Abstract 5680: Hypoxia-responsive and HIF1α-regulated AAA+ ATPase ATAD2 shows high oncogenic potential in stomach cancer
0
Citation
0
Reference
10
Related Paper
Abstract:
Abstract The burden of stomach cancer incidence and death is a global challenge. Treating stomach cancer remains immensely difficult due to the lack of available markers to detect the disease at the early stages. Therefore, there is an immense demand for finding out an early detection biomarker for stomach cancer. Recently, ATAD2 is found to be overexpressed in stomach cancer with high prognostic significance and recognised as a promising biomarker for stomach cancer. ATAD2 is a unique cancer/testis antigen (CTA) that belongs to both AAA+ ATPase and bromodomain family proteins. However, nothing much is known about the mechanism of ATAD2-mediated stomach carcinogenesis. Using bioinformatics analyses as well as studies with stomach cancer cells and stomach biopsy tissue samples, we address the regulation and function of ATAD2 expression in stomach cancer. We show that ATAD2 is overexpressed in the most common intestinal type of stomach adenocarcinoma, and enhanced expression of ATAD2 is observed in all stages and grades of stomach cancer. Our immunofluorescence microscopy study with stomach biopsy tissues confirms the high expression of ATAD2 both in stomach adenocarcinoma and metastatic stomach tissue samples. Survival analysis indicates that upregulated ATAD2 expression drastically affects the survival of stomach cancer patients. Since H. pylori infection, and hypoxia are the major contributing factors for stomach carcinogenesis; we further study their role in ATAD2-mediated stomach malignancy. An enhanced expression of ATAD2 is observed in H. pylori-infected stomach cancer cells. We identify ATAD2 as a hypoxia-responsive and HIF1α-regulated gene and elucidate that upregulated expression of ATAD2 enhances proliferation and migration of hypoxic stomach cancer cells. We further recognize the protein-protein interaction (PPI) network of ATAD2 with the top-ranked partners like ESR1 (or ERα), NCOA3 (or ACTR/SRC3/AIB1), SUMO2, HDA11 (HDAC11), SPTN2 (SPTBN2), and MYC. Among them, ESR1, MYC, NCOA3, and HDA11 are oncoproteins. Most strikingly, we report the participation of two druggable targets of ATAD2, i.e., AAA+ ATPase and bromodomain in the ATAD2-PPI network; ESR1, SUMO2, SPTN2, and MYC show a preference for bromodomain, whereas NCOA3 and HDA11 prefer ATPase domain of ATAD2. The importance of such findings in terms of targeting bromodomain-PPI and/or ATPase-PPI interfaces to curtail stomach cancer is elucidated. Citation Format: Anasuya Roychowdhury, Aditi Nayak, Sugandh Kumar, Anshuman Dixit, Asima Bhattacharyya. Hypoxia-responsive and HIF1α-regulated AAA+ ATPase ATAD2 shows high oncogenic potential in stomach cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5680.Keywords:
Stomach cancer
Objective To outline the significances of CD44v6 and MMP-9 expressed in stomach cancer and the effect of them on metastasis and invasiveness of stomach cancer.Methods An immunohistochemical S-P method was used to detect the expression of CD44v6 and MMP-9 in 128 samples of stomach cancer after operation. Results In 128 cases of stomach tissues,of 75 cases(58.59%) expressed CD44v6 positively and of 82 cases(64.06%) expressed MMP-9 positively,both of them correlated to the stomach growth ways,invasive depth,with or without lymph node metastasis,TNM staging(P0.05 or 0.01);the expression of MMP-9 in diffuse type stomach cancer were higher than that in intestinal-type stomach cancer(P0.01).The five-year survival rate in patients with stomach cancer with expression of MMP-9 was lower than those without expression of MMP-9(P0.05).Both of CD44v6 and MMP-9 in patients with stomach cancer had positive correlation to the cancer progression,the incidence of lymph node metastasis was higher in patients with both higher expression of CD44v6 and MMP-9 than those with only one of the positive expression or without both of the expression(P0.05 or 0.01);of the cases that expressed both CD44v6 and MMP-9 were found with more serosal invasiveness than those without both of the expression(P0.01).Conclusion CD44v6 and MMP-9 can promote the stomach cancer growth,invasiveness and metastasis of the stomach cancer,they can be used as an important marker for predicting the stomach cancer biological behavior and prognosis.
