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DNA methylation. (A) CpG methylation mechanism is mediated by DNA methyltransferases and consists in the addition of a methyl group to the carbon in the 5th position of cytosines that precedes guanine nucleotides. (B) CpG islands are DNA sequences rich in CpG sites (>50% CpG sites within a 200bp sequence). Methylation of CpG islands inside a promoter region may control gene expression.
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... island methylation is an epigenetic mecha- nism of gene expression regulation, affecting all cellular pathways [59]. It consists of methyl groups attached to the 5′ position of cytosines, which are followed by a guanine nucleotide (CpG site) [60] (Figure 6). More than 50% of human genes contain CpG site in the pro- moter region and are known as CpG islands [62]. ...
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... As reported by other studies, we also observed a higher frequency of EBV-positive GC cases among male patients [40,41]. Although the results did not reach statistical significance in our study due to the sample size (p = 0.064), this could be a relevant factor if the sample size were increased. ...
The Epstein-Barr virus (EBV) has been associated with gastric cancer (GC), one of the deadliest malignancies in Chile and the world. Little is known about Chilean EBV strains. This study aims to investigate the frequency and genetic diversity of EBV in GC in patients in southern Chile. To evaluate the prevalence of EBV in GC patients from the Chilean population, we studied 54 GC samples using the gold standard detection method of EBV-encoded small RNA (EBER). The EBV-positive samples were subjected to amplification and sequencing of the Epstein-Barr virus nuclear protein 3A (EBNA3A) gene to evaluate the genetic diversity of EBV strains circulating in southern Chile. In total, 22.2% of the GC samples were EBV-positive and significantly associated with diffuse-type histology (p = 0.003). Phylogenetic analyses identified EBV-1 and EBV-2 in the GC samples, showing genetic diversity among Chilean isolates. This work provides important information for an epidemiological follow-up of the different EBV subtypes that may cause GC in southern Chile.
... The GS subtype consisted mainly of tumors classified as diffuse GC, with poorer survival compared to the Lauren gut type, and was associated with mutations in the CDH1 (cadherin-1) and RHOA (Ras homolog family member A) genes as well as with aneuploidy ( Figure 4). The immunogenic GC subtypes EBV and MSI are likely more prominent to the immune system due to the expression of more neoantigens and other foreign epitopes that stimulate a strong immune response that can be enhanced with current therapies, while the less immunogenic GC, CIN, and GS subtypes are more hidden, and lower antigen presentation provides a stronger defense system against host immune attack [16,72]. To improve the efficacy of GC immunotherapy, new criteria based on different The molecular, genetic, and immunological heterogeneity described by the TCGA emphasizes the need to stratify patients based on the likelihood of their response to various treatments, including immunotherapy. ...
... The GS subtype consisted mainly of tumors classified as diffuse GC, with poorer survival compared to the Lauren gut type, and was associated with mutations in the CDH1 (cadherin-1) and RHOA (Ras homolog family member A) genes as well as with aneuploidy ( Figure 4). The immunogenic GC subtypes EBV and MSI are likely more prominent to the immune system due to the expression of more neoantigens and other foreign epitopes that stimulate a strong immune response that can be enhanced with current therapies, while the less immunogenic GC, CIN, and GS subtypes are more hidden, and lower antigen presentation provides a stronger defense system against host immune attack [16,72]. To improve the efficacy of GC immunotherapy, new criteria based on different molecular and immunological subtypes are needed to predict potential response and prognosis [69]. ...
Gastric cancer remains one of the most commonly diagnosed cancers in the world, with a relatively high mortality rate. Due to the heterogeneous course of the disease, its diagnosis and treatment are limited and difficult, and it is associated with a reduced prognosis for patients. That is why it is so important to understand the mechanisms underlying the development and progression of this cancer, with particular emphasis on the role of risk factors. According to the literature data, risk factors include: changes in the composition of the stomach and intestinal microbiota (microbiological dysbiosis and the participation of Helicobacter pylori), improper diet, environmental and genetic factors, and disorders of the body’s immune homeostasis. Therefore, the aim of this review is to systematize the knowledge on the influence of human microbiota dysbiosis on the development and progression of gastric cancer, with particular emphasis on the role of the immune system in this process.
... 9,10 In addition, EBVaGC was characterized by predominance in males and a preferential location in the cardiac stomach. 10,11 Studies in East Asia reported an EBVaGC prevalence ranging from 6.1% in Northern China to 9.1% in Southern China. 12 In Japan and Korea, the prevalence is 6.6% 13 and 6.9%, 14 respectively. ...
... Previous studies reported that EBV-positive GCs are more common among males and younger patients and that these localize primarily to the cardia and body of the stomach. 10,11 In this study, three of four cases were male, two of four cases were located in the body, and one case was located in the cardia. Given the low number of EBVaGC cases, our data cannot draw conclusions on the prevalence of EBVaGC relative to patient gender and location of cancer. ...
