scholarly journals HypermethylatedFAM5CandMYLKin Serum as Diagnosis and Pre-Warning Markers for Gastric Cancer

2012 ◽  
Vol 32 (3) ◽  
pp. 195-202 ◽  
Author(s):  
Lu Chen ◽  
Liping Su ◽  
Jianfang Li ◽  
Yanan Zheng ◽  
Beiqin Yu ◽  
...  

Most cases of gastric cancer (GC) are not diagnosed at early stage which can be curable, so it is necessary to identify effective biomarkers for its diagnosis and pre-warning. We have used methylated DNA immunoprecipitation (MeDIP) to identify genes that are frequently methylated in gastric cancer cell lines. Promoter regions hypermethylation of candidate genes were tested by methylation-specific polymerase chain reaction (MSP) in serum samples, including GC (n= 58), gastric precancerous lesions (GPL,n= 46), and normal controls (NC,n= 30). Eighty two hypermethylated genes were acquired by array analysis and 5 genes (BCAS4, CHRM2, FAM5C, PRACandMYLK) were selected as the candidate genes. Three genes (CHRM2, FAM5CandMYLK) were further confirmed to show methylation rates increased with progression from NC to GPL, then to GC. There was obvious decrease in detection ofFAM5CandMYLKhypermethylation, but notCHRM2, from preoperative to postoperative evaluation (P< 0.001). Combined detection of FAM5C and MYLK hypermethylation had a higher sensitivity in GC diagnosis (77.6%,45/58) and pre-warning (30.4%,14/46) than one single gene detection and also had a high specificity of 90%. The combined hypermethylated status ofFAM5CandMYLKcorrelated with tumor size (P< 0.001), tumor invasion depth (P= 0.001) and tumor-node-metastasis (TNM) stage (P= 0.003). HypermethylatedFAM5CandMYLKcan be used as potential biomarkers for diagnosis and pre-warning of GC.

2020 ◽  
Author(s):  
Xin Ge ◽  
Xiaolei Zhang ◽  
Yanling Ma ◽  
Shaohua Chen ◽  
Zhaowu Chen ◽  
...  

Abstract BACKGROUND Early diagnosis is very important to improve the survival rate of patients with gastric cancer, especially in asymptomatic participants. However, low sensitivity of common biomarkers has caused difficulties in early screening of gastric cancer. In this study, we explored whether MIC-1 can improve the detection rate of early gastric cancer.METHODS We screened 8,257 participants based on risk factors such as age, gender, and family history for physical examination including gastroscopy. Participant blood samples were taken for measure MIC-1, CA-199, CA72-4 and PG1/PG2 levels. The diagnostic performance of MIC-1 was assessed and compared with CA-199, CA72-4 and PG1/PG2, and its role in early gastric cancer diagnosis and the assessment of the risk of precancerous lesions have also been studied.RESULTS Based on endoscopic and histopathological findings, 55 participants had gastric cancer, 566 participants had low-grade neoplasia, 2605 participants had chronic gastritis. MIC-1 levels were significantly elevated in gastric cancer serum samples as compared to controls (p<0.001). The sensitivity of serum MIC-1 for gastric cancer diagnosis was much higher than that of CA-199 (49.1% vs. 20.0%) with similar specificities. Moreover, receiver operating characteristic (ROC) curve analysis also showed that serum MIC-1 had a better performance compared with CA-199, CA72-4 and PG1/PG2 in distinguishing early-stage gastric cancer (AUC: 72.9% vs. 69.5%, 67.5%, 44.0% respectively).CONCLUSIONS Serum MIC-1 is significantly elevated in most patients with early gastric cancer. MIC-1 can serve as a novel diagnostic marker of early gastric cancer and value the risk of gastric cancer.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 410-410 ◽  
Author(s):  
Yu Jin Kim ◽  
Won Shik Kim ◽  
Sang Woo Kim ◽  
Woon Yong Jung

410 Background: In our previous study, we identified three miRNAs (hsa-miR-421, hsa-miR-29b-1-5p, and hsa-miR-27b-5p) with two mRNAs (FBXO11 and CREBZF) that might play an important role in the development of gastric adenocarcinoma (GAC) from premalignant adenomas. However, the expression and function of these miRNAs have not been not well characterized. Methods: We investigated the roles of CREBZF and miRNAs as potential biomarkers for the progression of gastric cancer (GC) in low-/high-grade dysplasia and early gastric cancer patients using immunohistochemical staining and miRNA in situ hybridization. Considering that targets can modulate in GC, we analyzed the CREBZF expression in gastric cancer cell lines by RT-PCR and western blot analysis. Results: We observed lower expression of CREBZF with increasing miRNAs in the MKN-74 gastric cancer cells compared to that in SNU-NCC-19. Next, the role of CREBZF in MKN-74 gastric cancer cells was investigated via cell viability and migration assays by miRNA/anti-miRNA modulation. Furthermore, we found that hsa-miR-421/hsa-miR-29b-1-5p target CREBZF and might play an important role in the migration of MKN-74 cells. Conclusions: This study suggests that increased CREBZF by hsa-miR-421/hsa-miR-29b-1-5p inhibition may be important to prevent the progression of gastric cancer in its early stage.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Wenfen Zhang ◽  
Zhenhua Tian ◽  
Shujie Yang ◽  
Joseph Rich ◽  
Shuaiguo Zhao ◽  
...  