Stomach cancer
Cite
Citations (0)
The present study was planned to investigate miR-143 expression during stomach cancer. The study explored the relationship between miR-143 expression and clinicopathological characteristics including proliferation, migration and apoptosis of stomach cancer cells. Sixty-three samples from each of stomach cancer tissue and surrounding tissue were obtained. Total RNA was extracted. The expression levels of miR-143 from stomach cancer tissue as well as from surrounding tissue were measured by semi-quantitative PCR. The effects of miR-143 overexpression on the migration of stomach cancer cells were examined by Transwell assay. The effects of miR-143 overexpression on the apoptosis of stomach cancer cells were examined by flow cytometer. The expression level of miR-143 was significantly decreased in stomach cancer tissues in comparison to surrounding tissues (P<0.01). Moreover, the expression of miR-143 related well with the tumor size, TNM stage, lymphatic metastasis and relapse (P<0.01). On the other hand, stomach cancer cell line with overexpression of miR-143, showed significant decline in proliferation rate and migration rate comparison to control cells (P<0.01). However, it showed significant higher in apoptosis rate (P<0.01). The present study concluded that expression of miR-143 is low during stomach cancer. Further, higher expression levels of miR-143 have the ability to decline proliferation and migration of stomach cancer cells. In this manner, the expression level of miR-143 could be used as an important factor to determine the severity of stomach cancer.
Stomach cancer
Cite
Citations (2)
Stomach cancer
Cite
Citations (0)
Stomach cancer
Cite
Citations (10)
Abstract The burden of stomach cancer incidence and death is a global challenge. Treating stomach cancer remains immensely difficult due to the lack of available markers to detect the disease at the early stages. Therefore, there is an immense demand for finding out an early detection biomarker for stomach cancer. Recently, ATAD2 is found to be overexpressed in stomach cancer with high prognostic significance and recognised as a promising biomarker for stomach cancer. ATAD2 is a unique cancer/testis antigen (CTA) that belongs to both AAA+ ATPase and bromodomain family proteins. However, nothing much is known about the mechanism of ATAD2-mediated stomach carcinogenesis. Using bioinformatics analyses as well as studies with stomach cancer cells and stomach biopsy tissue samples, we address the regulation and function of ATAD2 expression in stomach cancer. We show that ATAD2 is overexpressed in the most common intestinal type of stomach adenocarcinoma, and enhanced expression of ATAD2 is observed in all stages and grades of stomach cancer. Our immunofluorescence microscopy study with stomach biopsy tissues confirms the high expression of ATAD2 both in stomach adenocarcinoma and metastatic stomach tissue samples. Survival analysis indicates that upregulated ATAD2 expression drastically affects the survival of stomach cancer patients. Since H. pylori infection, and hypoxia are the major contributing factors for stomach carcinogenesis; we further study their role in ATAD2-mediated stomach malignancy. An enhanced expression of ATAD2 is observed in H. pylori-infected stomach cancer cells. We identify ATAD2 as a hypoxia-responsive and HIF1α-regulated gene and elucidate that upregulated expression of ATAD2 enhances proliferation and migration of hypoxic stomach cancer cells. We further recognize the protein-protein interaction (PPI) network of ATAD2 with the top-ranked partners like ESR1 (or ERα), NCOA3 (or ACTR/SRC3/AIB1), SUMO2, HDA11 (HDAC11), SPTN2 (SPTBN2), and MYC. Among them, ESR1, MYC, NCOA3, and HDA11 are oncoproteins. Most strikingly, we report the participation of two druggable targets of ATAD2, i.e., AAA+ ATPase and bromodomain in the ATAD2-PPI network; ESR1, SUMO2, SPTN2, and MYC show a preference for bromodomain, whereas NCOA3 and HDA11 prefer ATPase domain of ATAD2. The importance of such findings in terms of targeting bromodomain-PPI and/or ATPase-PPI interfaces to curtail stomach cancer is elucidated. Citation Format: Anasuya Roychowdhury, Aditi Nayak, Sugandh Kumar, Anshuman Dixit, Asima Bhattacharyya. Hypoxia-responsive and HIF1α-regulated AAA+ ATPase ATAD2 shows high oncogenic potential in stomach cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5680.
