scholarly journals Striking heterogeneity of somatic L1 retrotransposition in single normal and cancerous gastrointestinal cells

2020 ◽  
Vol 117 (51) ◽  
pp. 32215-32222 ◽  
Author(s):  
Katsumi Yamaguchi ◽  
Alisha O. Soares ◽  
Loyal A. Goff ◽  
Anjali Talasila ◽  
Jungbin A. Choi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Cells ◽  
Single Cell Analysis ◽  
Single Cells ◽  
Variable Number ◽  
Normal Tissues ◽  
Modified Method ◽  
Cellular Environment ◽  
Large Numbers ◽  
Cancer Tissues

Somatic LINE-1 (L1) retrotransposition has been detected in early embryos, adult brains, and the gastrointestinal (GI) tract, and many cancers, including epithelial GI tumors. We previously found numerous somatic L1 insertions in paired normal and GI cancerous tissues. Here, using a modified method of single-cell analysis for somatic L1 insertions, we studied adenocarcinomas of colon, pancreas, and stomach, and found a variable number of somatic L1 insertions in tumors of the same type from patient to patient. We detected no somatic L1 insertions in single cells of 5 of 10 tumors studied. In three tumors, aneuploid cells were detected by FACS. In one pancreatic tumor, there were many more L1 insertions in aneuploid than in euploid tumor cells. In one gastric cancer, both aneuploid and euploid cells contained large numbers of likely clonal insertions. However, in a second gastric cancer with aneuploid cells, no somatic L1 insertions were found. We suggest that when the cellular environment is favorable to retrotransposition, aneuploidy predisposes tumor cells to L1 insertions, and retrotransposition may occur at the transition from euploidy to aneuploidy. Seventeen percent of insertions were also present in normal cells, similar to findings in genomic DNA from normal tissues of GI tumor patients. We provide evidence that: 1) The number of L1 insertions in tumors of the same type is highly variable, 2) most somatic L1 insertions in GI cancer tissues are absent from normal tissues, and 3) under certain conditions, somatic L1 retrotransposition exhibits a propensity for occurring in aneuploid cells.

scholarly journals The expression and clinical significance of PDCD4 and Her-2 in human gastric cancer

2019 ◽  
Vol 17 ◽  
pp. 205873921982823
Author(s):  
Yuelou Yang ◽  
Xiangjun Jiang ◽  
Dong Li ◽  
Feiyan Wang ◽  
Qun Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Protein Expression ◽  
Western Blot ◽  
Clinical Significance ◽  
Normal Mucosa ◽  
Normal Tissues ◽  
Positive Rate ◽  
Her 2 ◽  
Cancer Tissues ◽  
Pdcd4 Protein

To investigate the correlation and clinical significance between programmed cell death factor 4 (PDCD4) and epidermal growth factor receptor 2 (Her-2) expressions and clinicopathological parameters in patients with gastric cancer, a total of 65 cases of gastric cancer and the corresponding normal mucosa with PDCD4 and Her-2 protein expressions were detected by SP immunohistochemical staining, and 50 cases of gastric cancer and the corresponding normal mucosa with PDCD4 and Her-2 protein expression quantities were detected by Western blot, in order to analyze the relationship between the positive expressions of PDCD4 and Her-2 protein and the clinicopathological features of patients with gastric cancer. The results showed that the positive rate of PDCD4 protein expression in gastric cancer tissues was 7.7%, which was significantly lower than that in the corresponding normal tissues, that is, 77.5% ( P < 0.05); the positive rate of Her-2 expression was 41.5%, which was significantly higher than that of the corresponding normal tissues, which is 2.5% ( P < 0.05). The Western blot test showed that the expression of PDCD4 protein in gastric cancer was 0.3105 ± 0.0073, which was significantly lower than that in the corresponding normal tissues, that is, 0.9428 ± 0.0127 ( P < 0.05); the expression level of Her-2 protein in gastric cancer tissues was 0.9428 ± 0.0127, which was significantly higher than that of the corresponding normal mucosa, which is 0.2054 ± 0.0264 ( P < 0.05). The positive expressions of PDCD4 (5/65) and Her-2 (27/65) were significantly correlated with the differentiation degrees and TNM stages of gastric cancer ( P < 0.05). However, no significant correlation can be observed from Table 2 ( P > 0.05), regarding sex, age, tumor size, and lymph node metastasis. Our research claimed that PDCD4 and Her-2 may play an important role in the invasion and metastasis of gastric cancer, which has a negative correlation with biological behaviors of gastric cancer. The low expression of PDCD4 and the high expression of Her-2 in gastric cancer may promote the occurrence and progression of cancer. The PDCD4 and Her-2 test can be used as an index to evaluate the malignant biological behaviors of gastric cancer and prognosis, and provide a theoretical basis for targeted therapy.

