Prognostic Impact of Immune-Related Gene Expression in Preoperative Peripheral Blood from Gastric Cancer Patients

Background Anti-PD-1 therapy has shown a promising clinical outcome in gastric cancer (GC). We evaluated the clinical significance of systemic immune-related gene expression in GC patients who underwent surgery. Methods The correlation between the preoperative PD - 1 , PD - L1, and CD8 mRNA levels i...

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Veröffentlicht in:Annals of surgical oncology 2018-11, Vol.25 (12), p.3755-3763
Hauptverfasser: Ito, Shuhei, Fukagawa, Takeo, Noda, Miwa, Hu, Qingjiang, Nambara, Sho, Shimizu, Dai, Kuroda, Yosuke, Eguchi, Hidetoshi, Masuda, Takaaki, Sato, Tetsuya, Katai, Hitoshi, Sasako, Mitsuru, Mimori, Koshi
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container_end_page 3763
container_issue 12
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container_title Annals of surgical oncology
container_volume 25
creator Ito, Shuhei
Fukagawa, Takeo
Noda, Miwa
Hu, Qingjiang
Nambara, Sho
Shimizu, Dai
Kuroda, Yosuke
Eguchi, Hidetoshi
Masuda, Takaaki
Sato, Tetsuya
Katai, Hitoshi
Sasako, Mitsuru
Mimori, Koshi
description Background Anti-PD-1 therapy has shown a promising clinical outcome in gastric cancer (GC). We evaluated the clinical significance of systemic immune-related gene expression in GC patients who underwent surgery. Methods The correlation between the preoperative PD - 1 , PD - L1, and CD8 mRNA levels in peripheral blood (PB) and clinicopathological factors, including survival, in 372 GC patients was evaluated using quantitative RT-PCR. PD-1- and PD-L1-expressing cells were identified by flow cytometric analysis. Results The PD - 1 , PD - L1, and CD8 mRNA levels in GC patients were significantly higher than those in normal controls, respectively (all P  
doi_str_mv 10.1245/s10434-018-6739-4
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We evaluated the clinical significance of systemic immune-related gene expression in GC patients who underwent surgery. Methods The correlation between the preoperative PD - 1 , PD - L1, and CD8 mRNA levels in peripheral blood (PB) and clinicopathological factors, including survival, in 372 GC patients was evaluated using quantitative RT-PCR. PD-1- and PD-L1-expressing cells were identified by flow cytometric analysis. Results The PD - 1 , PD - L1, and CD8 mRNA levels in GC patients were significantly higher than those in normal controls, respectively (all P  < 0.0001). The levels of each gene were positively correlated with those of the other two genes (all P  < 0.0001). GC patients with low PD - 1, high PD - L1, and low CD8 mRNA levels had significantly poorer overall survival (OS) than those with high PD - 1 , low PD - L1, and high CD8 mRNA levels, respectively ( P  < 0.01, P  < 0.05, and P  < 0.05, respectively). Multivariate analysis showed that low PD - 1 and high PD - L1 mRNA levels were independent poor prognostic factors for OS ( PD - 1 : HR 2.38, 95% CI 1.27–4.78, P  < 0.01; PD - L1 : HR 1.81, 95% CI 1.15–2.78, P  < 0.05). PD-1 and PD-L1 expression occurred on T cells (> 90%) and T cells or monocytes (> 70%), respectively. Conclusions The PD - 1 , PD - L1 , and CD8 mRNA levels in preoperative PB reflected the anti-tumour immune response, and the low PD - 1 and high PD - L1 mRNA levels in PB were independent poor prognostic markers in GC patients who underwent surgery.]]