Downregulated Expression of E-cadherin and TP53 in Patients with Gastric Diseases: the Involvement of H. pylori Infection and Its Virulence Markers

Ferraz, Mariane Avante; Zabaglia, Luanna Munhoz; Pereira, Weendelly Nayara; Orcini, Wilson Aparecido; Lábio, Roger Willian de; Neto, Agostinho Caleman; Wisnieski, Fernanda; Calcagno, Danielle Queiroz; Santos, Leonardo Caires; Assumpção, Paulo Pimentel de; Burbano, Rommel Rodrı́guez; Artigiani, Ricardo; Smith, Marı́lia de Arruda Cardoso; Payão, Spencer Luíz Marques; Rasmussen, Lucas Trevizani

doi:10.1007/s12029-015-9782-4

Cited by 6 publications

(4 citation statements)

References 36 publications

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“…These results support previous studies 21, 28-31 , which demonstrate the up-regulation of many of these miRNAs in GC. These miRNAs regulate 18 driver genes (tumor suppressor genes; Table S4A), including APC 60 , RUNX1 61 , EP300 62-63 , KLF4 64-65 , PTEN 66-67 , TP53 68 , RB1 69 , SMAD2 70-71 and SMAD4 72-73 , which have already been reported to be down-regulated in GC. Studies has shown that hsa-miR-10a , -miR-21 , -miR-135b , -miR-148a , -miR-150 , -miR-215 and -miR-483 regulate important processes for the establishment and progression of gastric tumors, such as cell cycle progression, migration, proliferation, invasion, apoptosis and metastasis 56, 61, 74-81 .…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Field Cancerization in Gastric Cancer: microRNAs as Promising Biomarkers

et al. 2019

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Background: The biological role of microRNAs (miRNAs) in field cancerization is unknown. To investigate the involvement of miRNAs in gastric field cancerization, we evaluated the expression profile of ten miRNAs and their diagnostic value. Methods: We used three groups of FFPE gastric samples: non-cancer (NC), cancer adjacent (ADJ) and gastric cancer (GC). The expression profiles of hsa-miR-10a , -miR-21, -miR-29c, -miR-135b , -miR-148a , -miR-150 , -miR-204 , -miR-215 , -miR-483 and -miR-664a were investigated using qRT-PCR. The results obtained by qRT-PCR were validated in Small RNA-Seq data from the TCGA database. The search for target genes of the studied miRNAs was performed in the miRTarBase public database and miRTargetLink tool, using experimentally validated interactions. In addition, we also performed the functional analysis of these genes using enrichment in KEGG pathways. The potential as biomarker was evaluated using a receiver operating characteristic (ROC) curve and the derived area under the curve (AUC>0.85) analysis. Results: The miRNAs hsa-miR-10a , -miR-21 , -miR-135b , hsa-miR-148a , -miR-150 , -miR-215 , -miR-204 , -miR-483 and -miR-664a were up-regulated in ADJ and GC compared to NC ( P <0.03); and hsa-miR-21 and -miR-135b were up-regulated in GC compared to ADJ ( P <0.01). Hsa-miR-148a , -miR-150 , -miR-215 , -miR-483 and -miR-664a were not differentially expressed between GC and ADJ, suggesting that both share similar changes ( P >0.1). The TS-miR hsa-miR-29c was up-regulated in ADJ compared to NC and GC ( P <0.01); we did not observe a significant difference in the expression of this miRNA between NC and GC. This feature may be an antitumor mechanism used by cancer-adjacent tissue because this miRNA regulates the BCL-2 , CDC42 and DMNT3A oncogenes. The expression level of hsa-miR-204 was associated with Helicobacter pylori infection status ( P <0.05) . Functional analysis using the genes regulated by the studied miRNAs showed that they are involved in biological pathways and cellular processes that are critical for the establishment of H. pylori infection and for the onset, development an...