High-Expression HBO1 Predicts Poor Prognosis in Gastric Cancer

2019 ◽  
Vol 152 (4) ◽  
pp. 517-526 ◽  
Author(s):  
Yan Wang ◽  
Sufang Chen ◽  
Wei Tian ◽  
Qing Zhang ◽  
Chunyi Jiang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Messenger Rna ◽  
Origin Recognition Complex ◽  
Tnm Staging ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Serum Carcinoembryonic Antigen ◽  
Polymerase Chain ◽  
Cancer Tissues ◽  
Kaplan Meier Plotter

Abstract Objectives Our goal was to assess the expression of histone acetyltransferase binding to origin recognition complex 1 (HBO1) in gastric cancer and the effect on prognosis for the patients. Methods We used quantitative reverse transcription polymerase chain reaction, Western blot, and tissue microarray immunohistochemistry to investigate the expressions of HBO1 messenger RNA (mRNA) and protein in gastric cancer tissues. Online resources, including Oncomine and Kaplan-Meier Plotter, were used to further assess the correlation between HBO1 expression and the prognosis of the patients with gastric cancer. Results HBO1 mRNA and protein expressions in gastric cancer tissues were both significantly higher than those in normal tissues. The correlations between high HBO1 expression and differentiation, invasive depth (T), lymph node metastasis (N), distant metastasis (M), TNM staging, and serum carcinoembryonic antigen levels were positive. High HBO1 expression was negatively correlated with survival time in patients with gastric cancer. Conclusions HBO1 might be a valuable biomarker to evaluate the prognosis of patients with gastric cancer.

scholarly journals Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation

2021 ◽  
Author(s):  
yinggang hua ◽  
yanling liu ◽  
long li ◽  
guoyan liu
Keyword(s):  
Gastric Cancer ◽  
Dna Methylation ◽  
Promoter Region ◽  
Methylation Status ◽  
Diffuse Gastric Cancer ◽  
Normal Tissues ◽  
The Difference ◽  
Diffuse Type Gastric Cancer ◽  
Cancer Tissues ◽  
Erk Signal Pathway

Abstract Background P2RY1 receptor is known to cause cancer by activating the ERK signal pathway, its DNA methylation status or even the corresponding regulatory mechanism remains unknown. Methods In this study, DNA methylation chip was used to profile the genome-wide DNA methylation level in gastric cancer tissues. Then validated by the bioinformatics analysis in the TCGA database, Immunohistochemistry staining data obtained from the HPA database to verify the difference in protein expression between normal tissues and tumor tissues . Results The promoter region of P2RY1 was found to be highly methylated with 4 hypermethylated sites (|Δβ value| >0.2) in diffuse gastric cancer and the expression level of P2RY1 is relatively low compared with non-cancerous tissues. We also showed that MRS2365, a selective agonist of the P2RY1 receptor, can induce phosphorylation of ERK1/2, inhibit cell proliferation/migration and induce apoptosis. Conclusion High DNA methylation in the promoter region of P2RY1 may have contributed to the reduced expression of P2RY1’s mRNA, which is likely responsible for the “aggressive” nature of the diffuse type gastric cancer.

scholarly journals Identification of Potential Biomarkers and Therapy Targets involved in Gastric Cancer Using Bioinformatics Analysis

2021 ◽  
Author(s):  
YangYang Teng ◽  
Na Shan ◽  
GuangRong Lu ◽  
LeYi Ni ◽  
ZeJun Gao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Bioinformatics Analysis ◽  
Risk Model ◽  
Malignant Tumors ◽  
Differentially Expressed ◽  
Hub Genes ◽  
Normal Tissues ◽  
Therapy Targets ◽  
Selection Operator ◽  
Cancer Tissues

