PD-L1 expression combined with microsatellite instability/CD8+ tumor infiltrating lymphocytes as a useful prognostic biomarker in gastric cancer
While the importance of programmed death-ligand 1 (PD-L1), mutation burden caused by microsatellite instability (MSI), and CD8+ tumor infiltrating lymphocytes (TILs) has become evident, the significance of PD-L1 expression on prognosis still remains controversial. We evaluated the usefulness of comb...
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| creator | Morihiro, Toshiaki Kuroda, Shinji Kanaya, Nobuhiko Kakiuchi, Yoshihiko Kubota, Tetsushi Aoyama, Katsuyuki Tanaka, Takehiro Kikuchi, Satoru Nagasaka, Takeshi Nishizaki, Masahiko Kagawa, Shunsuke Tazawa, Hiroshi Fujiwara, Toshiyoshi |
| description | While the importance of programmed death-ligand 1 (PD-L1), mutation burden caused by microsatellite instability (MSI), and CD8+ tumor infiltrating lymphocytes (TILs) has become evident, the significance of PD-L1 expression on prognosis still remains controversial. We evaluated the usefulness of combined markers of PD-L1 and MSI or CD8+ TILs as a prognostic biomarker in gastric cancer. A total of 283 patients with gastric cancer were reviewed retrospectively. PD-L1 expression on >5% tumor cells was defined as PD-L1-positive. PD-L1-positive rate was 15.5% (44/283). PD-L1 positivity was significantly correlated with invasive and advanced cancer and also significantly correlated with MSI, whereas no significance was observed with CD8+ TILs. Kaplan–Meier analysis showed that PD-L1 positivity significantly correlated with a poor prognosis (p = 0.0025). Multivariate analysis revealed that PD-L1 positivity was an independent poor prognostic factor (hazard ratio [HR]: 1.97, p = 0.0106) along with diffuse histological type and lymph node metastases. Combinations of PD-L1 and MSI (HR: 2.18) or CD8+ TILs (HR: 2.57) were stronger predictive factors for prognosis than PD-L1 alone. In conclusion, combined markers of PD-L1 and MSI or CD8+ TILs may be more useful prognostic biomarkers in gastric cancer, and better clarify the immune status of gastric cancer patients. |
| doi_str_mv | 10.1038/s41598-019-41177-2 |
| format | Article |
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We evaluated the usefulness of combined markers of PD-L1 and MSI or CD8+ TILs as a prognostic biomarker in gastric cancer. A total of 283 patients with gastric cancer were reviewed retrospectively. PD-L1 expression on >5% tumor cells was defined as PD-L1-positive. PD-L1-positive rate was 15.5% (44/283). PD-L1 positivity was significantly correlated with invasive and advanced cancer and also significantly correlated with MSI, whereas no significance was observed with CD8+ TILs. Kaplan–Meier analysis showed that PD-L1 positivity significantly correlated with a poor prognosis (p = 0.0025). Multivariate analysis revealed that PD-L1 positivity was an independent poor prognostic factor (hazard ratio [HR]: 1.97, p = 0.0106) along with diffuse histological type and lymph node metastases. Combinations of PD-L1 and MSI (HR: 2.18) or CD8+ TILs (HR: 2.57) were stronger predictive factors for prognosis than PD-L1 alone. In conclusion, combined markers of PD-L1 and MSI or CD8+ TILs may be more useful prognostic biomarkers in gastric cancer, and better clarify the immune status of gastric cancer patients.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-019-41177-2</identifier><identifier>PMID: 30874607</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/67/1504/1829 ; 631/67/580 ; 82/51 ; Adult ; Aged ; Aged, 80 and over ; Apoptosis ; B7-H1 Antigen - genetics ; B7-H1 Antigen - metabolism ; Biomarkers ; Biomarkers, Tumor - blood ; CD8 antigen ; CD8-Positive T-Lymphocytes - immunology ; Disease-Free Survival ; Female ; Gastric cancer ; Humanities and Social Sciences ; Humans ; Immune status ; Invasiveness ; Kaplan-Meier Estimate ; Lymph nodes ; Lymphatic Metastasis - pathology ; Lymphocytes ; Lymphocytes, Tumor-Infiltrating - immunology ; Male ; Metastases ; Microsatellite Instability ; Microsatellite Repeats - genetics ; Middle