Intratumor stromal proportion predicts aggressive phenotype of gastric signet ring cell carcinomas
Objective The aim of this study was to evaluate the prognostic significance of the intratumor stromal proportion in gastric signet ring cell (SRC) carcinomas. Background Cancer stroma, as exemplified by cancer-associated fibroblasts (CAFs), plays critical roles in cancer proliferation, invasion, and...
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| Veröffentlicht in: | Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 2017-07, Vol.20 (4), p.591-601 |
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| creator | Lee, Dakeun Ham, In-Hye Son, Sang Yong Han, Sang-Uk Kim, Young-Bae Hur, Hoon |
| description | Objective
The aim of this study was to evaluate the prognostic significance of the intratumor stromal proportion in gastric signet ring cell (SRC) carcinomas.
Background
Cancer stroma, as exemplified by cancer-associated fibroblasts (CAFs), plays critical roles in cancer proliferation, invasion, and metastasis.
Methods
One hundred seventy-five SRC carcinoma cases were classified according to the intratumor desmoplastic stromal proportion to then analyze the clinicopathologic characteristics of stroma-rich cases. We also investigated the impact of CAFs on the migration as well as on the phenotypic changes of gastric SRC carcinomas in vitro. Furthermore, we performed RNA sequencing of a pair of CAFs and normal-tissue-associated fibroblasts.
Results
Stroma-rich SRC carcinomas (64 of 175 cases, 36.5%) were associated with female patients (
P
= 0.045), large tumor size (
P
= 0.007), higher T category (
P
|
| doi_str_mv | 10.1007/s10120-016-0669-2 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1841804401</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1841804401</sourcerecordid><originalsourceid>FETCH-LOGICAL-c532t-76a48eb27014cabc122bade32ec1433b3dce0987c42e647944e7ff6bf946a7243</originalsourceid><addsrcrecordid>eNp1kUFP3DAQhS1UBMvCD-gFWeqllxSP49jJESEKK63UC5wtxztJjTZxsB0k_n0dLSCE1JPn8N7nN_MI-Q7sFzCmriIw4KxgIAsmZVPwI7ICUcqiLFn17X3mDZySsxifGIOqAXlCTrmqqxpqWJF2M6Zg0jz4QGMKfjB7OgU_-ZCcH_OIO2dTpKbvA8boXpBOf3H06XVC6jvam-xylkbXj5hocGNPLe731Jpg3Zh58Zwcd2Yf8eLtXZPH37cPN_fF9s_d5uZ6W9iq5KlQ0ogaW64YCGtaC5y3ZoclR5v3KNtyZ5E1tbKCoxSqEQJV18m2a4Q0iotyTX4euDn_84wx6cHFJYsZ0c9RQy2gZkIwyNIfX6RPfg5jTqehAS5qVbEFCAeVDT7GgJ2eghtMeNXA9FKAPhSgcwF6KUDz7Ll8I8_tgLsPx_vFs4AfBHFajoXh09f_pf4DsraRyg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1912487504</pqid></control><display><type>article</type><title>Intratumor stromal proportion predicts aggressive phenotype of gastric signet ring cell carcinomas</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>SpringerLink Journals - AutoHoldings</source><creator>Lee, Dakeun ; Ham, In-Hye ; Son, Sang Yong ; Han, Sang-Uk ; Kim, Young-Bae ; Hur, Hoon</creator><creatorcontrib>Lee, Dakeun ; Ham, In-Hye ; Son, Sang Yong ; Han, Sang-Uk ; Kim, Young-Bae ; Hur, Hoon</creatorcontrib><description>Objective
The aim of this study was to evaluate the prognostic significance of the intratumor stromal proportion in gastric signet ring cell (SRC) carcinomas.
Background
Cancer stroma, as exemplified by cancer-associated fibroblasts (CAFs), plays critical roles in cancer proliferation, invasion, and metastasis.
Methods
One hundred seventy-five SRC carcinoma cases were classified according to the intratumor desmoplastic stromal proportion to then analyze the clinicopathologic characteristics of stroma-rich cases. We also investigated the impact of CAFs on the migration as well as on the phenotypic changes of gastric SRC carcinomas in vitro. Furthermore, we performed RNA sequencing of a pair of CAFs and normal-tissue-associated fibroblasts.