></description><identifier>ISSN: 1068-9265</identifier><identifier>EISSN: 1534-4681</identifier><identifier>DOI: 10.1245/s10434-018-6739-4</identifier><identifier>PMID: 30203407</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>B7-H1 Antigen - genetics ; Biomarkers, Tumor - genetics ; Case-Control Studies ; CD8 Antigens - genetics ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Medicine ; Medicine &amp; Public Health ; Neoplasm Invasiveness ; Oncology ; Prognosis ; Programmed Cell Death 1 Receptor - genetics ; Stomach Neoplasms - genetics ; Stomach Neoplasms - pathology ; Stomach Neoplasms - surgery ; Surgery ; Surgical Oncology ; Survival Rate ; Translational Research and Biomarkers</subject><ispartof>Annals of surgical oncology, 2018-11, Vol.25 (12), p.3755-3763</ispartof><rights>Society of Surgical Oncology 2018</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c410t-d1ae000a6d542364bad688ce61754c2eed1b4c934228dd880d1577c32c38d1403</citedby><cites>FETCH-LOGICAL-c410t-d1ae000a6d542364bad688ce61754c2eed1b4c934228dd880d1577c32c38d1403</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1245/s10434-018-6739-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1245/s10434-018-6739-4$$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/30203407$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ito, Shuhei</creatorcontrib><creatorcontrib>Fukagawa, Takeo</creatorcontrib><creatorcontrib>Noda, Miwa</creatorcontrib><creatorcontrib>Hu, Qingjiang</creatorcontrib><creatorcontrib>Nambara, Sho</creatorcontrib><creatorcontrib>Shimizu, Dai</creatorcontrib><creatorcontrib>Kuroda, Yosuke</creatorcontrib><creatorcontrib>Eguchi, Hidetoshi</creatorcontrib><creatorcontrib>Masuda, Takaaki</creatorcontrib><creatorcontrib>Sato, Tetsuya</creatorcontrib><creatorcontrib>Katai, Hitoshi</creatorcontrib><creatorcontrib>Sasako, Mitsuru</creatorcontrib><creatorcontrib>Mimori, Koshi</creatorcontrib><title>Prognostic Impact of Immune-Related Gene Expression in Preoperative Peripheral Blood from Gastric Cancer Patients</title><title>Annals of surgical oncology</title><addtitle>Ann Surg Oncol</addtitle><addtitle>Ann Surg Oncol</addtitle><description><![CDATA[Background Anti-PD-1 therapy has shown a promising clinical outcome in gastric cancer (GC). We evaluated the clinical significance of systemic immune-related gene expression in GC patients who underwent surgery. Methods The correlation between the preoperative PD - 1 , PD - L1, and CD8 mRNA levels in peripheral blood (PB) and clinicopathological factors, including survival, in 372 GC patients was evaluated using quantitative RT-PCR. PD-1- and PD-L1-expressing cells were identified by flow cytometric analysis. Results The PD - 1 , PD - L1, and CD8 mRNA levels in GC patients were significantly higher than those in normal controls, respectively (all P  < 0.0001). The levels of each gene were positively correlated with those of the other two genes (all P  < 0.0001). GC patients with low PD - 1, high PD - L1, and low CD8 mRNA levels had significantly poorer overall survival (OS) than those with high PD - 1 , low PD - L1, and high CD8 mRNA levels, respectively ( P  < 0.01, P  < 0.05, and P  < 0.05, respectively). Multivariate analysis showed that low PD - 1 and high PD - L1 mRNA levels were independent poor prognostic factors for OS ( PD - 1 : HR 2.38, 95% CI 1.27–4.78, P  < 0.01; PD - L1 : HR 1.81, 95% CI 1.15–2.78, P  < 0.05). PD-1 and PD-L1 expression occurred on T cells (> 90%) and T cells or monocytes (> 70%), respectively. Conclusions The PD - 1 , PD - L1 , and CD8 mRNA levels in preoperative PB reflected the anti-tumour immune response, and the low PD - 1 and high PD - L1 mRNA levels in PB were independent poor prognostic markers in GC patients who underwent surgery.]]