Aged ; multidisciplinary ; Multivariate analysis ; PD-L1 protein ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Science ; Science (multidisciplinary) ; Stomach Neoplasms - genetics ; Stomach Neoplasms - immunology ; Tumor cells</subject><ispartof>Scientific reports, 2019-03, Vol.9 (1), p.4633-4633, Article 4633</ispartof><rights>The Author(s) 2019</rights><rights>This work is published under http://creativecommons.org/licenses/by/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-c518t-f7a40cf9f1c260758583a59836f221a5b01e9be57ed125c4f2d4c9140c557d423</citedby><cites>FETCH-LOGICAL-c518t-f7a40cf9f1c260758583a59836f221a5b01e9be57ed125c4f2d4c9140c557d423</cites><orcidid>0000-0003-4658-1050</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420501/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420501/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30874607$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Morihiro, Toshiaki</creatorcontrib><creatorcontrib>Kuroda, Shinji</creatorcontrib><creatorcontrib>Kanaya, Nobuhiko</creatorcontrib><creatorcontrib>Kakiuchi, Yoshihiko</creatorcontrib><creatorcontrib>Kubota, Tetsushi</creatorcontrib><creatorcontrib>Aoyama, Katsuyuki</creatorcontrib><creatorcontrib>Tanaka, Takehiro</creatorcontrib><creatorcontrib>Kikuchi, Satoru</creatorcontrib><creatorcontrib>Nagasaka, Takeshi</creatorcontrib><creatorcontrib>Nishizaki, Masahiko</creatorcontrib><creatorcontrib>Kagawa, Shunsuke</creatorcontrib><creatorcontrib>Tazawa, Hiroshi</creatorcontrib><creatorcontrib>Fujiwara, Toshiyoshi</creatorcontrib><title>PD-L1 expression combined with microsatellite instability/CD8+ tumor infiltrating lymphocytes as a useful prognostic biomarker in gastric cancer</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>While the importance of programmed death-ligand 1 (PD-L1), mutation burden caused by microsatellite instability (MSI), and CD8+ tumor infiltrating lymphocytes (TILs) has become evident, the significance of PD-L1 expression on prognosis still remains controversial. We evaluated the usefulness of combined markers of PD-L1 and MSI or CD8+ TILs as a prognostic biomarker in gastric cancer. A total of 283 patients with gastric cancer were reviewed retrospectively. PD-L1 expression on >5% tumor cells was defined as PD-L1-positive. PD-L1-positive rate was 15.5% (44/283). PD-L1 positivity was significantly correlated with invasive and advanced cancer and also significantly correlated with MSI, whereas no significance was observed with CD8+ TILs. Kaplan–Meier analysis showed that PD-L1 positivity significantly correlated with a poor prognosis (p = 0.0025). Multivariate analysis revealed that PD-L1 positivity was an independent poor prognostic factor (hazard ratio [HR]: 1.97, p = 0.0106) along with diffuse histological type and lymph node metastases. Combinations of PD-L1 and MSI (HR: 2.18) or CD8+ TILs (HR: 2.57) were stronger predictive factors for prognosis than PD-L1 alone. In conclusion, combined markers of PD-L1 and MSI or CD8+ TILs may be more useful prognostic biomarkers in gastric cancer, and better clarify the immune status of gastric cancer patients.</description><subject>631/67/1504/1829</subject><subject>631/67/580</subject><subject>82/51</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Apoptosis</subject><subject>B7-H1 Antigen - genetics</subject><subject>B7-H1 Antigen - metabolism</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - blood</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Gastric cancer</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Immune status</subject><subject>Invasiveness</subject><subject>Kaplan-Meier Estimate</subject><subject>Lymph nodes</subject><subject>Lymphatic Metastasis - pathology</subject><subject>Lymphocytes</subject><subject>Lymphocytes, Tumor-Infiltrating - 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genetics</topic><topic>B7-H1 Antigen - metabolism</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - blood</topic><topic>CD8 antigen</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Gastric