Genomic features of Helicobacter pylori‐naïve diffuse‐type gastric cancer
Helicobacter pylori (HP) is a major etiologic driver of diffuse‐type gastric cancer (DGC). However, improvements in hygiene have led to an increase in the prevalence of HP‐naïve DGC; that is, DGC that occurs independent of HP. Although multiple genomic cohort studies for gastric cancer have been con...
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| Veröffentlicht in: | The Journal of pathology 2022-11, Vol.258 (3), p.300-311 |
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| creator | Namikawa, Ken Tanaka, Norio Ota, Yuki Takamatsu, Manabu Kosugi, Mayuko Tokai, Yoshitaka Yoshimizu, Shoichi Horiuchi, Yusuke Ishiyama, Akiyoshi Yoshio, Toshiyuki Hirasawa, Toshiaki Amino, Sayuri Furuya, Rie Gotoh, Osamu Kaneyasu, Tomoko Nakayama, Izuma Imamura, Yu Noda, Tetsuo Fujisaki, Junko Mori, Seiichi |
| description | Helicobacter pylori (HP) is a major etiologic driver of diffuse‐type gastric cancer (DGC). However, improvements in hygiene have led to an increase in the prevalence of HP‐naïve DGC; that is, DGC that occurs independent of HP. Although multiple genomic cohort studies for gastric cancer have been conducted, including studies for DGC, distinctive genomic differences between HP‐exposed and HP‐naïve DGC remain largely unknown. Here, we employed exome and RNA sequencing with immunohistochemical analyses to perform binary comparisons between 36 HP‐exposed and 27 HP‐naïve DGCs from sporadic, early‐stage, and intramucosal or submucosal tumor samples. Among the samples, 33 HP‐exposed and 17 HP‐naïve samples had been preserved as fresh‐frozen samples. HP infection status was determined using stringent criteria. HP‐exposed DGCs exhibited an increased single nucleotide variant burden (HP‐exposed DGCs; 1.97 [0.48–7.19] and HP‐naïve DGCs; 1.09 [0.38–3.68] per megabase; p = 0.0003) and a higher prevalence of chromosome arm‐level aneuploidies (p |
| doi_str_mv | 10.1002/path.6000 |
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However, improvements in hygiene have led to an increase in the prevalence of HP‐naïve DGC; that is, DGC that occurs independent of HP. Although multiple genomic cohort studies for gastric cancer have been conducted, including studies for DGC, distinctive genomic differences between HP‐exposed and HP‐naïve DGC remain largely unknown. Here, we employed exome and RNA sequencing with immunohistochemical analyses to perform binary comparisons between 36 HP‐exposed and 27 HP‐naïve DGCs from sporadic, early‐stage, and intramucosal or submucosal tumor samples. Among the samples, 33 HP‐exposed and 17 HP‐naïve samples had been preserved as fresh‐frozen samples. HP infection status was determined using stringent criteria. HP‐exposed DGCs exhibited an increased single nucleotide variant burden (HP‐exposed DGCs; 1.97 [0.48–7.19] and HP‐naïve DGCs; 1.09 [0.38–3.68] per megabase; p = 0.0003) and a higher prevalence of chromosome arm‐level aneuploidies (p < 0.0001). CDH1 was mutated at similar frequencies in both groups, whereas the RHOA–ARHGAP pathway misregulation was exclusive to HP‐exposed DGCs (p = 0.0167). HP‐exposed DGCs showed gains in chromosome arms 8p/8q (p < 0.0001), 7p (p = 0.0035), and 7q (p = 0.0354), and losses in 16q (p = 0.0167). Immunohistochemical analyses revealed a higher expression of intestinal markers such as CD10 (p < 0.0001) and CDX2 (p = 0.0002) and a lower expression of the gastric marker, MUC5AC (p = 0.0305) among HP‐exposed DGCs. HP‐naïve DGCs, on the other hand, had a purely gastric marker phenotype. This work reveals that HP‐naïve and HP‐exposed DGCs develop along different molecular pathways, which provide a basis for early detection strategies in high incidence settings. