TP53 mutation and BUBR1 overexpression characterize the DNA aneuploidy of gastric cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15039-e15039
Author(s):  
Eiji Oki ◽  
Koji Ando ◽  
Satoshi Ida ◽  
Yasue Kimura ◽  
Hiroshi Saeki ◽  
...  

e15039 Background: Gastric cancers show a high frequency of DNA aneuploidy, which is a phenotype of chromosomal instability. Gastric carcinomas with aneuploidy have been shown to have higher proliferative activity and metastatic or invasive potential than diploid tumors, which leads to a poor prognosis. It has been suggested that an abnormal spindle assembly checkpoint is involved in DNA aneuploidy, but the underlying mechanism is still unclear. In this study, we focused on the TP53 gene and BUBR1 protein in gastric cancer to elucidate their relation with the features of DNA aneuploidy. Methods: The study included 178 unselected Japanese patients with primary gastric cancer who underwent gastrectomy between 1994 and 2006 at Kyushu University Hospital, Fukuoka. DNA ploidy status, TP53 gene status, and BUBR1 expression were analyzed. Nuclear DNA content was measured using laser scanning cytometry. The TP53 gene was amplified from exon 5 to exon 9, including exon-intron junctions, by PCR using p53 primers (Nippon Gene, Tokyo, Japan) and Ex Taq DNA polymerase (TaKaRa Bio Inc., Tokyo, Japan). Results: DNA aneuploidy was identified in 108 cases, and TP53 gene mutation was seen in 28 of 143 cases. Both DNA aneuploidy and TP53-mutated tumors correlated with high age and differentiated type tumors. BUBR1 aberrant expression, investigated using immunohistochemistry, was seen in 89 cases, and it correlated with malignant features such as deep invasion, and lymph node and liver metastases. DNA aneuploidy was significantly related to high BUBR1 expression (P = 0.0055), and a more significant relation was found between DNA aneuploidy and TP53mutation (P = 0.0032). Tumors with high BUBR1 expression showed poor prognosis. Conclusions: DNA aneuploidy is associated with the carcinogenesis and prognosis of gastric cancer. Therefore, there has been considerable interest in targeting cell cycle checkpoints, particularly in emerging and alternative anticancer strategies. The development of selection markers to aid in the selection of appropriate therapies for patients will be the primary focus of future research. TP53 mutation and BUBR1 expression may provide clinically useful diagnostic, therapeutic, and prognostic information.

2021 ◽  
Author(s):  
Yoshihiko Kakiuchi ◽  
Satoru Kikuchi ◽  
Shinji Kuroda ◽  
Masahiko Nishizaki ◽  
Shunsuke Kagawa ◽  
...  

Abstract Background: Remnant gastric cancer (RGC) has been increasing for various reasons such as longer life span, medical progress, and others. It generally has a poor prognosis, and its mechanism of occurrence is unknown. The purpose of this study was to evaluate the clinicopathological features of and clarify the prognostic factors of RGC.Methods: Between January 2002 and January 2017, 39 patients with RGC following distal gastrectomy underwent curative surgical resection at the Okayama University Hospital; their medical records and immunohistochemically stained extracted specimens were used for retrospective analysis. Results: On univariate analysis, initial gastric disease, pathological lymph node metastasis, and pathological stage were the significant factors associated with a poor overall survival (OS) (p=0.0139, 0.0061, and 0.0158, respectively). Multivariate analysis of these 3 factors showed that only initial gastric disease caused by malignant disease was an independent factor associated with a poor prognosis (p=0.0141, odds ratio [OR]:4.151, 95% confidence interval [CI]:1.333-12.93). In addition, the presence of a left gastric artery (LGA), and tumor-infiltrating CD8+ T cell expression were higher in the benign disease group than in the malignant group (p<0.0001 and p=0.0485, respectively).Conclusion: The lymph flow change caused by lymph node dissection for malignant disease in initial surgery might have an effect on the suppression of tumor immunity and the poor prognosis of RGC.


