scholarly journals Mir-421 in plasma as a potential diagnostic biomarker for precancerous gastric lesions and early gastric cancer

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.

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.


2019 ◽  
Author(s):  
Yaodong Zhu ◽  
Lei Liu ◽  
Qiang Peng ◽  
He Ba ◽  
Wanji Song ◽  
...  

Abstract Background Programmed cell death 4 (PDCD4) as a newly identified tumor suppressor is involved in inhibiting tumorigenesis and tumor progression. Epithelial mesenchymal Transition (EMT) is also associated with tumorgenesis of gastric cancer. However, few studies have elucidated the role of PDCD4 in regulation of EMT during precancerous gastric lesions (PLGC) and early gastric cancer. Methods In this study, the expression of PDCD4 and EMT-associated proteins in PLGC and early gastric cancer tissues were detected by immunohistochemistry. The relationship between the expression of PDCD4 and EMT-associated proteins and clinical and pathological parameters were analyzed. The PDCD4 high-expressed SGC-7901 cell line was also used to evaluate the function of PDCD4 in vitro and in vivo. Results PDCD4 and EMT associated proteins expression were significantly altered in PLGC and early gastric cancer tissues. After transfection with the PDCD4 gene, the expression of E-cadherin was significantly increased, the expression of N-cadherin and Vimentin were also remarkably inhibited. PDCD4 high-expressed also inhibited tumor growth and pathological features in nude mice xenograft model. Conclusion This study elucidates a regulatory role of PDCD4 in PLGC and early gastric cancer and provide insights into EMT-associated target which may provide novel therapeutic recourse.


EBioMedicine ◽  
2021 ◽  
Vol 74 ◽  
pp. 103714
Author(s):  
Xue Li ◽  
Nai-Ren Zheng ◽  
Lin-Heng Wang ◽  
Zhong-Wu Li ◽  
Zong-Chao Liu ◽  
...  

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.


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Zhaoji Pan ◽  
Yiqing Tian ◽  
Guoping Niu ◽  
Chengsong Cao

Mesenchymal stem cells (MSCs) have been declared to not only participate in wound repair but also affect tumor progression. Tumor-associated MSCs, directly existing in the tumor microenvironment, play a critical role in tumor initiation, progression, and development. And different tumor-derived MSCs have their own unique characteristics. In this review, we mainly describe and discuss recent advances in our understanding of the emerging role of gastric cancer-derived MSC-like cells (GC-MSCs) in regulating gastric cancer progression and development, as well as the bidirectional influence between GC-MSCs and immune cells of the tumor microenvironment. Moreover, we also discuss the potential biomarker and therapeutic role of GC-MSCs. It is anticipated that new and deep insights into the functionality of GC-MSCs and the underlying mechanisms will promote the novel and promising therapeutic strategies against gastric cancer.


2019 ◽  
Vol 244 (12) ◽  
pp. 953-959 ◽  
Author(s):  
Wei Deng ◽  
Yulong Zhang ◽  
Jun Cai ◽  
Jun Zhang ◽  
Xiaoye Liu ◽  
...  

Metastasis is the most challenging issue for gastric cancer, and identification of the molecular mechanism and suitable targets for treatment is the major purpose of recent research. In this study, we found the long non-coding RNA ANRIL was critical for the progression of gastric cancer. Knockdown of ANRIL (also known as CDKN2B-AS) with shRNA increased apoptosis, inhibited tumor growth, and suppressed migration of cancer cells. TET2 (Tet Methylcytosine Dioxygenase 2), a methylcytosine dioxygenase suppressed ANRIL function and prevented cancer progression. Patients with higher TET2 expression survived better, while with higher ANRIL survived worse. Furthermore, expressions of TET2 and ANRIL were negatively correlated in the patient samples. The mechanistic study suggested that ANRIL promoted tumor progression mainly by enhancing NF-kB signaling. Impact statement Gastric cancer is one of the leading causes of cancer-related death. The lack of curative therapeutic options ascribes to the complex genetic background and heterogeneity of gastric cancer. Understanding the molecular details of the disease and identifying the therapeutic targets would offer additional treatment options. Long non-coding RNA ANRIL was involved in the progression of many cancers, including gastric cancer, but the mechanism was unknown. The current study indicated that ANRIL supported tumor cell survival by inhibiting apoptosis and promoted metastasis by enhancing NF-kB signaling. NF-kB signaling was critical in tumor progression, and this study proved another long non-coding RNA that could regulate NF-kB signaling. ANRIL would be a potential biomarker and therapeutic target for gastric cancer prognosis and treatment.


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