Results
Stroma-rich SRC carcinomas (64 of 175 cases, 36.5%) were associated with female patients (
P
= 0.045), large tumor size (
P
= 0.007), higher T category (
P
< 0.001), and the presence of perineural invasion (
P
= 0.018). Patients with stroma-rich SRC carcinomas had a significantly shorter disease-free survival (
P
< 0.001) and overall survival (
P
< 0.001). However, in a subgroup analysis, the prognostic significance of the stromal proportion correlated only with patients with T3/4 disease. From multivariate analysis, the high stromal proportion is an independent prognostic factor to predict worse disease-free survival (hazard ratio 2.288;
P
= 0.001) and overall survival (hazard ratio 2.503;
P
= 0.001). We found that CAFs enhanced the migratory abilities of cancer cells through the epithelial–mesenchymal transition, and RNA sequencing results confirmed these findings.
Conclusions
The intratumor stromal proportion could be a useful prognostic biomarker and a potential therapeutic target in gastric SRC carcinomas.</description><identifier>ISSN: 1436-3291</identifier><identifier>EISSN: 1436-3305</identifier><identifier>DOI: 10.1007/s10120-016-0669-2</identifier><identifier>PMID: 27858181</identifier><language>eng</language><publisher>Tokyo: Springer Japan</publisher><subject>Abdominal Surgery ; Adult ; Aged ; Aged, 80 and over ; Cancer ; Cancer Research ; Cancer-Associated Fibroblasts - pathology ; Carcinoma ; Carcinoma, Signet Ring Cell - mortality ; Carcinoma, Signet Ring Cell - pathology ; Cell migration ; Disease-Free Survival ; Female ; Fibroblasts ; Gastric cancer ; Gastroenterology ; Humans ; Kaplan-Meier Estimate ; Male ; Medicine ; Medicine & Public Health ; Mesenchyme ; Metastases ; Middle Aged ; Multivariate analysis ; Oncology ; Original Article ; Phenotype ; Prognosis ; Ribonucleic acid ; RNA ; Src protein ; Stomach Neoplasms - mortality ; Stomach Neoplasms - pathology ; Stroma ; Surgical Oncology ; Survival ; Tumor Microenvironment ; Young Adult</subject><ispartof>Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2017-07, Vol.20 (4), p.591-601</ispartof><rights>The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2016</rights><rights>Gastric Cancer is a copyright of Springer, 2017.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c532t-76a48eb27014cabc122bade32ec1433b3dce0987c42e647944e7ff6bf946a7243</citedby><cites>FETCH-LOGICAL-c532t-76a48eb27014cabc122bade32ec1433b3dce0987c42e647944e7ff6bf946a7243</cites><orcidid>0000-0002-5435-5363</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10120-016-0669-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10120-016-0669-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27858181$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Dakeun</creatorcontrib><creatorcontrib>Ham, In-Hye</creatorcontrib><creatorcontrib>Son, Sang Yong</creatorcontrib><creatorcontrib>Han, Sang-Uk</creatorcontrib><creatorcontrib>Kim, Young-Bae</creatorcontrib><creatorcontrib>Hur, Hoon</creatorcontrib><title>Intratumor stromal proportion predicts aggressive phenotype of gastric signet ring cell carcinomas</title><title>Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association</title><addtitle>Gastric Cancer</addtitle><addtitle>Gastric Cancer</addtitle><description>Objective
The aim of this study was to evaluate the prognostic significance of the intratumor stromal proportion in gastric signet ring cell (SRC) carcinomas.
Background
Cancer stroma, as exemplified by cancer-associated fibroblasts (CAFs), plays critical roles in cancer proliferation, invasion, and metastasis.
Methods
One hundred seventy-five SRC carcinoma cases were classified according to the intratumor desmoplastic stromal proportion to then analyze the clinicopathologic characteristics of stroma-rich cases. We also investigated the impact of CAFs on the migration as well as on the phenotypic changes of gastric SRC carcinomas in vitro. Furthermore, we performed RNA sequencing of a pair of CAFs and normal-tissue-associated fibroblasts.