Abstract Gastric cancer remains one of the five major malignant tumors in the world, posing a great threat to public life and health. As gene sequencing technology develops, it is urgent to find out specific molecular markers for cancer therapy. In this study, datasets of GSE13911, GSE30727, GSE63089 and GSE118916 were investigated by bioinformatics analysis, and differentially expressed genes (DEGs) between GC tissues and normal tissues were screened for potential cancer therapeutic targets. Furthermore, the GSE63089 dataset was analyzed by Weighted Gene Co-expression Network Analysis (WGCNA), and the highly related genes were clustered. Then, the hub genes were searched using co-expression network and Molecular Complex Detection (MCODE) plug-in from Cytoscape software. Finally, ASPM, COL11A1 and CDC20 were obtained by intersection of hub genes and DEGs. The expressions of ASPM, COL11A1 and CDC20 gene in gastric cancer tissues and normal tissues from TCGA database were detected. For these genes, the least absolute shrink and selection operator (LASSO) Cox expression analysis was used to establish the prognostic risk model. COL11A1 and CDC20 genes were identified as candidate prognostic risk markers for GC. Analysis using qRT-PCR has shown that COL11A1 and CDC20 were significant differentially expressed between gastric cancer tissues and normal gastric tissues (P < 0.01). In conclusion, our study identifies specific DEGs involved in ECM process and metabolism by cytochrome P450 process, and these DEGs may be potential targets for GC therapy. The model constructed by COL11A1 and CDC20 genes can predict the prognosis risk of GC patients. Taken together, these findings provide reference for further analyses of key alterations during GC progression.

scholarly journals Quantitative Detection of miRNA-21 Expression in Tumor Cells and Tissues Based on Molecular Beacon

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Qingxin Liu ◽  
Jialong Fan ◽  
Chuang Zhou ◽  
Liqun Wang ◽  
Bin Zhao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Cells ◽  
Molecular Beacon ◽  
Quantitative Detection ◽  
Fluorescence Signal ◽  
Good Prospect ◽  
Significant Difference ◽  
Degree Of Malignancy ◽  
Cancer Tissues ◽  
Different Origins

As a new tumor marker, the microRNA-21 (miRNA21) level can provide important information for early diagnosis, drug treatment, and prognosis of gastric cancer. With the tool of molecular beacons which can hybridize specifically with target miRNA-21 and generate fluorescence signal change, this paper develops a direct, simple, and rapid method for miRNA-21 detection with detection limit of 0.5 nM. Under the optimal conditions, the method was used to detect the expression of miRNA-21 in tumor cells and tissues. The results showed significant differences of miRNA-21 levels in tumor cells which have different origins and different degree of malignancy. In 8 cases of gastric cancer tissues and adjacent tissues, the level of miRNA-21 in 6 cases was higher than that in adjacent tissues, 1 case had lower expression level than that in adjacent tissues, and 1 case had no significant difference. Furthermore, qRT-PCR method was used to verify the detection results based on the fluorescent probe detection method. The consistent results show that the molecular beacon assay has a good prospect in direct and rapid detection of miRNA-21 expression and will be widely used in the functional research and clinical diagnosis of microRNA.

scholarly journals Combined bioinformatics technology to explore pivot genes and related clinical prognosis in the development of gastric cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jiasheng Xu ◽  
Xinlu Wang ◽  
Qiwen Ke ◽  
Kaili Liao ◽  
Yanhua Wan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Stage ◽  
Ppi Network ◽  
Clinical Prognosis ◽  
Normal Tissues ◽  
Cancer Related Gene ◽  
Key Genes ◽  
Cancer Tissues ◽  
Differential Genes ◽  
Development Of Gastric Cancer