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Section: Discussionmentioning

confidence: 99%

Epigenetic Field Cancerization in Gastric Cancer: microRNAs as Promising Biomarkers

et al. 2019

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“…Previous evaluations obtained by qPCR method on intestinal GCs gave variable results with reports ranging from a clear decrease [11, 21] to a non-significant difference [22, 23] in CDH1 expression in cancer compared to the normal counterpart. Therefore, through the implementation of the more precise dPCR in our quantification, we were able to provide evidence on the downregulation of CDH1 expression.…”

Section: Discussionmentioning

confidence: 99%

“…A number of studies have shown that Helicobacter pylori ( H. pylori ), which is a primary risk factor for IGC, partially mediates the transformation of the normal gastric mucosa by targeting CDH1 transcription and protein expression levels [8, 11, 12]. Small regulatory RNAs (micro-RNAs) have also been associated with a decrease of E-cadherin expression in IGC; in particular, the loss of miR-101 results in the up-regulation of EZH2, an inhibitor of E-cadherin, thus reducing its expression and promoting tumor progression [13].…”

Section: Introductionmentioning

confidence: 99%

Digital PCR identifies changes in CDH1 (E-cadherin) transcription pattern in intestinal-type gastric cancer

et al. 2016

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E-cadherin is a cell-cell adhesion protein encoded by CDH1 tumor-suppressor gene. CDH1 inactivating mutations, leading to loss of protein expression, are common in gastric cancer of the diffuse histotype, while alternative mechanisms modulating E-cadherin expression characterize the more common intestinal histotype. These mechanisms are still poorly understood. CDH1 intron 2 has recently emerged as a cis-modulator of E-cadherin expression, encoding non-canonical transcripts. One in particular, CDH1a, proved to be expressed in gastric cancer cell lines, while being absent in the normal stomach. For the first time, we evaluated by digital PCR the expression of CDH1 and CDH1a transcripts in cancer and normal tissue samples from 32 patients with intestinal-type gastric cancer. We found a significant decrease in CDH1 expression in tumors compared to normal counterparts (P = 0.001), which was especially evident in 76% of cases. CDH1a was detected at extremely low levels in 47% of tumors, but not in normal mucosa. A trend was observed of having less CDH1 in tumors expressing CDH1atranscript. The majority of tumors with both a decrease in CDH1 and presence of CDH1a also showed a decrease in miR-101 expression levels. On the whole, the decrease of CDH1 transcript, corresponding to the canonical protein, and the presence of CDH1a, corresponding to an alternative isoform, are likely to perturb E-cadherin-mediated signaling and cell-cell adhesion, thus contributing to intestinal-type gastric carcinogenesis.

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“…From a molecular genetic perspective, both H. pylori infection [ 29 ] and LPR [ 30 ] are associated with a decreased expression of E-cadherin . This can then reduce the apoptosis of HEp-2 cells, which are considered to originate from human laryngeal carcinoma [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Laryngeal Helicobacter pylori Infection and Laryngeal Cancer-Case Series and a Systematic Review

et al. 2021

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Helicobacter pylori (H. pylori) infection involves the development of gastric cancer and may be associated with laryngeal cancer. However, laryngeal H. pylori infection in Taiwanese patients with newly diagnosed laryngeal cancer has not been reported. This study was aimed to investigate the possible association between laryngeal H. pylori infection and laryngeal cancer in Taiwan and perform a systematic review of previous reports in other countries. An analysis of 105 patients with laryngeal lesions found the positive rates of H. pylori DNA (determined by polymerase chain reaction) and antigen (determined by immunohistochemistry) of the laryngeal lesions were relatively low (vocal polyps: 3% and 3%; vocal fold leukoplakia: 0% and 0%; laryngeal cancers: 0% and 2%). Furthermore, H. pylori-associated laryngopharyngeal reflux and the expression of E-cadherin and CD1d (determined by immunohistochemistry) were comparable among the three subgroups. Fifteen studies were involved in the systematic review of the digital literature database, distributed to February 2021. The data of patients with laryngeal cancer and controls showed that the laryngeal H. pylori infection rates were 29.4% and 16.7%, respectively. Although current evidence supported that laryngeal H. pylori infection was associated with laryngeal cancer globally, it might not play a role in the development of laryngeal cancer in Taiwan.

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Downregulated Expression of E-cadherin and TP53 in Patients with Gastric Diseases: the Involvement of H. pylori Infection and Its Virulence Markers

Abstract: No evidence was found of the involvement of the cagA and vacA genes in the decreased expression of E-cadherin and TP53. The process of carcinogenesis is complex, and the decrease of the E-cadherin gene expression and TP53 gene expression appears to contribute significantly.

Cited by 6 publications

References 36 publications

Epigenetic Field Cancerization in Gastric Cancer: microRNAs as Promising Biomarkers

Epigenetic Field Cancerization in Gastric Cancer: microRNAs as Promising Biomarkers

Digital PCR identifies changes in CDH1 (E-cadherin) transcription pattern in intestinal-type gastric cancer

Laryngeal Helicobacter pylori Infection and Laryngeal Cancer-Case Series and a Systematic Review

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