AbstractExosomes are cell-derived nanovesicles that have recently gained popularity as potential biomarkers in liquid biopsies due to the large amounts of molecular cargo they carry, such as nucleic acids and proteins. However, most existing exosome-based analytical sensing methods struggle to achieve high sensitivity and high selectivity simultaneously. In this work, we present an electrochemical micro-aptasensor for the highly sensitive detection of exosomes by integrating a micropatterned electrochemical aptasensor and a hybridization chain reaction (HCR) signal amplification method. Specifically, exosomes are enriched on CD63 aptamer-functionalized electrodes and then recognized by HCR products with avidin-horseradish peroxidase (HRP) attached using EpCAM aptamers as bridges. Subsequently, the current signal that is generated through the enzyme reaction between the HRP enzyme and 3,3’,5,5’-tetramethylbenzidine (TMB)/H2O2 directly correlates to the amount of bound HRP on the HCR products and thus to the number of target exosomes. By introducing anti-EpCAM aptamers, micro-aptasensors can detect cancerous exosomes with high specificity. Due to the micropatterned electrodes and HCR dual-amplification strategy, the micro-aptasensors achieve a linear detection response for a wide range of exosome concentrations from 2.5×103 to 1×107 exosomes/mL, with a detection limit of 5×102 exosomes/mL. Moreover, our method successfully detects lung cancer exosomes in serum samples of early-stage and late-stage lung cancer patients, showcasing the great potential for early cancer diagnosis.


2009 ◽  
Vol 32 (11) ◽  
pp. 1936-1939 ◽  
Author(s):  
Tomoki Nakamura ◽  
Noriyuki Nakatsu ◽  
Yoko Yoshida ◽  
Kanami Yamazaki ◽  
Shingo Dan ◽  
...  

Author(s):  
Angelo Zullo ◽  
Edith Lahner ◽  
Cesare Hassan ◽  
Bruno Annibale ◽  
Gianluca Esposito

<b><i>Introduction:</i></b> Since screening programs for gastric cancer are not applicable in Western countries, identification and follow-up of gastric precancerous lesions, such as extensive intestinal metaplasia (IM), are worthwhile to increase the diagnosis of cancer at an early stage. We investigated whether an optimal age threshold to detect extensive IM in a European country exists. <b><i>Methods:</i></b> This was a post hoc analysis of prospectively collected data in a nationwide study involving consecutive patients aged between 50 and 65 years who underwent an upper endoscopy with the standard 5 gastric biopsies. The presence of extensive (antral and gastric body) IM on gastric mucosa was considered. <b><i>Results:</i></b> Data found that the prevalence of extensive IM was distinctly higher in patients aged 60–65 years, with a 2.28-fold increased probability compared to younger patients. None of the other considered factors (sex, BMI, smoking habit, first-degree family history, and symptoms) emerged as an independent predictor of extensive IM in the stomach. <b><i>Conclusion:</i></b> When deciding for an occasional gastric cancer screening in Western populations, the choice of an age range of 60–65 years might be appropriate, allowing detection of a distinctly high prevalence of extensive IM deserving scheduled follow-up.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7002 ◽  
Author(s):  
Jianlin Chen ◽  
Lihua Wu ◽  
Yifan Sun ◽  
Qi Yin ◽  
Xianhua Chen ◽  
...  

Objective MicroRNA (miR)-421 plays a key role in cancer progression. It has been reported that circulating miR-421may be a potential tumor marker for the diagnosis of several cancers. However, the role of miR-421 in plasma as a potential biomarker in the diagnosis of precancerous gastric lesions (Pre) and early-stage gastric cancer (GC) remains poorly understood. In this study, we investigated miR-421 in plasma as a novel potential biomarker for the detection of precancerous gastric lesions and early-stage (GC). Materials & Methods The miRNA content was determined by quantitative real-time polymerase chain reaction (qRT-PCR). MiR-421 content in all subjects was normalized by endogenous miRNA (miR-16). The diagnostic value of miR-421 for Pre and GC was assessed by comparing receiver operating characteristic (ROC) analysis with traditional tumor markers, including CEA, CA125, CA153, CA211 and CA50. The correlation between the expression of miR-421 and the pathological characteristics of Pre and GC was analyzed. Results Elevated expression of miR-421 in plasma can robustly distinguish the normal population from Pre and GC cases, especially in the early stages of gastric cancer cases (all p < 0.05). The ROC analyses showed that the area under the ROC curve (AUC), sensitivity, accuracy and Youden index of miR-421 were superior to traditional tumor markers (CEA, CA125, CA153, CA211, and CA50) in GC diagnosis, while its specificity was higher than CEA, CA153 and CA50 (all p < 0.05). MiR-421 in plasma had higher AUC value than AFP, CA153, CA211 and CA50 in the diagnosis of Pre (all p < 0.05), while specificity, accuracy and Youden index of miR-421 was only lower than CA211. The efficiency of miR-421 in the diagnosis of GC was significantly higher than that of CA211 and CA50, and it was significantly higher than CA153, CA211 and CA50 in the diagnosis of Pre (all p < 0.05). In addition, up-regulation of miR-421 occurred initially in precancerous gastric lesions as well as in the early stage of GC. Conclusions Overexpression of plasma miR-421 is a novel biomarker for the detection of precancerous lesions and early gastric cancer.


2017 ◽  
Vol 8 (6) ◽  
pp. 1038-1044 ◽  
Author(s):  
Zhenghua Lin ◽  
Mengzhao Luo ◽  
Xueqing Chen ◽  
Xingkang He ◽  
Yun Qian ◽  
...  

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