The Epstein‐Barr virus (EBV) is one of the infectious agents found in stomach tissue. Recently, EBV associated gastric carcinoma (EBVaGC) was classified as a new subtype of gastric carcinoma. To date, there is a lack of knowledge about the distribution and prevalence of EBV infection in both the normal stomach and various gastric lesions, including EBVaGC, in the Thai population. In this study, we detected EBV in the normal stomach (NS; n=19), chronic gastritis (CG; n=36), intestinal metaplasia (IM; n=40), gastric dysplasia (GD; n=15), and gastric adenocarcinoma (GC; n=33) by polymerase chain reaction (PCR) amplification of the latent membrane protein (LMP1) gene of EBV. EBV‐PCR amplification was positive in 42.1%, 36.1%, 22.5%, 13.3%, and 33.3% of NS, CG, IM, GD, and GC, respectively. For further clarification in EBVaGC, we performed EBV‐encoded small RNA in situ hybridization (EBER‐ISH) in PCR positive cases of GD and GC. Four GC cases were EBER‐ISH positive (12.1%), while both GD cases were EBER‐ISH negative. In addition, we determined the distribution of the EBV strain (type A or B) based on EBNA3C sequence and EBV variants based on LMP1 variation (wild‐type and 30 bp‐deletion variants; wt‐LMP1 or del‐LMP1). The results showed that type A and wt‐LMP1 were the most prevalent in all lesions. In conclusion, EBV is common in both the normal stomach and gastric lesions and the frequency of EBVaGC was 12.1% in Thai patients.
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Les cancers de l’ovaire présentent un taux de survie à 5 ans inférieur à 40% et constituent la principale cause de décès par cancer gynécologique dans le monde. Ce sombre pronostic s’explique par un diagnostique tardif (du à un développement asymptomatique dans les premiers stades) et une résistance aux traitements existants et souligne la nécessité de développer de nouvelles approches thérapeutiques. La découverte ces dernières années, d’un nombre important de lncRNAs a permis d’ouvrir de nouvelles perspectives pour la recherche en oncologie. Peu d’études ont à ce jour exploré leur implication dans la chimiorésistance, a fortiori dans les cancers de l’ovaire. Parmi ces lncRNAs, ‘UCA1’ exerce de multiples fonctions oncogéniques par des mécanismes encore peu décrits. Son expression constitue un facteur de mauvais pronostique dans diverses tumeurs malignes dont les cancers de l’ovaire. Nous avons pu démontrer un rôle de ceRNA pour le miR-27a-5p, qui une fois libéré suite à l’inhibition d’UCA1, régule négativement UBE2N, une cible directe. UBE2N est un acteur connu des voies de réparation de l’ADN et de la régulation de la voie NF-kB, et son inhibition dans nos modèles entraîne une augmentation de l’expression de BIM et perturbe les mécanismes de réparation de l’ADN, sensibilisant des cellules cancéreuses ovariennes à l’action des sels de platine et des PARPi. L’inhibition d’UBE2N sensibilise également aux sels de platine plusieurs cultures organoïdes tridimensionnelles dérivées de patientes, et pourrait ainsi constituer une stratégie thérapeutique innovante pour lutter contre la chimiorésistance dans le cancer de l'ovaire.
Emerging evidence suggests that chronic inflammation caused by pathogen infection is connected to the development of various types of cancer. It is estimated that up to 20% of all cancer deaths is linked to infections and inflammation. In gastric cancer, such triggers can be infection of the gastric epithelium by either Helicobacter pylori (H. pylori), a bacterium present in half of the world population; or by Epstein-Barr virus (EBV), a double-stranded DNA virus which has recently been associated with gastric cancer. Both agents can establish lifelong inflammation by evolving to escape immune surveillance and, under certain conditions, contribute to the development of gastric cancer. Non-coding RNAs, mainly microRNAs (miRNAs), influence the host innate and adaptive immune responses, though long non-coding RNAs and viral miRNAs also alter these processes. Reports suggest that chronic infection results in altered expression of host miRNAs. In turn, dysregulated miRNAs modulate the host inflammatory immune response, favoring bacterial survival and persistence within the gastric mucosa. Given the established roles of miRNAs in tumorigenesis and innate immunity, they may serve as an important link between H. pylori- and EBV-associated inflammation and carcinogenesis. Example of this is up-regulation of miR-155 in H. pylori and EBV infection. The tumor environment contains a variety of cells that need to communicate with each other. Extracellular vesicles, especially exosomes, allow these cells to deliver certain type of information to other cells promoting cancer growth and metastasis. Exosomes have been shown to deliver not only various types of genetic information, mainly miRNAs, but also cytotoxin-associated gene A (CagA), a major H. pylori virulence factor. In addition, a growing body of evidence demonstrates that exosomes contain genetic material of viruses and viral miRNAs and proteins such as EBV latent membrane protein 1 (LMP1) which are delivered into recipient cells. In this review, we focus on the dysregulated H. pylori- and EBV-associated miRNAs while trying to unveil possible causal mechanisms. Moreover, we discuss the role of exosomes as vehicles for miRNA delivery in H. pylori- and EBV-related carcinogenesis.