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.</description><identifier>ISSN: 0022-3417</identifier><identifier>EISSN: 1096-9896</identifier><identifier>DOI: 10.1002/path.6000</identifier><identifier>PMID: 36111561</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>CDX2 protein ; chromosome arm‐level aneuploidy ; Chromosomes ; diffuse‐type gastric cancer ; E-cadherin ; exome sequencing ; Gastric cancer ; gastric marker ; Gastric Mucosa - pathology ; Genomics ; Helicobacter Infections - complications ; Helicobacter pylori ; Helicobacter pylori - genetics ; Humans ; Hygiene ; immunohistochemistry ; intestinal marker ; Nucleotides - metabolism ; Original ; Phenotypes ; RhoA protein ; RHOA–ARHGAP pathway ; RNA sequencing ; Stomach Neoplasms - pathology ; Tumors</subject><ispartof>The Journal of pathology, 2022-11, Vol.258 (3), p.300-311</ispartof><rights>2022 The Authors. published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.</rights><rights>2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.</rights><rights>2022. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5090-f0b522a4ba188b7fd12e5acd2e0745fa832dde170f7fc5cecd861e0e6f859a163</citedby><cites>FETCH-LOGICAL-c5090-f0b522a4ba188b7fd12e5acd2e0745fa832dde170f7fc5cecd861e0e6f859a163</cites><orcidid>0000-0002-9363-4584 ; 0000-0003-2724-8009</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpath.6000$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpath.6000$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36111561$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Namikawa, Ken</creatorcontrib><creatorcontrib>Tanaka, Norio</creatorcontrib><creatorcontrib>Ota, Yuki</creatorcontrib><creatorcontrib>Takamatsu, Manabu</creatorcontrib><creatorcontrib>Kosugi, Mayuko</creatorcontrib><creatorcontrib>Tokai, Yoshitaka</creatorcontrib><creatorcontrib>Yoshimizu, Shoichi</creatorcontrib><creatorcontrib>Horiuchi, Yusuke</creatorcontrib><creatorcontrib>Ishiyama, Akiyoshi</creatorcontrib><creatorcontrib>Yoshio, Toshiyuki</creatorcontrib><creatorcontrib>Hirasawa, Toshiaki</creatorcontrib><creatorcontrib>Amino, Sayuri</creatorcontrib><creatorcontrib>Furuya, Rie</creatorcontrib><creatorcontrib>Gotoh, Osamu</creatorcontrib><creatorcontrib>Kaneyasu, Tomoko</creatorcontrib><creatorcontrib>Nakayama, Izuma</creatorcontrib><creatorcontrib>Imamura, Yu</creatorcontrib><creatorcontrib>Noda, Tetsuo</creatorcontrib><creatorcontrib>Fujisaki, Junko</creatorcontrib><creatorcontrib>Mori, Seiichi</creatorcontrib><title>Genomic features of Helicobacter pylori‐naïve diffuse‐type gastric cancer</title><title>The Journal of pathology</title><addtitle>J Pathol</addtitle><description>Helicobacter pylori (HP) is a major etiologic driver of diffuse‐type gastric cancer (DGC). However, improvements in hygiene have led to an increase in the prevalence of HP‐naïve DGC; that is, DGC that occurs independent of HP. Although multiple genomic cohort studies for gastric cancer have