Stomach cancer
Cite
Citations (0)
Stomach cancer is believed to be one of the most common cancers that lead to death. In Iraq, stomach cancer occupies the seventh place of cancer occurrence in both sexes and is counted as one of the ten most common cancers. The current study is designed to explore the link between Helicobacter pylori (H.pylori) infection and the development of incidences of stomach cancer. In addition, related age and gender were also studied. Histological examinations of stomach biopsies were performed in suspected people to evaluate stomach cancer occurrences. Of the 40 patients with stomach cancer, the infection of H. pylori was emphasized in 34 (66.66%) with serum IgG/IgM, which reflected a significant frequency for infection of H. pylori in stomach cancer patients. The study also showed that males with H. pylori infection record a higher percentage than female patients with stomach cancer. Moreover, the results revealed that age is also connected to H. pylori infection. Based on the above findings, monitoring infected people with H. pylori might be an excellent strategy to control stomach cancer occurrences. Keywords: Stomach cancer, Infectious diseases, IgG, IgM, H. pylori.
Stomach cancer
Cite
Citations (0)
Objective:To detect methylation in p16 gene in whole blood and tissue of stomach cancer, and to explore its significance for early diagnosis in stomach cancer.Method:44 tissue samples and their corresponding whole blood samples from patients with stomach cancer, 20 tissue samples with gastric ulcer were collected for methylation measurement by PCR technique.Result:Methylated p16 gene was found in 38.6%(17/44)of stomach cancer and in (88.2%)(15/17) whole blood samples, no methylated p16 gene was found in gastric ulcer. Methylated p16 gene promoter in whole blood strongly correlated with tissue of stomach cancer.Conclusion:The measurement of methylated p16 gene should be helpful to early diagnosis in stomach cancer.
Stomach cancer
Human stomach
Cite
Citations (3)
A comparative evaluation of the results of mass gastro-fluorographic screenings with the aid of special-purpose gastrofluorographs and pulmonary fluorographs adapted for stomach examination in lateral position. Although stomach radiograms obtained by use of pulmonary fluorography installations provide less information, the latter prove to be a good substitute in carrying out mass screenings for stomach tumors, when special-purpose gastrofluorographs are not available. Stomach cancer incidence in out-patients with stomach diseases is 7 times that in subjects who have no complaints, and 2-4 times in patients with stomach disturbances unregistered at dispensary clinics.
Stomach cancer
Dispensary
Cite
Citations (0)
Experiments were conducted in order to determine magnesium concentrations in stomach cancer tissue. As a control, non-cancerous stomach tissue of the same patients was used. Mg concentration in blood serum was also tested in all patients undergoing surgical operation. It has been determined that Mg concentration was higher in cancerous stomach tissue than in control tissue. Average Mg concentration in the blood serum of patients with stomach cancer fluctuates near the lower limit of normal. An analysis of the relationship between Mg concentration and the degree of clinical advancement of cancer has shown that Mg concentration in cancerous stomach tissue increases with the clinical stage. The results obtained were statistically significant. They show that there is a relationship between Mg concentration and the development of stomach cancer.
Stomach cancer
Human stomach
Cite
Citations (7)