scholarly journals Clinicopathological Features' Correlation and Genes’ Expression of NEAT1, lincRNA-ROR and Oct4 in Iranian Patients with Gastric Cancer

Author(s):  
Vahid Chaleshi ◽  
Mahyar Nourian ◽  
Naghmeh Zamani ◽  
Narjes Mehrvar ◽  
Shahrokh Iravani ◽  
...  

Abstract Purpose Long non-coding RNAs (LncRNAs) play a critical role in the initiation and development of Gastric Cancer(GC). The aim of this study was to consider the expression of NEAT1, lincRNA-ROR and Oct4 and finally evaluate the correlation between their expression and clinical characteristics in Iranian patients with GC. Methods This cross-sectional study was performed on 41 gastric tumor tissue samples with matched normal adjacent tumor tissues. The RNA level of lncRNA NEAT1 and lincRNA ROR and Oct4 genes were assessed using the quantitative Real-time polymerase chain reaction. B2M was used as an internal control. Also, the relative expression of lncRNA NEAT1 and lincRNA ROR compared Oct4 in GC tissues was evaluated. The 2 −ΔΔCq method was used to determine the expression fold changes. Results A significant association was observed between the levels of lincRNA ROR and Oct4 genes in gastric tumor tissues comparing normal adjacent tissues (Mean = 1.558, p= 0.014), (Mean = 3.337, p< 0.001) and (Mean= 4.385, p<0.001), respectively. In addition, clinicopathological data comparing with lncRNAs and Oct4 mRNA expression levels in gastric cancer tissues showed no significant association. Here, we found that significant association between the levels of lincRNA ROR expression comparing oct4 mRNA level in gastric cancer tissues (R=0.417; P=0.024). Conclusion Our results Showed that lincRNA ROR and Oct4 have a significant association in gastric cancer. Also, our results indicate the first suggestion that lincRNA ROR expression correlated with oct4 mRNA level in gastric cancer tissues.

2020 ◽  
Vol 4 (1) ◽  
pp. 01-03
Author(s):  
Osman Demirhan ◽  
Deniz Taştemir Korkmaz ◽  
Nesrin Çetinel

Breast cancer (BC) is the most prevalent malignant disease in females worldwide. Genomic instability in tumor tissue has been associated with tumor progression. These genetic changes may take a variety of forms, including numerical and structural chromosomal abnormalities (CAs), epigenetic changes, and gene expression alterations. Many tumor tissues are made up of genetically different cell populations, and the study of the causes and consequences of this heterogeneity play a central role in cancer research. In this study, CAs in blood and cancer tissues of patients with sporadic BC were examined. Our findings shows that the increase in numerical sex aneuploidy in BC tissues is significantly higher than in blood tissue. These aneuploidy increases in cancer tissues seem to be compatible with the development and increase of cancer, and can play a role in the pathogenesis of cancers. These changes are consistent with early and long-standing exposure to carcinogens, especially estrogens. These findings should clarify our understanding of breast carcinogenesis in breast tissues and promote development of improved methods for risk assessment and BC prevention in women.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15089-e15089
Author(s):  
Jedi Maher ◽  
Graeme P Young ◽  
Susanne Kartin Pedersen ◽  
Erin L. Symonds

e15089 Background: BCAT1 and IKZF1are methylated with high frequency in colorectal cancer (CRC). This study aimed to investigate the level of methylation in these two genes in tissue samples from CRC patients who had undergone radiotherapy. Methods: Tumor and adjacent non-tumor tissue was collected from 50 CRC patients, including 14 subjected to radiotherapy prior to surgical resection. DNA was extracted, bisulfite converted and the levels of methylated BCAT1 and IKZF1 DNA were expressed as the percentage of 5ng tissue DNA (normalized to ACTB levels). Results: In the 36 CRC patients who did not receive radiotherapy prior to resection, tumor tissues had high levels of methylated BCAT1 and IKZF1 compared with adjacent non-tumor tissues (p < 0.001, Table). The CRC tissues from the 14 patients who received radiotherapy pre-surgery had significantly lower levels of methylation compared to the levels in tumors from non-treated patients (p<0.01, Table). Radiotherapy did not appear to affect the methylated BCAT1/IKZF1DNA levels in adjacent non-cancer tissues (p > 0.05, Table). In this limited dataset, a correlation was observed with %methylation and response to radiotherapy measured based on tumor size relative to original size, with the lowest methylation in the tumors associated with the greatest downsizing. Conclusions: The high levels of methylated BCAT1 and IKZF1 in CRC tissue and the low levels in the surrounding non-cancer tissue suggest that the markers are tumor specific with no obvious field effect. In contrast, in the samples obtained from patients treated with radiotherapy prior to resection, the methylation levels in CRC tissues were similar to the levels measured in the adjacent non-tumor tissues. Further studies are necessary to determine the reason for this and whether it has implications for monitoring response to therapy based on blood levels of methylated BCAT1 and IKZF1. [Table: see text]