been conducted, including studies for DGC, distinctive genomic differences between HP‐exposed and HP‐naïve DGC remain largely unknown. Here, we employed exome and RNA sequencing with immunohistochemical analyses to perform binary comparisons between 36 HP‐exposed and 27 HP‐naïve DGCs from sporadic, early‐stage, and intramucosal or submucosal tumor samples. Among the samples, 33 HP‐exposed and 17 HP‐naïve samples had been preserved as fresh‐frozen samples. HP infection status was determined using stringent criteria. HP‐exposed DGCs exhibited an increased single nucleotide variant burden (HP‐exposed DGCs; 1.97 [0.48–7.19] and HP‐naïve DGCs; 1.09 [0.38–3.68] per megabase; p = 0.0003) and a higher prevalence of chromosome arm‐level aneuploidies (p < 0.0001). CDH1 was mutated at similar frequencies in both groups, whereas the RHOA–ARHGAP pathway misregulation was exclusive to HP‐exposed DGCs (p = 0.0167). HP‐exposed DGCs showed gains in chromosome arms 8p/8q (p < 0.0001), 7p (p = 0.0035), and 7q (p = 0.0354), and losses in 16q (p = 0.0167). Immunohistochemical analyses revealed a higher expression of intestinal markers such as CD10 (p < 0.0001) and CDX2 (p = 0.0002) and a lower expression of the gastric marker, MUC5AC (p = 0.0305) among HP‐exposed DGCs. HP‐naïve DGCs, on the other hand, had a purely gastric marker phenotype. This work reveals that HP‐naïve and HP‐exposed DGCs develop along different molecular pathways, which provide a basis for early detection strategies in high incidence settings. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.</description><subject>CDX2 protein</subject><subject>chromosome arm‐level aneuploidy</subject><subject>Chromosomes</subject><subject>diffuse‐type gastric cancer</subject><subject>E-cadherin</subject><subject>exome sequencing</subject><subject>Gastric cancer</subject><subject>gastric marker</subject><subject>Gastric Mucosa - pathology</subject><subject>Genomics</subject><subject>Helicobacter Infections - complications</subject><subject>Helicobacter pylori</subject><subject>Helicobacter pylori - genetics</subject><subject>Humans</subject><subject>Hygiene</subject><subject>immunohistochemistry</subject><subject>intestinal marker</subject><subject>Nucleotides - metabolism</subject><subject>Original</subject><subject>Phenotypes</subject><subject>RhoA protein</subject><subject>RHOA–ARHGAP pathway</subject><subject>RNA sequencing</subject><subject>Stomach Neoplasms - pathology</subject><subject>Tumors</subject><issn>0022-3417</issn><issn>1096-9896</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp10UFO3DAUBmCrKipT2gUXqCJ1UxaBZ8_YjjdICBUGCdEu6NpynGcwysSpnVDNrkfoTXqI3oST4DAUUaSuLPl9_vWsn5BdCvsUgB30ZrjeFwDwiswoKFGqSonXZJZnrJwvqNwmb1O6yUApzt-Q7bmglHJBZ-TiFLuw8rZwaIYxYiqCK5bYehtqYweMRb9uQ_R3P3915s_vWywa79yYMF8M6x6LK5OGmN9b01mM78iWM23C94_nDvl28vnyeFmefzk9Oz46Ly0HBaWDmjNmFrWhVVVL11CG3NiGIcgFd6aas6ZBKsFJZ7lF21SCIqBwFVeGivkOOdzk9mO9wsZiN0TT6j76lYlrHYzX_046f62vwq1WFeNKQQ749BgQw_cR06BXPllsW9NhGJNmklEmgC1Yph9f0Jswxi5_b1IguZRiUnsbZWNIKaJ7WoaCnlrSU0t6ainbD8-3f5J_a8ngYAN--BbX_0_SX48ulw-R9xVqoKA</recordid><startdate>202211</startdate><enddate>202211</enddate><creator>Namikawa, Ken</creator><creator>Tanaka, Norio</creator><creator>Ota, Yuki</creator><creator>Takamatsu, Manabu</creator><creator>Kosugi, Mayuko</creator><creator>Tokai, Yoshitaka</creator><creator>Yoshimizu, Shoichi</creator><creator>Horiuchi, Yusuke</creator><creator>Ishiyama, Akiyoshi</creator><creator>Yoshio, Toshiyuki</creator><creator>Hirasawa, Toshiaki</creator><creator>Amino, Sayuri</creator><creator>Furuya, Rie</creator><creator>Gotoh, Osamu</creator><creator>Kaneyasu, Tomoko</creator><creator>Nakayama, Izuma</creator><creator>Imamura, Yu</creator><creator>Noda, Tetsuo</creator><creator>Fujisaki, Junko</creator><creator>Mori, Seiichi</creator><general>John