Results
Stroma-rich SRC carcinomas (64 of 175 cases, 36.5%) were associated with female patients (
P
= 0.045), large tumor size (
P
= 0.007), higher T category (
P
< 0.001), and the presence of perineural invasion (
P
= 0.018). Patients with stroma-rich SRC carcinomas had a significantly shorter disease-free survival (
P
< 0.001) and overall survival (
P
< 0.001). However, in a subgroup analysis, the prognostic significance of the stromal proportion correlated only with patients with T3/4 disease. From multivariate analysis, the high stromal proportion is an independent prognostic factor to predict worse disease-free survival (hazard ratio 2.288;
P
= 0.001) and overall survival (hazard ratio 2.503;
P
= 0.001). We found that CAFs enhanced the migratory abilities of cancer cells through the epithelial–mesenchymal transition, and RNA sequencing results confirmed these findings.
Conclusions
The intratumor stromal proportion could be a useful prognostic biomarker and a potential therapeutic target in gastric SRC carcinomas.</description><subject>Abdominal Surgery</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>Cancer-Associated Fibroblasts - pathology</subject><subject>Carcinoma</subject><subject>Carcinoma, Signet Ring Cell - mortality</subject><subject>Carcinoma, Signet Ring Cell - pathology</subject><subject>Cell migration</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Fibroblasts</subject><subject>Gastric cancer</subject><subject>Gastroenterology</subject><subject>Humans</subject><subject>Kaplan-Meier Estimate</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mesenchyme</subject><subject>Metastases</subject><subject>Middle Aged</subject><subject>Multivariate analysis</subject><subject>Oncology</subject><subject>Original Article</subject><subject>Phenotype</subject><subject>Prognosis</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Src protein</subject><subject>Stomach Neoplasms - mortality</subject><subject>Stomach Neoplasms - pathology</subject><subject>Stroma</subject><subject>Surgical Oncology</subject><subject>Survival</subject><subject>Tumor Microenvironment</subject><subject>Young Adult</subject><issn>1436-3291</issn><issn>1436-3305</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kUFP3DAQhS1UBMvCD-gFWeqllxSP49jJESEKK63UC5wtxztJjTZxsB0k_n0dLSCE1JPn8N7nN_MI-Q7sFzCmriIw4KxgIAsmZVPwI7ICUcqiLFn17X3mDZySsxifGIOqAXlCTrmqqxpqWJF2M6Zg0jz4QGMKfjB7OgU_-ZCcH_OIO2dTpKbvA8boXpBOf3H06XVC6jvam-xylkbXj5hocGNPLe731Jpg3Zh58Zwcd2Yf8eLtXZPH37cPN_fF9s_d5uZ6W9iq5KlQ0ogaW64YCGtaC5y3ZoclR5v3KNtyZ5E1tbKCoxSqEQJV18m2a4Q0iotyTX4euDn_84wx6cHFJYsZ0c9RQy2gZkIwyNIfX6RPfg5jTqehAS5qVbEFCAeVDT7GgJ2eghtMeNXA9FKAPhSgcwF6KUDz7Ll8I8_tgLsPx_vFs4AfBHFajoXh09f_pf4DsraRyg</recordid><startdate>20170701</startdate><enddate>20170701</enddate><creator>Lee, Dakeun</creator><creator>Ham, In-Hye</creator><creator>Son, Sang Yong</creator><creator>Han, Sang-Uk</creator><creator>Kim, Young-Bae</creator><creator>Hur, Hoon</creator><general>Springer Japan</general><general>Springer Nature B.V</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>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-5435-5363</orcidid></search><sort><creationdate>20170701</creationdate><title>Intratumor stromal proportion predicts aggressive phenotype of gastric signet ring cell carcinomas</title><author>Lee, Dakeun ; Ham, In-Hye ; Son, Sang Yong ; Han, Sang-Uk ; Kim, Young-Bae ; Hur, Hoon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c532t-76a48eb27014cabc122bade32ec1433b3dce0987c42e647944e7ff6bf946a7243</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Abdominal Surgery</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Cancer</topic><topic>Cancer Research</topic><topic>Cancer-Associated Fibroblasts - pathology</topic><topic>Carcinoma</topic><topic>Carcinoma, Signet Ring Cell - mortality</topic><topic>Carcinoma, Signet Ring Cell - pathology</topic><topic>Cell migration</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Fibroblasts</topic><topic>Gastric cancer</topic><topic>Gastroenterology</topic><topic>Humans</topic><topic>Kaplan-Meier Estimate</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mesenchyme</topic><topic>Metastases</topic><topic>Middle