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17001-e17001
Author(s):  
Galina Andreevna Nerodo ◽  
Oleg Ivanovich Kit ◽  
Tatiana Zykova ◽  
Victoria A. Ivanova ◽  
Vera P. Nikitina ◽  
...  

e17001 Background: The purpose of the study was to determine the rate of various HPV genotypes detection in tissues of tumors of the female reproductive organs. Methods: FFPE and frozen tissue samples of cervical cancer (n=126), vulvar cancer (n=113) and uterine cancer (n=29) were studied. DNAs of HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 were determined by the Real-Time PCR. Results: HPV DNAs were found in 94.4% of samples of cervical cancer tissue, 65.5% - uterine cancer tissue and 28.3% - vulvar cancer tissue. HPV 16 and 18 were the most frequent (78.8%). HPV 16 in cervical cancer was detected in 60.9%, vulvar cancer – 59.0% and uterine cancer – 54.5%. On the contrary, HPV 18 was more frequent in uterine cancer (40.9%) and less frequent in cervical cancer (18.4%) and vulvar cancer (2.7%). Besides HPV 16 and 18, genotypes 31, 33, 35, 39, 45, 51, 52, 56 and 59 were found in tumor tissues as well (21.2% in total). HPV 35, 52 and 56 were the most frequently detected. Cervical cancer tissues showed the greatest genetic diversity of HPV and uterine cancer tissues – the lesser one (HPV 35 only, besides HPV 16 and 18). Combination of several HPV types was also more frequent in cervical cancer (37.0% of positive samples); in vulvar cancer – 18.8% and in uterine cancer – 15.8%. Conclusions: The results confirm HPV significance in carcinogenesis of cervical cancer, vulvar cancer and probably uterine cancer and show genetic diversity of HPV in different localizations of tumors of the female reproductive system.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1021-A1021
Author(s):  
Junichi Okada ◽  
Eijiro Yamada ◽  
Tsugumichi Saito ◽  
Yasuyo Nakajima ◽  
Atsushi Ozawa ◽  
...  

Abstract Nucleobindin-2 (NUCB2) is a 396-amino acid protein, cleaved into the N-terminal nesfatin-11-82, nesfatin-285-163 and the C-terminal nesfatin-3166-396. NUCB2 contains a signal peptide, a leucine zipper structure, two Ca2+ binding EF-hand domains, and has a wide variety of basic cellular functions. NUCB2 is also a precursor protein of nesfatin-1, which was originally identified in hypothalamic nuclei, and which is a regulatory factor involved in the central control of food intake and energy balance. There are several reports indicating that NUCB2 is also expressed in various human peripheral tissues. Moreover, recent studies have reported that high levels of NUCB2 mRNA and protein are a potent prognostic factor for prostate cancer, endometrial carcinoma, and breast cancer. NUCB2 was also identified as a potential tumor antigen eliciting autoantibody responses in 5.4% of gastric cancer patients but not in the healthy individuals. However, theclinicopathological significance of NUCB2 expression in gastric cancer has still not been elucidated. Therefore, we examined NUCB2 expression in a large number of gastric cancer patients, using immunohistochemistry, to explore its clinicopathological significance. To explore this, we aimed to investigate the NUCB2 expression in gastric cancer tissues and adjacent non-tumor tissues and its potential relevance to clinicopathological factors and prognosis using immunohistochemistry analysis. In our study, NUCB2 level in gastric cancer tissues was higher than in non-tumor tissues. A high expression of NUCB2 is significantly associated with tumor depth, lymph node metastasis, lymphatic invasion, venous invasion and clinical stage. Furthermore, the expression level of NUCB2 protein was independent predictor of progression-free survival. In summary, NUCB2 might play a crucial role in gastric cancer development and could serve as an independent predictor of prognosis of gastric cancer patients.


2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Shaian Tavakolian ◽  
Hossein Goudarzi ◽  
Ebrahim Faghihloo

Abstract Objective Breast cancer is one of the most common health problems. It has been suggested that several risk factors, either considered as external or internal, play a critical role in the pathogenesis of breast cancer, which among them, HERV-k, has the most fundamental role. In the present study, we aimed to evaluate the role of HERV-k env, gag, rec, np9 expressions in breast cancer progression. Materials and methods We collected 40 breast cancer tissues and their normal adjacent ones. After extracting the RNA of breast samples, we evaluated the expression of HERV-k env, gag, rec, np9 by using Quantitative real-time PCR (qRT-PCR). Results The resulting data revealed that while there was a meaningful increase in the expression level of HERV-k env, gag and np9 in breast cancer tissues (P ≤ 0.01, 0.05, 0.05, respectively), we failed to find any significant elevation in the expression level of rec mRNA level. Conclusion The results of our study suggested that there is a plausible correlation between the mRNA expression level of HERV-K env, gag and np9 and the progression of breast cancer, proposing these markers as promising biomarkers to diagnose breast cancer.