AbstractTo screen the key genes in the development of gastric cancer and their influence on prognosis. The GEO database was used to screen gastric cancer-related gene chips as a training set, and the R packages limma tool was used to analyze the differential genes expressed in gastric cancer tissues compared to normal tissues, and then the selected genes were verified in the validation set. The String database was used to calculate their Protein–protein interaction (PPI) network, using Cytoscape software's Centiscape and other plug-ins to analyze key genes in the PPI network. The DAVID database was used to enrich and annotate gene functions of differential genes and PPI key module genes, and further explore correlation between expression level and clinical stage and prognosis. Based on clinical data and patient samples, differential expression of key node genes was verified by immunohistochemistry. The 63 characteristic differential genes screened had good discrimination between gastric cancer and normal tissues, and are mainly involved in regulating extracellular matrix receptor interactions and the PI3k-AKT signaling pathway. Key nodes in the PPI network regulate tumor proliferation and metastasis. Analysis of the expression levels of key node genes found that relative to normal tissues, the expression of ITGB1 and COL1A2 was significantly increased in gastric cancer tissues, and patients with late clinical stages of tumors had higher expression of ITGB1 and COL1A2 in tumor tissues, and their survival time was longer (P < 0.05). This study found that ITGB1 and COL1A2 are key genes in the development of gastric cancer and can be used as prognostic markers and potential new targets for gastric cancer.

Expression of Activating Protein 4 and Its Relationships with Prognosis in Gastric Cancer

Chemotherapy ◽  
2017 ◽  
Vol 62 (3) ◽  
pp. 181-186 ◽  
Author(s):  
Xiuwei Sun ◽  
Zhanjun Feng ◽  
Yao Qu ◽  
Jiayue Shao ◽  
Ning Wei
Keyword(s):  
Gastric Cancer ◽  
Tumor Differentiation ◽  
Invasion Depth ◽  
Normal Tissues ◽  
Node Metastasis ◽  
Patient Gender ◽  
Positive Expression ◽  
Differentiation Degree ◽  
Expression Rate ◽  
Cancer Tissues

Objective: The aim of this work was to investigate the expression of transcription activating protein 4 (AP-4) in gastric cancer (GC) and its impacts on prognosis. Methods: The cancer tissues and normal tissues of 54 GC patients were sampled for the expression detection of AP-4, and the patients were followed up. Results: The positive expression rate of AP-4 in the cancer tissues (68.5%) was higher than the normal tissues (22.2%; p < 0.01). The lower the tumor differentiation degree and the deeper the invasion depth, the higher the expression rate of AP-4. The median survival time of the patients with positive AP-4 expression was significantly shorter than of those without AP-4 expression (26.3/41.3 months), and the accumulative survival rate of the former was also lower than the latter (χ2 = 4.736, p = 0.03). AP-4 was expressed in GC tissues and normal gastric tissues, with the expression in the former being higher. Conclusions: The expression of AP-4 was positively related with the tumor differentiation degree, invasion depth, lymph node metastasis, and pTNM stage, while it was not related with patient gender, age, tumor size, location, or distant metastasis. AP-4 might be used as an indicator for the prognosis prediction of GC.

scholarly journals Identification of Aberrantly Expressed miRNAs in Gastric Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Dan Liu ◽  
Xiaowei Hu ◽  
Hongfeng Zhou ◽  
Guangyue Shi ◽  
Jin Wu
Keyword(s):  
Gastric Cancer ◽  
Gene Ontology ◽  
Real Time ◽  
Real Time Pcr ◽  
Malignant Disease ◽  
Gene Ontology Analysis ◽  
Normal Tissues ◽  
Therapy Targets ◽  
New Perspective ◽  
Cancer Tissues

The noncoding components of the genome, including miRNA, can contribute to pathogenesis of gastric cancer. Their expression has been profiled in many human cancers, but there are a few published studies in gastric cancer. It is necessary to identify novel aberrantly expressed miRNAs in gastric cancer. In this study, the expression profile of 1891 miRNAs was analyzed using a miRCURY array LNA miRNA chip from three gastric cancer tissues and three normal tissues. The expression levels of 4 miRNAs were compared by real-time PCR between cancerous and normal tissues. We found that 31 miRNAs are upregulated in gastric cancer(P<0.05)and 10 miRNAs have never been reported by other studies; 30 miRNA are downregulated(P<0.05)in gastric cancer tissues. Gene ontology analysis revealed that those dysregulated miRNAs mainly take part in regulating cell proliferation. The levels of has-miR-105, -213*, -514b, and -548n were tested by real-time PCR and have high levels in cancerous tissues. Here, we report a miRNA profile of gastric cancer and provide new perspective to understand this malignant disease. This novel information suggests the potential roles of these miRNAs in the diagnosis, prognosis biomarkers, or therapy targets of gastric cancer.

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