MiRNA-200c, MiRNA-139 and ln RNA H19; new predictors of treatment response in H-pylori- induced gastric ulcer or progression to gastric cancer
Recent evidence indicates that the pathogenesis of gastric ulcer and progression to gastric cancer could be attributed to altered inflammatory/immunological response and associated differential non-coding RNAs expression signatures. However, co-expression profiling of lncRNA-miRNAs in GU/GC patients...
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| Veröffentlicht in: | Microbial pathogenesis 2020-12, Vol.149, p.104442-104442, Article 104442 |
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| description | Recent evidence indicates that the pathogenesis of gastric ulcer and progression to gastric cancer could be attributed to altered inflammatory/immunological response and associated differential non-coding RNAs expression signatures. However, co-expression profiling of lncRNA-miRNAs in GU/GC patients are scarcely focused on. Therefore, in the present study the expression of H19 and related miRNAs including miR-139, and miR-200 were assayed in the plasma samples of treatment responsive GU vs nonresponsive GC patients. This study is a case-control study carried out on 130 subjects recruited from the Gastrointestinal Endoscopy Unit in Al-Kasr Al-Aini Hospital, in Egypt. All recruited patients were diagnosed with H-pylori infection, 50 of them were gastric cancer patients (GC), with previous H-pylori induced gastric ulcer but were treatment non-respondent. Real-time PCR was performed to evaluate the expression level of serum non-coding RNA; miRNA-200c, miR-139, Ln RNA H19 in patients with peptic ulcer treatment non-respondent, who progressed to GC vs non-progressed gastric ulcer patients (GU) (n = 50), and compared to early diagnosed H-pylori-gastric ulcer patients (n = 30). The association between these miRNAs and the FGF-18/FGF-R signaling indicators of H-pylori-GC pathogenesis were then investigated.
showed that the H19 level was significantly elevated while miR-139 and miR-200c expression were significantly down-regulated in GC patients, compared to GU participants (P |
| doi_str_mv | 10.1016/j.micpath.2020.104442 |
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showed that the H19 level was significantly elevated while miR-139 and miR-200c expression were significantly down-regulated in GC patients, compared to GU participants (P < 0.01). The herein investigated ncRNAs are correlated to the disease duration with Ln H19 being significantly correlated with all inflammatory markers; TNF-α, INF-γ, TAC, MMP-9, and FGF18/FGFR2. A significant correlation was also observed between miRNA 200c and each of miRNA 139 and FGFR2. Moreover, ROC analysis revealed that miRNA 200c showed the highest AUC (0.906) and 81.2% sensitivity and 100% specificity. Moreover, the combined analysis of miRNA 200c/miRNA 139 revealed superior AUC (0.96) and 93% sensitivity and 100% specificity, than each separately. As for discriminative accuracy between stages III to IV of gastric cancer, LncRNA H19 showed the highest diagnostic accuracy (95.5%), specificity (100%), and sensitivity (90.9%). The current study demonstrated that the combination of serum miRNA 200c/miRNA 139 expression levels (down-regulation) could provide a new potential prognostic panel for GU predictive response and potential sequelae. In conclusion, LncRNA H19 and related miRNAs, miRNA 200c/miRNA 139, could serve as a potential diagnostic biomarker for early gastric cancer diagnosis.