Gut ◽  
2019 ◽  
Vol 68 (10) ◽  
pp. 1764-1773 ◽  
Author(s):  
Chao Lin ◽  
Hongyong He ◽  
Hao Liu ◽  
Ruochen Li ◽  
Yifan Chen ◽  
...  

ObjectiveOur previous studies have identified CXCL8 as the crucial chemokine responsible for gastric cancer metastasis mediated by loss of RACK1. However, the regulatory effect of CXCL8 on immune surveillance in gastric cancer remains obscure.DesignFlow cytometry analyses were performed to examine major source of CXCL8 and phenotypes of immune cells in fresh tumour tissues from 76 patients with gastric cancer. Real-time PCR was performed to analyse CXCL8 mRNA level in gastric cancer tissues. For immunohistochemical analyses, a total of 420 patients with gastric cancer undergoing curative resection were enrolled. In vitro culture of fresh tumour tissue was performed to evaluate the potential therapeutic effect of blocking CXCL8 pathway in gastric cancer.ResultsIncreased level of CXCL8 indicates poor clinical outcome and tumour progression in patients with gastric cancer. In gastric cancer tissues, CXCL8 is predominantly secreted by macrophages and colony stimulating factor 2 (CSF-2) facilitates macrophage-derived CXCL8 secretion. High level of CXCL8 is associated with decreased CD8+ T cells infiltration and Ki67+ CD8+ T cells proportion. Moreover, CXCL8 also inhibits CD8+ T cells function by inducing the expression of PD-L1 on macrophages. Finally, we show that a small-molecule CXCR2 inhibitor, reparixin, drives the decreased programmed death-ligand 1 (PD-L1+) macrophages and promotes antitumour immunity. Accordingly, high levels of CXCL8+ macrophages are positively correlated with poor prognosis in patients with gastric cancer.ConclusionsCXCL8 is predominantly secreted by macrophages and contributes to the immunosuppressive microenvironment by inducing PD-L1+ macrophages in gastric cancer. CXCL8 inhibitors may drive antitumour response, providing potential therapeutic effects for patients with gastric cancer.


2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 34-34
Author(s):  
Zheng Chen ◽  
Shoumin Zhu ◽  
Jun Hong ◽  
Abbes Belkhiri ◽  
Wael El-Rifai

34 Background: Gastric cancer is the second most frequent cause of cancer-related death worldwide. We have previously shown that Dopamine and cAMP regulated phosphoprotein MW 32 kDa (DARPP-32) and its truncated form (t-DARPP) are overexpressed in two-thirds of gastric adenocarcinomas. Angiopoietin 2 (ANGPT2) -TIE2 signaling is a secreted protein that acts as a key regulator of adult vascular homeostasis and blood vessel formation. Methods: The expression of DARPP-32 in the multi-step carcinogenesis cascade was examined using IHC analysis on 533 samples. ANGPT2 mRNA level was detected by real-time quantitative polymerase chain reaction (PCR) in 30 gastric cancer tissue samples and 30 normal gastric tissues. DARPP-32 and t-DARPP were over expressed using stable and transient expression in AGS and MKN-28 gastric cancer cell lines, lacking endogenous DARPP-32 to investigate the induction of ANGPT2 by DARPP-32 and t-DARPP. Results: We found that ANGPT2 was higher expressed in cancer samples than normal tissues from RT-PCR. We also found gastric cancer tissue samples expressed higher DARPP-32 and t-DARPP mRNA than normal gastric tissues. Over expression of DARPP-32 and t-DARPP led to a significant increase of the mRNA and protein levels of ANGPT2 as compared to empty vector control. Consistent with these findings, the condition media from DARPP-32 and t-DARRP expressing cells showed high levels of secreted ANGPT-2. TNF-α treatment induced the levels of ANGPT2 further in DARPP-32 and t-DARPP expressing cells as compared to control. Of note, this increase in NF-κB activity was significantly higher in DARPP-32 and t-DARPP expressing cells as compared to control. To confirm the angiogenic potential, we used condition media from DARPP-32 and t-DARPP expressing AGS cells and demonstrated its ability to stimulate tube formation on human umbilical vein endothelial cells (HUVEC) models than the condition medium from control cells. Conclusions: Our results suggest that DARPP-32 and t-DARPP over expression may participate in the angiogenesis of gastric cancer. The in vitro studies indicate that DARPP-32 and t-DARPP play a role in up regulation of ANGPT2 in gastric cancer cells by enhancing the TNF-α induced activation of NF-κB signaling pathway.