></description><subject>B7-H1 Antigen - genetics</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Case-Control Studies</subject><subject>CD8 Antigens - genetics</subject><subject>Follow-Up Studies</subject><subject>Humans</subject><subject>Lymphatic Metastasis</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Neoplasm Invasiveness</subject><subject>Oncology</subject><subject>Prognosis</subject><subject>Programmed Cell Death 1 Receptor - genetics</subject><subject>Stomach Neoplasms - genetics</subject><subject>Stomach Neoplasms - pathology</subject><subject>Stomach Neoplasms - surgery</subject><subject>Surgery</subject><subject>Surgical Oncology</subject><subject>Survival Rate</subject><subject>Translational Research and Biomarkers</subject><issn>1068-9265</issn><issn>1534-4681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtOwzAQRS0E4v0BbJCXbALjRxJ3CRWUSkhUCNaWa09LUGIHO0Hw97gqsGQ1M_aZK80h5IzBJeOyvEoMpJAFMFVUtZgUcoccsjK_yEqx3dxDpYoJr8oDcpTSGwCrBZT75EAAByGhPiTvixjWPqShsXTe9cYONKxy140eiydszYCOztAjvf3sI6bUBE8bTxcRQ4_RDM0H0gXGpn_NU0tv2hAcXcXQ0ZlJQ8yxU-MtRrrILPohnZC9lWkTnv7UY_Jyd_s8vS8eHmfz6fVDYSWDoXDMIACYypWSi0oujauUslixupSWIzq2lHYiJOfKOaXAsbKureBWKMckiGNysc3tY3gfMQ26a5LFtjUew5g0Z8AFB17zjLItamNIKeJK97HpTPzSDPTGtN6a1tm03pjWMu-c_8SPyw7d38av2gzwLZDyl19j1G9hjD6f_E_qNyWeiV4</recordid><startdate>20181101</startdate><enddate>20181101</enddate><creator>Ito, Shuhei</creator><creator>Fukagawa, Takeo</creator><creator>Noda, Miwa</creator><creator>Hu, Qingjiang</creator><creator>Nambara, Sho</creator><creator>Shimizu, Dai</creator><creator>Kuroda, Yosuke</creator><creator>Eguchi, Hidetoshi</creator><creator>Masuda, Takaaki</creator><creator>Sato, Tetsuya</creator><creator>Katai, Hitoshi</creator><creator>Sasako, Mitsuru</creator><creator>Mimori, Koshi</creator><general>Springer International Publishing</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></search><sort><creationdate>20181101</creationdate><title>Prognostic Impact of Immune-Related Gene Expression in Preoperative Peripheral Blood from Gastric Cancer Patients</title><author>Ito, Shuhei ; Fukagawa, Takeo ; Noda, Miwa ; Hu, Qingjiang ; Nambara, Sho ; Shimizu, Dai ; Kuroda, Yosuke ; Eguchi, Hidetoshi ; Masuda, Takaaki ; Sato, Tetsuya ; Katai, Hitoshi ; Sasako, Mitsuru ; Mimori, Koshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c410t-d1ae000a6d542364bad688ce61754c2eed1b4c934228dd880d1577c32c38d1403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>B7-H1 Antigen - genetics</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Case-Control Studies</topic><topic>CD8 Antigens - genetics</topic><topic>Follow-Up Studies</topic><topic>Humans</topic><topic>Lymphatic Metastasis</topic><topic>Medicine</topic><topic>Medicine &amp; Public Health</topic><topic>Neoplasm Invasiveness</topic><topic>Oncology</topic><topic>Prognosis</topic><topic>Programmed Cell Death 1 Receptor - genetics</topic><topic>Stomach Neoplasms - genetics</topic><topic>Stomach Neoplasms - pathology</topic><topic>Stomach Neoplasms - surgery</topic><topic>Surgery</topic><topic>Surgical Oncology</topic><topic>Survival Rate</topic><topic>Translational Research and Biomarkers</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ito, Shuhei</creatorcontrib><creatorcontrib>Fukagawa, Takeo</creatorcontrib><creatorcontrib>Noda, Miwa</creatorcontrib><creatorcontrib>Hu, Qingjiang</creatorcontrib><creatorcontrib>Nambara, Sho</creatorcontrib><creatorcontrib>Shimizu, Dai</creatorcontrib><creatorcontrib>Kuroda, Yosuke</creatorcontrib><creatorcontrib>Eguchi, Hidetoshi</creatorcontrib><creatorcontrib>Masuda, Takaaki</creatorcontrib><creatorcontrib>Sato, Tetsuya</creatorcontrib><creatorcontrib>Katai, Hitoshi</creatorcontrib><creatorcontrib>Sasako, Mitsuru</creatorcontrib><creatorcontrib>Mimori, Koshi</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>Annals