•This study is a case-control study assessing the expression levels of serum miR-200c, miR-139 and Ln RNA H19 in treated peptic ulcer patients vs those who progressed to gastric cancer.•The signaling mediators that are expected to be targeted by the ncRNAs are FGF-18, that is affected by Ln H19, added to BCL2 and MMPs, both have a potential regulatory role on miR-139.•The NF-κB –MEK/ ERK pathway is targeted by LnH19, while ROS and TNF-α are impacted by miR-200c.•Moreover, the correlation of the aforementioned markers with the studied ncRNAs and their predictive and prognostic value in the progression of H pylori peptic ulcer to gastric cancer have been studied.</description><identifier>ISSN: 0882-4010</identifier><identifier>EISSN: 1096-1208</identifier><identifier>DOI: 10.1016/j.micpath.2020.104442</identifier><identifier>PMID: 32795593</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Biomarkers, Tumor - genetics ; Case-Control Studies ; Egypt ; Gastric cancer ; H. pylori-peptic ulcer ; Humans ; LncRNA H19 ; MicroRNAs - genetics ; miR-139 ; miR-200c ; RNA, Long Noncoding - genetics ; Stomach Neoplasms - genetics ; Stomach Ulcer - genetics</subject><ispartof>Microbial pathogenesis, 2020-12, Vol.149, p.104442-104442, Article 104442</ispartof><rights>2020 Elsevier Ltd</rights><rights>Copyright © 2020 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-de80d080a13ebd5168f098c394c50f377ff4d1016432c3eb201df4fcb836b2a83</citedby><cites>FETCH-LOGICAL-c365t-de80d080a13ebd5168f098c394c50f377ff4d1016432c3eb201df4fcb836b2a83</cites><orcidid>0000-0002-8569-689X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0882401020308081$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32795593$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schaalan, Mona</creatorcontrib><creatorcontrib>Mohamed, Waleed</creatorcontrib><creatorcontrib>Fathy, Shimaa</creatorcontrib><title>MiRNA-200c, MiRNA-139 and ln RNA H19; new predictors of treatment response in H-pylori- induced gastric ulcer or progression to gastric cancer</title><title>Microbial pathogenesis</title><addtitle>Microb Pathog</addtitle><description>Recent evidence indicates that the pathogenesis of gastric ulcer and progression to gastric cancer could be attributed to altered inflammatory/immunological response and associated differential non-coding RNAs expression signatures. However, co-expression profiling of lncRNA-miRNAs in GU/GC patients are scarcely focused on. Therefore, in the present study the expression of H19 and related miRNAs including miR-139, and miR-200 were assayed in the plasma samples of treatment responsive GU vs nonresponsive GC patients. This study is a case-control study carried out on 130 subjects recruited from the Gastrointestinal Endoscopy Unit in Al-Kasr Al-Aini Hospital, in Egypt. All recruited patients were diagnosed with H-pylori infection, 50 of them were gastric cancer patients (GC), with previous H-pylori induced gastric ulcer but were treatment non-respondent. Real-time PCR was performed to evaluate the expression level of serum non-coding RNA; miRNA-200c, miR-139, Ln RNA H19 in patients with peptic ulcer treatment non-respondent, who progressed to GC vs non-progressed gastric ulcer patients (GU) (n = 50), and compared to early diagnosed H-pylori-gastric ulcer patients (n = 30). The association between these miRNAs and the FGF-18/FGF-R signaling indicators of H-pylori-GC pathogenesis were then investigated.
showed that the H19 level was significantly elevated while miR-139 and miR-200c expression were significantly down-regulated in GC patients, compared to GU participants (P < 0.01). The herein investigated ncRNAs are correlated to the disease duration with Ln H19 being significantly correlated with all inflammatory markers; TNF-α, INF-γ, TAC, MMP-9, and FGF18/FGFR2. A significant correlation was also observed between miRNA 200c and each of miRNA 139 and FGFR2. Moreover, ROC analysis revealed that miRNA 200c showed the highest AUC (0.906) and 81.2% sensitivity and 100% specificity. Moreover, the combined analysis of miRNA 200c/miRNA 139 revealed superior AUC (0.96) and 93% sensitivity and 100% specificity, than each separately. As for discriminative accuracy between stages III to IV of gastric cancer, LncRNA H19 showed the highest diagnostic accuracy (95.5%), specificity (100%), and sensitivity (90.9%). The current study demonstrated that the combination of serum miRNA 200c/miRNA 139 expression levels (down-regulation) could provide a new potential prognostic panel for GU predictive response and potential sequelae. In conclusion, LncRNA H19 and related miRNAs, miRNA 200c/miRNA 139, could serve as a potential diagnostic biomarker for early gastric cancer diagnosis.