2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Gen Chen ◽  
Zhangshuo Yang ◽  
Maohui Feng ◽  
Zhiliang Wang

Abstract Background: Gastric cancer (GC) is the one of most common malignancies and its mechanism of metastasis remains unclear. The study was designed to investigate the effects of microRNA-217 on epithelial-to-mesenchymal transition. Methods: The expression levels of miR-217 in GC were assayed by real-time qPCR. Metastasis and invasion of cancer cell were assayed by transwell chamber. Double luciferase reporter gene was used to verify the target regulatory relationship between microRNA-217 and tyrosine–protein phosphatase non-receptor type 14 (PTPN14) on gastric cell lines. Epithelial-to-mesenchymal transition (EMT) markers were assayed by Western blot. Results: We found that miR-217 had a low level expression in gastric tumor tissues of 40 patients with GC, and a lower expression in the gastric tumor tissues of the patients with GC metastasis. Moreover, miR-217 markedly suppressed the metastasis and invasion of gastric cancer cell line in vitro. Furthermore, miR-217 inhibited the expression of PTPN14 by directly targeting its 3′UTR. Moreover, the down-regulation of PTPN14 reduced the metastasis and invasion, whereas up-regulation of PTPN14 led to the enhanced metastases and invasion of gastric cells. miR-217 induced the down-regulation of PTPN14 and inhibited the EMT in gastric cancer cells. Conclusion: miR-217 inhibited the EMT through directly targeting to the 3′UTR of PTPN14.


Author(s):  
Shun-tan Huang ◽  
Ze-zhen Liu ◽  
Fu-Neng Jiang ◽  
Hui-chan He ◽  
Wei-De Zhong

Abstract Objective: To compare the expression levels of Defective In Cullin Neddylation 1 Domain Containing 1 oncogene in prostate cancer tissues and normal prostate tissues, to explored its effect on cancerous  cells, and to investigate its underlying mechanisms on such cells in vitro. Methods: The cross-sectional study was conducted at Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics from Jan 03,2017 to Nov 05,2018, and comprised prostate tissue samples on which immunohistochemistry was used to detect the expression of Defective In Cullin Neddylation 1 Domain Containing 1 oncogene. Short hairpin ribonucleic acid expression plasmid targeting the oncogene was constructed and transferred into prostate cance cell line DU145. The roles of the oncogene in prostate cancer progression were confirmed in vitro. The expression of vimentin and epithelial cadherin influenced by the oncogene were detected using Western blot. Data was analysed using SPSS 24. Results: Of the 80 samples, 3(3.75%) were normal prostate tissues, 7(8.75%) adjacent normal prostate tissues, 20(25%) hyperplasia, and 50(62.5%) prostate cancer tissues. Defective In Cullin Neddylation 1 Domain Containing 1 oncogene expression in prostate cancerous tissues was significantly associated with high Gleason score (p<0.001), metastasis (p<0.05) and pathological stage (p<0.001). The oncogene was found to be an independent prognostic factor for disease-free survival of prostate cancer patients (p=0.0108). In vitro analysis confirmed the tumour promotive role of the oncogene through cell proliferation, invasion and migration assays. Continuous...


2021 ◽  
Author(s):  
Adriano Costa ◽  
Fernando Santa-Cruz ◽  
Raphael Araújo ◽  
Glauber Leitão ◽  
José-Luiz Figueiredo ◽  
...  

Abstract Background: recent experimental studies have shown a potential link between cathepsin S (CTTS) and gastric cancer progression. Herein, we aimed to evaluate the expression of CTTS in gastric adenocarcinoma.Methods: Cross-sectional study that included two groups, gastric adenocarcinoma (n=42) and gastritis (n=50). The gastritis group was then subdivided into H. pylori positive (n=25) x negative (n=25). Gastric tissue samples were analyzed in order to determine the CTTS expression through immunohistochemistry. Results: In patients with gastritis, the age ranged from 18 to 78 years. Among them, 34% were male, and 66% were female. In patients with gastric cancer, the age ranged from 37 to 85 years. Among them, 50% were male, and 50% were female. When comparing the expression of CTTS between the two groups, only 16% of the gastritis samples had an expression higher than 25%. On the other hand, among patients with gastric adenocarcinoma, 19% had expression between 25-50%, 14.3% between 51-75%, and 26.2% had expressions higher than 75% (p < 0.001). CTTS expression was significantly higher in patients with positive test for H. pylori: 87.5% x 38.5% (p<0.001). There was no statistically significant association between the positivity of CTTS and the clinical-pathological variables, including tumor staging, histological type, angiolymphatic invasion, recurrence, current status and death.Conclusion: CTTS has a higher expression in samples of gastric adenocarcinoma. Patients with gastritis by H. pylori also show a higher expression of CTTS compared with patients with negative results for this bacterium.


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