2017 ◽  
Vol 41 (6) ◽  
pp. 687-692 ◽  
Author(s):  
Xiang Fu ◽  
Wei Xie ◽  
Xiaoxue Song ◽  
Kun Wu ◽  
Linkang Xiao ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Jiafeng Ouyang ◽  
Zhi Long ◽  
Guoqing Li

Circular RNAs (circRNAs), as a recently established group of endogenous noncoding RNAs, have been involved in the occurrence and development of different malignancies. Gastric cancer (GC) remains a globally significant contributor to death in cancer patients due to insufficient early diagnosis, limited treatment measures, and poor prognosis. An increasing number of studies have found that many circRNAs are dysregulated in GC and are closely associated with its tumorigenesis and metastasis. Thus, circRNAs have the potential to serve as diagnostic and prognostic biomarkers and even therapeutic targets. This review comprehensively summarizes the most recent findings on how circRNAs influence GC progression and their clinical value. In addition, we present several methological deficiencies in the studies and provide some promising ideas for future research.


Oncology ◽  
2016 ◽  
Vol 91 (1) ◽  
pp. 31-40 ◽  
Author(s):  
Hajime Otsu ◽  
Makoto Iimori ◽  
Koji Ando ◽  
Hiroshi Saeki ◽  
Shinichi Aishima ◽  
...  

2011 ◽  
pp. 81-87
Author(s):  
Thi Thu Huong Hoang ◽  
Minh Vuong Nguyen

Objectives: Studying on the variation in CA 72-4 levels of the gastric cancer’s patients before and after 10 days and 30 days surgery treatment. Materials and methods: The studying group included 42 gastric cancer’s patients who were examinated and treated in cancerology service of Hue University Hospital and gastroenterology service of Hue Central Hospital. The control group included 30 healthy normal examinated at Hue University Hospital. The study groups were clinical, endoscopic anatopathologic examination diagnosed with gastric cancer and quantitative levels of CA 72-4 in three times points: before surgerying, after surgerying 10 days and 30 days postoperatively. Rerults: The concentration of CA 72-4 in gastric cancer’s patients was 10.06 ± 16.49 U/ml. Clearly higher than the control group 1.2 ± 0.4 U/ml(p <0.01). The rate increased levels of CA 72-4 in gastric cancer’s patients before surgerying was 27.5% and the control group was 0%. After 10 days of surgery, CA 72-4 level was 5.56 ± 8.55 U/ml; 82.5% of patients have reduced levels of CA 72-4 and 17.5% no changes; there are 0% increased cases. After 30 days of surgery, CA 72-4 level was 3.79 ± 6,52 U/ml. CA 72-4 level 10 days after surgering have decreased significantly compared to before surgery (p < 0.05) and 30 days after surgery have decreased significantly compared to after 10 days (p < 0.05). 30 days postoperatively, 90% patients had reduced levels of CA 72-4, 10% no changes, no patient had increased levels of CA 72-4 and no patient be relapsed after 30 days of treatment. Conclusions: CA 72-4 concentrations before surgerying increased 27.5%, after surgery 10 days and 30 days reduced step by step, no case have increased CA 72-4 levels, no case relapsed after 30 days.


2021 ◽  
pp. 1-10
Author(s):  
Zhongyin Yang ◽  
Chao Yan ◽  
Wentao Liu ◽  
Wei Xu ◽  
Chen Li ◽  
...  