Wiley & Sons, Ltd</general><general>Wiley Subscription Services, Inc</general><scope>24P</scope><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>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-9363-4584</orcidid><orcidid>https://orcid.org/0000-0003-2724-8009</orcidid></search><sort><creationdate>202211</creationdate><title>Genomic features of Helicobacter pylori‐naïve diffuse‐type gastric cancer</title><author>Namikawa, Ken ; Tanaka, Norio ; Ota, Yuki ; Takamatsu, Manabu ; Kosugi, Mayuko ; Tokai, Yoshitaka ; Yoshimizu, Shoichi ; Horiuchi, Yusuke ; Ishiyama, Akiyoshi ; Yoshio, Toshiyuki ; Hirasawa, Toshiaki ; Amino, Sayuri ; Furuya, Rie ; Gotoh, Osamu ; Kaneyasu, Tomoko ; Nakayama, Izuma ; Imamura, Yu ; Noda, Tetsuo ; Fujisaki, Junko ; Mori, Seiichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5090-f0b522a4ba188b7fd12e5acd2e0745fa832dde170f7fc5cecd861e0e6f859a163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>CDX2 protein</topic><topic>chromosome arm‐level aneuploidy</topic><topic>Chromosomes</topic><topic>diffuse‐type gastric cancer</topic><topic>E-cadherin</topic><topic>exome sequencing</topic><topic>Gastric cancer</topic><topic>gastric marker</topic><topic>Gastric Mucosa - pathology</topic><topic>Genomics</topic><topic>Helicobacter Infections - complications</topic><topic>Helicobacter pylori</topic><topic>Helicobacter pylori - genetics</topic><topic>Humans</topic><topic>Hygiene</topic><topic>immunohistochemistry</topic><topic>intestinal marker</topic><topic>Nucleotides - metabolism</topic><topic>Original</topic><topic>Phenotypes</topic><topic>RhoA protein</topic><topic>RHOA–ARHGAP pathway</topic><topic>RNA sequencing</topic><topic>Stomach Neoplasms - pathology</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Namikawa, Ken</creatorcontrib><creatorcontrib>Tanaka, Norio</creatorcontrib><creatorcontrib>Ota, Yuki</creatorcontrib><creatorcontrib>Takamatsu, Manabu</creatorcontrib><creatorcontrib>Kosugi, Mayuko</creatorcontrib><creatorcontrib>Tokai, Yoshitaka</creatorcontrib><creatorcontrib>Yoshimizu, Shoichi</creatorcontrib><creatorcontrib>Horiuchi, Yusuke</creatorcontrib><creatorcontrib>Ishiyama, Akiyoshi</creatorcontrib><creatorcontrib>Yoshio, Toshiyuki</creatorcontrib><creatorcontrib>Hirasawa, Toshiaki</creatorcontrib><creatorcontrib>Amino, Sayuri</creatorcontrib><creatorcontrib>Furuya, Rie</creatorcontrib><creatorcontrib>Gotoh, Osamu</creatorcontrib><creatorcontrib>Kaneyasu, Tomoko</creatorcontrib><creatorcontrib>Nakayama, Izuma</creatorcontrib><creatorcontrib>Imamura, Yu</creatorcontrib><creatorcontrib>Noda, Tetsuo</creatorcontrib><creatorcontrib>Fujisaki, Junko</creatorcontrib><creatorcontrib>Mori, Seiichi</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Namikawa, Ken</au><au>Tanaka, Norio</au><au>Ota, Yuki</au><au>Takamatsu, Manabu</au><au>Kosugi, Mayuko</au><au>Tokai, Yoshitaka</au><au>Yoshimizu, Shoichi</au><au>Horiuchi, Yusuke</au><au>Ishiyama, Akiyoshi</au><au>Yoshio, Toshiyuki</au><au>Hirasawa, Toshiaki</au><au>Amino, Sayuri</au><au>Furuya, Rie</au><au>Gotoh, Osamu</au><au>Kaneyasu, Tomoko</au><au>Nakayama, Izuma</au><au>Imamura, Yu</au><au>Noda, Tetsuo</au><au>Fujisaki, Junko</au><au>Mori, Seiichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genomic