Aged</topic><topic>Multivariate analysis</topic><topic>Oncology</topic><topic>Original Article</topic><topic>Phenotype</topic><topic>Prognosis</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Src protein</topic><topic>Stomach Neoplasms - mortality</topic><topic>Stomach Neoplasms - pathology</topic><topic>Stroma</topic><topic>Surgical Oncology</topic><topic>Survival</topic><topic>Tumor Microenvironment</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Dakeun</creatorcontrib><creatorcontrib>Ham, In-Hye</creatorcontrib><creatorcontrib>Son, Sang Yong</creatorcontrib><creatorcontrib>Han, Sang-Uk</creatorcontrib><creatorcontrib>Kim, Young-Bae</creatorcontrib><creatorcontrib>Hur, Hoon</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Dakeun</au><au>Ham, In-Hye</au><au>Son, Sang Yong</au><au>Han, Sang-Uk</au><au>Kim, Young-Bae</au><au>Hur, Hoon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intratumor stromal proportion predicts aggressive phenotype of gastric signet ring cell carcinomas</atitle><jtitle>Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association</jtitle><stitle>Gastric Cancer</stitle><addtitle>Gastric Cancer</addtitle><date>2017-07-01</date><risdate>2017</risdate><volume>20</volume><issue>4</issue><spage>591</spage><epage>601</epage><pages>591-601</pages><issn>1436-3291</issn><eissn>1436-3305</eissn><abstract>Objective
The aim of this study was to evaluate the prognostic significance of the intratumor stromal proportion in gastric signet ring cell (SRC) carcinomas.
Background
Cancer stroma, as exemplified by cancer-associated fibroblasts (CAFs), plays critical roles in cancer proliferation, invasion, and metastasis.
Methods
One hundred seventy-five SRC carcinoma cases were classified according to the intratumor desmoplastic stromal proportion to then analyze the clinicopathologic characteristics of stroma-rich cases. We also investigated the impact of CAFs on the migration as well as on the phenotypic changes of gastric SRC carcinomas in vitro. Furthermore, we performed RNA sequencing of a pair of CAFs and normal-tissue-associated fibroblasts.
Results
Stroma-rich SRC carcinomas (64 of 175 cases, 36.5%) were associated with female patients (
P
= 0.045), large tumor size (
P
= 0.007), higher T category (
P
< 0.001), and the presence of perineural invasion (
P
= 0.018). Patients with stroma-rich SRC carcinomas had a significantly shorter disease-free survival (
P
< 0.001) and overall survival (
P
< 0.001). However, in a subgroup analysis, the prognostic significance of the stromal proportion correlated only with patients with T3/4 disease. From multivariate analysis, the high stromal proportion is an independent prognostic factor to predict worse disease-free survival (hazard ratio 2.288;
P
= 0.001) and overall survival (hazard ratio 2.503;
P
= 0.001). We found that CAFs enhanced the migratory abilities of cancer cells through the epithelial–mesenchymal transition, and RNA sequencing results confirmed these findings.
Conclusions
The intratumor stromal proportion could be a useful prognostic biomarker and a potential therapeutic target in gastric SRC carcinomas.</abstract><cop>Tokyo</cop><pub>Springer Japan</pub><pmid>27858181</pmid><doi>10.1007/s10120-016-0669-2</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-5435-5363</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SpringerLink Journals - AutoHoldings |
| subjects | Abdominal Surgery Adult Aged Aged, 80 and over Cancer Cancer Research Cancer-Associated Fibroblasts - pathology Carcinoma Carcinoma, Signet Ring Cell - mortality Carcinoma, Signet Ring Cell - pathology Cell migration Disease-Free Survival Female Fibroblasts Gastric cancer Gastroenterology Humans Kaplan-Meier Estimate Male Medicine Medicine & Public Health Mesenchyme Metastases Middle Aged Multivariate analysis Oncology Original Article Phenotype Prognosis Ribonucleic acid RNA Src protein Stomach Neoplasms - mortality Stomach Neoplasms - pathology Stroma Surgical Oncology Survival Tumor Microenvironment Young Adult |
| title | Intratumor stromal proportion predicts aggressive phenotype of gastric signet ring cell carcinomas |
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