cancer</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Immune status</topic><topic>Invasiveness</topic><topic>Kaplan-Meier Estimate</topic><topic>Lymph nodes</topic><topic>Lymphatic Metastasis - pathology</topic><topic>Lymphocytes</topic><topic>Lymphocytes, Tumor-Infiltrating - immunology</topic><topic>Male</topic><topic>Metastases</topic><topic>Microsatellite Instability</topic><topic>Microsatellite Repeats - genetics</topic><topic>Middle Aged</topic><topic>multidisciplinary</topic><topic>Multivariate analysis</topic><topic>PD-L1 protein</topic><topic>Prognosis</topic><topic>Proportional Hazards Models</topic><topic>Retrospective Studies</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Stomach Neoplasms - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Morihiro, Toshiaki</au><au>Kuroda, Shinji</au><au>Kanaya, Nobuhiko</au><au>Kakiuchi, Yoshihiko</au><au>Kubota, Tetsushi</au><au>Aoyama, Katsuyuki</au><au>Tanaka, Takehiro</au><au>Kikuchi, Satoru</au><au>Nagasaka, Takeshi</au><au>Nishizaki, Masahiko</au><au>Kagawa, Shunsuke</au><au>Tazawa, Hiroshi</au><au>Fujiwara, Toshiyoshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PD-L1 expression combined with microsatellite instability/CD8+ tumor infiltrating lymphocytes as a useful prognostic biomarker in gastric cancer</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2019-03-15</date><risdate>2019</risdate><volume>9</volume><issue>1</issue><spage>4633</spage><epage>4633</epage><pages>4633-4633</pages><artnum>4633</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>While the importance of programmed death-ligand 1 (PD-L1), mutation burden caused by microsatellite instability (MSI), and CD8+ tumor infiltrating lymphocytes (TILs) has become evident, the significance of PD-L1 expression on prognosis still remains controversial. We evaluated the usefulness of combined markers of PD-L1 and MSI or CD8+ TILs as a prognostic biomarker in gastric cancer. A total of 283 patients with gastric cancer were reviewed retrospectively. PD-L1 expression on >5% tumor cells was defined as PD-L1-positive. PD-L1-positive rate was 15.5% (44/283). PD-L1 positivity was significantly correlated with invasive and advanced cancer and also significantly correlated with MSI, whereas no significance was observed with CD8+ TILs. Kaplan–Meier analysis showed that PD-L1 positivity significantly correlated with a poor prognosis (p = 0.0025). Multivariate analysis revealed that PD-L1 positivity was an independent poor prognostic factor (hazard ratio [HR]: 1.97, p = 0.0106) along with diffuse histological type and lymph node metastases. Combinations of PD-L1 and MSI (HR: 2.18) or CD8+ TILs (HR: 2.57) were stronger predictive factors for prognosis than PD-L1 alone. In conclusion, combined markers of PD-L1 and MSI or CD8+ TILs may be more useful prognostic biomarkers in gastric cancer, and better clarify the immune status of gastric cancer patients.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30874607</pmid><doi>10.1038/s41598-019-41177-2</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-4658-1050</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 631/67/1504/1829 631/67/580 82/51 Adult Aged Aged, 80 and over Apoptosis B7-H1 Antigen - genetics B7-H1 Antigen - metabolism Biomarkers Biomarkers, Tumor - blood CD8 antigen CD8-Positive T-Lymphocytes - immunology Disease-Free Survival Female Gastric cancer Humanities and Social Sciences Humans Immune status Invasiveness Kaplan-Meier Estimate Lymph nodes Lymphatic Metastasis - pathology Lymphocytes Lymphocytes, Tumor-Infiltrating - immunology Male Metastases Microsatellite Instability Microsatellite Repeats - genetics Middle Aged multidisciplinary Multivariate analysis PD-L1 protein Prognosis Proportional Hazards Models Retrospective Studies Science Science (multidisciplinary) Stomach Neoplasms - genetics Stomach Neoplasms - immunology Tumor cells |
| title | PD-L1 expression combined with microsatellite instability/CD8+ tumor infiltrating lymphocytes as a useful prognostic biomarker in gastric cancer |
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