•This study is a case-control study assessing the expression levels of serum miR-200c, miR-139 and Ln RNA H19 in treated peptic ulcer patients vs those who progressed to gastric cancer.•The signaling mediators that are expected to be targeted by the ncRNAs are FGF-18, that is affected by Ln H19, added to BCL2 and MMPs, both have a potential regulatory role on miR-139.•The NF-κB –MEK/ ERK pathway is targeted by LnH19, while ROS and TNF-α are impacted by miR-200c.•Moreover, the correlation of the aforementioned markers with the studied ncRNAs and their predictive and prognostic value in the progression of H pylori peptic ulcer to gastric cancer have been studied.</description><subject>Biomarkers, Tumor - genetics</subject><subject>Case-Control Studies</subject><subject>Egypt</subject><subject>Gastric cancer</subject><subject>H. pylori-peptic ulcer</subject><subject>Humans</subject><subject>LncRNA H19</subject><subject>MicroRNAs - genetics</subject><subject>miR-139</subject><subject>miR-200c</subject><subject>RNA, Long Noncoding - genetics</subject><subject>Stomach Neoplasms - genetics</subject><subject>Stomach Ulcer - genetics</subject><issn>0882-4010</issn><issn>1096-1208</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc2OFCEUhYnROO3oI2hYurDay09VQ1yYyURtk1ETo2tCw62RTlVRAqWZl_CZpVPtbF3Bhe_eA-cQ8pzBlgHrXh-3Y3CzLT-2HPjpTErJH5ANA901jIN6SDagFG8kMLggT3I-AoCWQj8mF4LvdNtqsSF_PoWvn68aDuBe0XXPhKZ28nSYaC3pnuk3dMLfdE7ogysxZRp7WhLaMuJUaMI8xykjDRPdN_PdEFNoauEXh57e2lxScHQZHCYaUx0Tb2tLDnGiJd7fOztV4Cl51Nsh47Pzekm-v3_37Xrf3Hz58PH66qZxomtL41GBBwWWCTz4lnWqB62c0NK10Ivdru-lP9kkBXcV4cB8L3t3UKI7cKvEJXm5zq2v-blgLmYM2eEw2Anjkg2XQsod00pXtF1Rl2LOCXszpzDadGcYmJOGOZpzFOYUhVmjqH0vzhLLYUR_3_XP-wq8XQGsH_0VMJnsAlYXfEjoivEx_EfiL-nKm24</recordid><startdate>202012</startdate><enddate>202012</enddate><creator>Schaalan, Mona</creator><creator>Mohamed, Waleed</creator><creator>Fathy, Shimaa</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-8569-689X</orcidid></search><sort><creationdate>202012</creationdate><title>MiRNA-200c, MiRNA-139 and ln RNA H19; new predictors of treatment response in H-pylori- induced gastric ulcer or progression to gastric cancer</title><author>Schaalan, Mona ; Mohamed, Waleed ; Fathy, Shimaa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-de80d080a13ebd5168f098c394c50f377ff4d1016432c3eb201df4fcb836b2a83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Biomarkers, Tumor - genetics</topic><topic>Case-Control Studies</topic><topic>Egypt</topic><topic>Gastric cancer</topic><topic>H. pylori-peptic ulcer</topic><topic>Humans</topic><topic>LncRNA H19</topic><topic>MicroRNAs - genetics</topic><topic>miR-139</topic><topic>miR-200c</topic><topic>RNA, Long Noncoding - genetics</topic><topic>Stomach Neoplasms - genetics</topic><topic>Stomach Ulcer - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schaalan, Mona</creatorcontrib><creatorcontrib>Mohamed, Waleed</creatorcontrib><creatorcontrib>Fathy, Shimaa</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Microbial pathogenesis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schaalan, Mona</au><au>Mohamed, Waleed</au><au>Fathy, Shimaa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MiRNA-200c, MiRNA-139 and ln RNA H19; new predictors of treatment response in H-pylori- induced gastric ulcer or progression to gastric cancer</atitle><jtitle>Microbial pathogenesis</jtitle><addtitle>Microb Pathog</addtitle><date>2020-12</date><risdate>2020</risdate><volume>149</volume><spage>104442</spage><epage>104442</epage><pages>104442-104442</pages><artnum>104442</artnum><issn>0882-4010</issn><eissn>1096-1208</eissn><abstract>Recent evidence indicates that the pathogenesis of gastric ulcer and progression to gastric cancer could be attributed to altered inflammatory/immunological response and