standard care.


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.


2019 ◽  
Vol 34 (3) ◽  
pp. 292-301 ◽  
Author(s):  
Michal Vočka ◽  
Daniel Langer ◽  
Vladimir Fryba ◽  
Jaromir Petrtyl ◽  
Tomas Hanus ◽  
...  

Objective: Tissue inhibitor of metalloproteinases 1 (TIMP-1) and matrix metalloproteinase 7 (MMP-7) were reported to have potent growth promoting activity. Lack of balance between MMPs and TIMPs is an important factor in the development of gastrointestinal malignancies. Methods: We collected serum samples from 97 patients with metastatic colorectal cancer and 79 samples from healthy controls. Serum levels of TIMP-1 and MMP-7 were measured immunochemically and compared with standard tumor markers carcinoembryonic antigen and CA19-9. Results: Serum levels of TIMP-1 and MMP-7 were significantly higher in patients with colorectal cancer compared to healthy controls (both, P < 0.001). TIMP-1 and MMP-7 correlate with the presence of colon involvement (P = 0.001; P = 0.012) and the presence of liver metastases (P = 0.002; P = 0.037), and negatively correlate with pulmonary metastases (P = 0.014; P = 0.005). MMP-7 had similar sensitivity and the same specificity as carcinoembryonic antigen. TIMP-1 and MMP-7 had better sensitivity than CA19-9. TIMP-1 and MMP-7 level correlate with worse outcome (P = 0.002). Conclusion: The results indicate that TIMP-1 and MMP-7 are effective biomarkers in patients with metastatic colorectal cancer with good sensitivity. TIMP-1 and MMP-7 levels strongly correlate with the extent of liver disease and have prognostic value.


Open Medicine ◽  
2015 ◽  
Vol 10 (1) ◽  
Author(s):  
Yijin Lin ◽  
Jintao Yuan ◽  
Lihui Wang ◽  
Lan Wang ◽  
Yunjia Ma ◽  
...  

AbstractBackground. Many recent studies revealed that the single nucleotide polymorphisms have considerable effects on the susceptibility of cancer, such as prostate cancer, lung cancer and gastric cancer. The E-cadherin, a calcium-dependent transmembrane glycoprotein encoded by CDH1 gene, is critical for epithelial construction, intercellular adhesion and cell migration. Some associations have been reported between single nucleotide polymorphisms and gastric cancer in the Chinese population. Objective. To investigate whether the single nucleotide polymorphism in CDH1 gene is associated with the susceptibility of gastric cancer in the Chinese population. Material and methods. The genotypes of 5 known single nucleotide polymorphisms (rs33935154, rs121964871, rs121964874, rs121964875, rs121964876) were determined in 359 gastric cancer patients and 368 healthy controls. High resolution melting curve detection and sequencing analysis were used in the present study. Results. There is a statistical significance in the rs121964871 C>G polymorphism between gastric cancer patients and healthy controls (OR=1.769, 95%CI: 1.051-2.976). Elderly male individuals (>50 years of age) carrying this risk factor may be more susceptible to gastric cancer. Conclusions. The results indicated that the rs121964871 C>G polymorphism is associated with the susceptibility of gastric cancer in the Chinese population, with some age and sex-dependent tendencies observed.


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