of surgical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ito, Shuhei</au><au>Fukagawa, Takeo</au><au>Noda, Miwa</au><au>Hu, Qingjiang</au><au>Nambara, Sho</au><au>Shimizu, Dai</au><au>Kuroda, Yosuke</au><au>Eguchi, Hidetoshi</au><au>Masuda, Takaaki</au><au>Sato, Tetsuya</au><au>Katai, Hitoshi</au><au>Sasako, Mitsuru</au><au>Mimori, Koshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prognostic Impact of Immune-Related Gene Expression in Preoperative Peripheral Blood from Gastric Cancer Patients</atitle><jtitle>Annals of surgical oncology</jtitle><stitle>Ann Surg Oncol</stitle><addtitle>Ann Surg Oncol</addtitle><date>2018-11-01</date><risdate>2018</risdate><volume>25</volume><issue>12</issue><spage>3755</spage><epage>3763</epage><pages>3755-3763</pages><issn>1068-9265</issn><eissn>1534-4681</eissn><abstract><![CDATA[Background Anti-PD-1 therapy has shown a promising clinical outcome in gastric cancer (GC). We evaluated the clinical significance of systemic immune-related gene expression in GC patients who underwent surgery. Methods The correlation between the preoperative PD - 1 , PD - L1, and CD8 mRNA levels in peripheral blood (PB) and clinicopathological factors, including survival, in 372 GC patients was evaluated using quantitative RT-PCR. PD-1- and PD-L1-expressing cells were identified by flow cytometric analysis. Results The PD - 1 , PD - L1, and CD8 mRNA levels in GC patients were significantly higher than those in normal controls, respectively (all P  < 0.0001). The levels of each gene were positively correlated with those of the other two genes (all P  < 0.0001). GC patients with low PD - 1, high PD - L1, and low CD8 mRNA levels had significantly poorer overall survival (OS) than those with high PD - 1 , low PD - L1, and high CD8 mRNA levels, respectively ( P  < 0.01, P  < 0.05, and P  < 0.05, respectively). Multivariate analysis showed that low PD - 1 and high PD - L1 mRNA levels were independent poor prognostic factors for OS ( PD - 1 : HR 2.38, 95% CI 1.27–4.78, P  < 0.01; PD - L1 : HR 1.81, 95% CI 1.15–2.78, P  < 0.05). PD-1 and PD-L1 expression occurred on T cells (> 90%) and T cells or monocytes (> 70%), respectively. Conclusions The PD - 1 , PD - L1 , and CD8 mRNA levels in preoperative PB reflected the anti-tumour immune response, and the low PD - 1 and high PD - L1 mRNA levels in PB were independent poor prognostic markers in GC patients who underwent surgery.]]></abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>30203407</pmid><doi>10.1245/s10434-018-6739-4</doi><tpages>9</tpages></addata></record>
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subjects B7-H1 Antigen - genetics
Biomarkers, Tumor - genetics
Case-Control Studies
CD8 Antigens - genetics
Follow-Up Studies
Humans
Lymphatic Metastasis
Medicine
Medicine & Public Health
Neoplasm Invasiveness
Oncology
Prognosis
Programmed Cell Death 1 Receptor - genetics
Stomach Neoplasms - genetics
Stomach Neoplasms - pathology
Stomach Neoplasms - surgery
Surgery
Surgical Oncology
Survival Rate
Translational Research and Biomarkers
title Prognostic Impact of Immune-Related Gene Expression in Preoperative Peripheral Blood from Gastric Cancer Patients
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