associated differential non-coding RNAs expression signatures. However, co-expression profiling of lncRNA-miRNAs in GU/GC patients are scarcely focused on. Therefore, in the present study the expression of H19 and related miRNAs including miR-139, and miR-200 were assayed in the plasma samples of treatment responsive GU vs nonresponsive GC patients. This study is a case-control study carried out on 130 subjects recruited from the Gastrointestinal Endoscopy Unit in Al-Kasr Al-Aini Hospital, in Egypt. All recruited patients were diagnosed with H-pylori infection, 50 of them were gastric cancer patients (GC), with previous H-pylori induced gastric ulcer but were treatment non-respondent. Real-time PCR was performed to evaluate the expression level of serum non-coding RNA; miRNA-200c, miR-139, Ln RNA H19 in patients with peptic ulcer treatment non-respondent, who progressed to GC vs non-progressed gastric ulcer patients (GU) (n = 50), and compared to early diagnosed H-pylori-gastric ulcer patients (n = 30). The association between these miRNAs and the FGF-18/FGF-R signaling indicators of H-pylori-GC pathogenesis were then investigated.
showed that the H19 level was significantly elevated while miR-139 and miR-200c expression were significantly down-regulated in GC patients, compared to GU participants (P < 0.01). The herein investigated ncRNAs are correlated to the disease duration with Ln H19 being significantly correlated with all inflammatory markers; TNF-α, INF-γ, TAC, MMP-9, and FGF18/FGFR2. A significant correlation was also observed between miRNA 200c and each of miRNA 139 and FGFR2. Moreover, ROC analysis revealed that miRNA 200c showed the highest AUC (0.906) and 81.2% sensitivity and 100% specificity. Moreover, the combined analysis of miRNA 200c/miRNA 139 revealed superior AUC (0.96) and 93% sensitivity and 100% specificity, than each separately. As for discriminative accuracy between stages III to IV of gastric cancer, LncRNA H19 showed the highest diagnostic accuracy (95.5%), specificity (100%), and sensitivity (90.9%). The current study demonstrated that the combination of serum miRNA 200c/miRNA 139 expression levels (down-regulation) could provide a new potential prognostic panel for GU predictive response and potential sequelae. In conclusion, LncRNA H19 and related miRNAs, miRNA 200c/miRNA 139, could serve as a potential diagnostic biomarker for early gastric cancer diagnosis.
•This study is a case-control study assessing the expression levels of serum miR-200c, miR-139 and Ln RNA H19 in treated peptic ulcer patients vs those who progressed to gastric cancer.•The signaling mediators that are expected to be targeted by the ncRNAs are FGF-18, that is affected by Ln H19, added to BCL2 and MMPs, both have a potential regulatory role on miR-139.•The NF-κB –MEK/ ERK pathway is targeted by LnH19, while ROS and TNF-α are impacted by miR-200c.•Moreover, the correlation of the aforementioned markers with the studied ncRNAs and their predictive and prognostic value in the progression of H pylori peptic ulcer to gastric cancer have been studied.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>32795593</pmid><doi>10.1016/j.micpath.2020.104442</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-8569-689X</orcidid></addata></record> |
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| subjects | Biomarkers, Tumor - genetics Case-Control Studies Egypt Gastric cancer H. pylori-peptic ulcer Humans LncRNA H19 MicroRNAs - genetics miR-139 miR-200c RNA, Long Noncoding - genetics Stomach Neoplasms - genetics Stomach Ulcer - genetics |
| title | MiRNA-200c, MiRNA-139 and ln RNA H19; new predictors of treatment response in H-pylori- induced gastric ulcer or progression to gastric cancer |
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