features of Helicobacter pylori‐naïve diffuse‐type gastric cancer</atitle><jtitle>The Journal of pathology</jtitle><addtitle>J Pathol</addtitle><date>2022-11</date><risdate>2022</risdate><volume>258</volume><issue>3</issue><spage>300</spage><epage>311</epage><pages>300-311</pages><issn>0022-3417</issn><eissn>1096-9896</eissn><abstract>Helicobacter pylori (HP) is a major etiologic driver of diffuse‐type gastric cancer (DGC). However, improvements in hygiene have led to an increase in the prevalence of HP‐naïve DGC; that is, DGC that occurs independent of HP. Although multiple genomic cohort studies for gastric cancer have been conducted, including studies for DGC, distinctive genomic differences between HP‐exposed and HP‐naïve DGC remain largely unknown. Here, we employed exome and RNA sequencing with immunohistochemical analyses to perform binary comparisons between 36 HP‐exposed and 27 HP‐naïve DGCs from sporadic, early‐stage, and intramucosal or submucosal tumor samples. Among the samples, 33 HP‐exposed and 17 HP‐naïve samples had been preserved as fresh‐frozen samples. HP infection status was determined using stringent criteria. HP‐exposed DGCs exhibited an increased single nucleotide variant burden (HP‐exposed DGCs; 1.97 [0.48–7.19] and HP‐naïve DGCs; 1.09 [0.38–3.68] per megabase; p = 0.0003) and a higher prevalence of chromosome arm‐level aneuploidies (p < 0.0001). CDH1 was mutated at similar frequencies in both groups, whereas the RHOA–ARHGAP pathway misregulation was exclusive to HP‐exposed DGCs (p = 0.0167). HP‐exposed DGCs showed gains in chromosome arms 8p/8q (p < 0.0001), 7p (p = 0.0035), and 7q (p = 0.0354), and losses in 16q (p = 0.0167). Immunohistochemical analyses revealed a higher expression of intestinal markers such as CD10 (p < 0.0001) and CDX2 (p = 0.0002) and a lower expression of the gastric marker, MUC5AC (p = 0.0305) among HP‐exposed DGCs. HP‐naïve DGCs, on the other hand, had a purely gastric marker phenotype. This work reveals that HP‐naïve and HP‐exposed DGCs develop along different molecular pathways, which provide a basis for early detection strategies in high incidence settings. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>36111561</pmid><doi>10.1002/path.6000</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-9363-4584</orcidid><orcidid>https://orcid.org/0000-0003-2724-8009</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | CDX2 protein chromosome arm‐level aneuploidy Chromosomes diffuse‐type gastric cancer E-cadherin exome sequencing Gastric cancer gastric marker Gastric Mucosa - pathology Genomics Helicobacter Infections - complications Helicobacter pylori Helicobacter pylori - genetics Humans Hygiene immunohistochemistry intestinal marker Nucleotides - metabolism Original Phenotypes RhoA protein RHOA–ARHGAP pathway RNA sequencing Stomach Neoplasms - pathology Tumors |
| title | Genomic features of Helicobacter pylori‐naïve diffuse‐type gastric cancer |
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