BACKGROUND: Gastric cancer (GC) patients with peritoneal metastasis usually have extremely poor prognosis. Intraperitoneal infusion of paclitaxel (PTX) provides an effective treatment, but relapse and PTX-resistance are unavoidable disadvantages, and it is difficult to monitor the occurrence of PTX-resistance. OBJECTIVE: The aim of this study was to explore novel autoantibodies in the ascites of individuals with relapsed PTX-resistant GC with peritoneal metastasis. METHODS: Ascites samples were collected before PTX infusion and after the relapse in 3 GC patients. To determine the expression of significantly changed proteins, we performed autoantibody profiling with immunome protein microarrays and tandem mass tag (TMT) quantitative proteomics, and then, the overlapping proteins were selected. RESULTS: Thirty-eight autoantibodies that were differentially expressed between the ascites in the untreated group and relapsed PTX-resistant group were identified. For confirmation of the results, TMT quantitative proteomics was performed, and 842 dysregulated proteins were identified. Four proteins, TPM3, EFHD2, KRT19 and vimentin, overlapped between these two assays. CONCLUSIONS: Our results first revealed that TPM3, EFHD2, KRT19 and vimentin were novel autoantibodies in the ascites of relapsed PTX-resistant GC patients. These autoantibodies may be used as potential biomarkers to monitor the occurrence of PTX-resistance.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dejun Wu ◽  
Zhenhua Yin ◽  
Yisheng Ji ◽  
Lin Li ◽  
Yunxin Li ◽  
...  

AbstractLncRNAs play a pivotal role in tumorigenesis and development. However, the potential involvement of lncRNAs in colon adenocarcinoma (COAD) needs to be further explored. All the data used in this study were obtained from The Cancer Genome Atlas database, and all analyses were conducted using R software. Basing on the seven prognosis-related lncRNAs finally selected, we developed a prognosis-predicting model with powerful effectiveness (training cohort, 1 year: AUC = 0.70, 95% Cl = 0.57–0.78; 3 years: AUC = 0.71, 95% Cl = 0.6–0.8; 5 years: AUC = 0.76, 95% Cl = 0.66–0.87; validation cohort, 1 year: AUC = 0.70, 95% Cl = 0.58–0.8; 3 years: AUC = 0.73, 95% Cl = 0.63–0.82; 5 years: AUC = 0.68, 95% Cl = 0.5–0.85). The VEGF and Notch pathway were analyzed through GSEA analysis, and low immune and stromal scores were found in high-risk patients (immune score, cor =  − 0.15, P < 0.001; stromal score, cor =  − 0.18, P < 0.001) , which may partially explain the poor prognosis of patients in the high-risk group. We screened lncRNAs that are significantly associated with the survival of patients with COAD and possibly participate in autophagy regulation. This study may provide direction for future research.


2021 ◽  
Vol 20 ◽  
pp. 153303382110049
Author(s):  
Tao Ran ◽  
ZhiJi Chen ◽  
LiWen Zhao ◽  
Wei Ran ◽  
JinYu Fan ◽  
...  

Background and Objective: Gastric cancer (GC) is a common tumor malignancy with high incidence and poor prognosis. Laminin is an indispensable component of basement membrane and extracellular matrix, which is responsible for bridging the internal and external environment of cells and transmitting signals. This study mainly explored the association of the LAMB1 expression with clinicopathological characteristics and prognosis in gastric cancer. Methods: The expression data and clinical information of gastric cancer patients were downloaded from The Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG). And we analyzed the relationship between LAMB1 expression and clinical characteristics through R. CIBERSORTx was used to calculate the absolute score of immune cells in gastric tumor tissues. Then COX proportional hazard models and Kaplan-Meier curves were performed to evaluate the role of LAMB1 and its influence on prognosis in gastric cancer patients. Finally, GO and KEGG analysis were applied for LAMB1-related genes in gastric cancer, and PPI network was constructed in Cytoscape software. Results: In the TCGA cohort, patients with gastric cancer frequently generated LAMB1 gene copy number variation, but had little effect on mRNA expression. Both in the TCGA and ACRG cohorts, the mRNA expression of LAMB1 in gastric cancer tissues was higher than it in normal tissues. All patients were divided into high expression group and low expression group according to the median expression level of LAMB1. The elevated expression group obviously had more advanced cases and higher infiltration levels of M2 macrophages. COX proportional hazard models and Kaplan-Meier curves revealed that patients with enhanced expression of LAMB1 have a worse prognosis. GO/KEGG analysis showed that LAMB1-related genes were enriched in PI3K-Akt signaling pathway, focal adhesion, ECM-receptor interaction, etc. Conclusions: The high expression of LAMB1 in gastric cancer is related to the poor prognosis of patients, and it may be related to microenvironmental changes in tumors.


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