scholarly journals Dissecting expression profiles of gastric precancerous lesions and early gastric cancer to explore crucial molecules in intestinal‐type gastric cancer tumorigenesis

2020 ◽  
Vol 251 (2) ◽  
pp. 135-146
Author(s):  
Yajing Zhang ◽  
Xi Wu ◽  
Chengli Zhang ◽  
Jiaqi Wang ◽  
Guijun Fei ◽  
...  
2020 ◽  
Author(s):  
Xiaotao Jiang ◽  
Kunhai Zhuang ◽  
Kailin Jiang ◽  
Yi Wen ◽  
Linling Xie ◽  
...  

Abstract Background Immune microenvironment in gastric precancerous lesions (GPL) and early gastric cancer (EGC) still remain largely unknown. This study aims to identify key immune cells and hub genes associated with GPL progression to EGC. Methods Immune Cell Abundance Identifier (ImmuCellAI) algorithm was used to quantify the proportions of immune cells of GPL and GC samples based on gene expression profiles. Key immune cells associated with GPL progression to EGC were identified using one‐way analysis of variance (ANOVA) test and Spearman’s correlation test. Weighted gene co-expression analysis (WGCNA) and pathway enrichment were adopted to identify hub gene co-expression network and hub genes associated with the key immune cells infiltration. The pattern of key immune cells infiltration, hub genes expression and their correlation were verified in an independent GPL-EGC cohort and GC datasets.Results NKT cell was found gradually decreased during GPL progression to EGC and negatively correlated with tumorigenesis. According to WGCNA and hub genes screening, CXCR4, having a poor prognosis, increased with GPL progression, positively correlated with tumorigenesis and negatively correlated with NKT cell infiltration significantly, was identified as the real hub gene. The negative correlation between CXCR4 and NKT cell infiltration was successfully verified in an independent GPL-EGC cohort and GC datasets.Conclusion CXCR4 and NKT cell are possible to serve as biomarkers in monitoring GPL progression to EGC. Besides, CXCR4 may be involved in regulating NKT cell infiltration during GPL progression to EGC, which may provide a new immunotherapeutic target.


2021 ◽  
Author(s):  
Seiichiro Abe ◽  
Juntaro Matsuzaki ◽  
Kazuki Sudo ◽  
Ichiro Oda ◽  
Hitoshi Katai ◽  
...  

Abstract Background The aim of this study was to identify serum miRNAs that discriminate early gastric cancer (EGC) samples from non-cancer controls using a large cohort. Methods This retrospective case–control study included 1417 serum samples from patients with EGC (seen at the National Cancer Center Hospital in Tokyo between 2008 and 2012) and 1417 age- and gender-matched non-cancer controls. The samples were randomly assigned to discovery and validation sets and the miRNA expression profiles of whole serum samples were comprehensively evaluated using a highly sensitive DNA chip (3D-Gene®) designed to detect 2565 miRNA sequences. Diagnostic models were constructed using the levels of several miRNAs in the discovery set, and the diagnostic performance of the model was evaluated in the validation set. Results The discovery set consisted of 708 samples from EGC patients and 709 samples from non-cancer controls, and the validation set consisted of 709 samples from EGC patients and 708 samples from non-cancer controls. The diagnostic EGC index was constructed using four miRNAs (miR-4257, miR-6785-5p, miR-187-5p, and miR-5739). In the discovery set, a receiver operating characteristic curve analysis of the EGC index revealed that the area under the curve (AUC) was 0.996 with a sensitivity of 0.983 and a specificity of 0.977. In the validation set, the AUC for the EGC index was 0.998 with a sensitivity of 0.996 and a specificity of 0.953. Conclusions A novel combination of four serum miRNAs could be a useful non-invasive diagnostic biomarker to detect EGC with high accuracy. A multicenter prospective study is ongoing to confirm the present observations.


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.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lihua Chu ◽  
Jialian Zhao ◽  
Cheng Sheng ◽  
Min Yue ◽  
Feifei Wang ◽  
...  

Abstract Background Confocal laser endomicroscopy (CLE) has advantages in detecting gastric neoplastic lesions, meanwhile it requires strict patient cooperation. Sedation could improve patient cooperation and quality of endoscopy. However, sedation is still not very popular in some resource-limited countries and regions. The purpose of this study was to compare propofol-based sedated versus un-sedated CLE in the value of diagnosing early gastric cancer (EGC) and precancerous lesions. Methods A retrospective, cohort, single center study of 226 patients who underwent CLE between January 1, 2015 and December 31, 2017 was performed. Patients enrolled were allocated into the propofol-based sedated group (n = 126) and the un-sedated group (n = 100). The comparison of validity and reliability of CLE for identifying EGC and precancerous lesions between the two groups was performed through analyzing CLE diagnosis and pathological diagnosis. Reporting followed the STROBE guidelines. Results The area under receiver operating characteristic curve (AUROC) of diagnosing EGC in the sedated group was 0.97 (95 % CI: 0.95 to 0.99), which was higher than that in the un-sedated group (0.88 (95 % CI: 0.80 to 0.97), P = 0.0407). CLE with sedation performed better than without sedation in diagnosing intraepithelial neoplasia and intestinal metaplasia (P = 0.0008 and P = 0.0001, respectively). For patients considered as high-grade intraepithelial neoplasia or EGC by endoscopists, they would not get biopsy during CLE but receive endoscopic submucosal dissection (ESD) subsequently, and the misdiagnosis rate of CLE was 0 % in the sedated group and 27.59 % (95 % CI: 10.30–44.91 %) in the un-sedated group (P = 0.006). Conclusions Propofol based sedation was associated with improved diagnostic value of CLE for detecting EGC as well as precancerous lesions (intraepithelial neoplasia OR intestinal metaplasia).


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