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Association of PD-L1 expression and PD-L1 gene polymorphism with poor prognosis in lung adenocarcinoma and squamous cell carcinoma
Programmed cell death 1 receptor (PD-1)/programmed death-1 ligand-1 (PD-L1) interaction has been linked to tumor immune evasion. PD-L1 expression has been indicated in identifying non–small cell lung carcinoma (NSCLC) patients for treatment with anti–PD-1 or anti–PD-L1 therapy. The goal of this stud...
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Published in: | Human pathology 2017-10, Vol.68, p.103-111 |
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description | Programmed cell death 1 receptor (PD-1)/programmed death-1 ligand-1 (PD-L1) interaction has been linked to tumor immune evasion. PD-L1 expression has been indicated in identifying non–small cell lung carcinoma (NSCLC) patients for treatment with anti–PD-1 or anti–PD-L1 therapy. The goal of this study was to evaluate the clinicopathologic values of PD-L1 expression and single-nucleotide polymorphisms (SNPs) in the PD-L1 gene in lung adenocarcinoma (ADC) and squamous cell carcinoma (SqCC). The 147 NSCLC tissues consisted of 84 samples of ADC and 63 samples of SqCC. All tissue microarray paraffin blocks were used for PD-L1 immunohistochemical assays with 22C3, SP263, and SP142 clones. Three SNPs in the PD-L1 gene, rs4143815, rs822336, and rs822337, were genotyped using SNP pyrosequencing. The PD-L1 expression was significantly higher in SqCC than in ADC. Among ADCs, PD-L1 expression was significantly higher in papillary and solid types than in lepidic and acinar types. Statistical associations of the PD-L1 expression with a shorter disease-free survival outcome and lymph node metastasis in the ADCs were found but no associations in SqCCs. Among the three SNPs, the rs4143815 genotype CC was statistically associated with positive 22C3 PD-L1 labeling in NSCLCs. The rs4143815 genotype GG instead showed a trend of shorter survival outcomes but did not reach statistical significance in the ADCs. Our results showed a significantly higher prevalence of positive PD-L1 expression in lung SqCC than in ADC. However, the PD-L1 expression and rs4143815 genotype GG might be useful for the prediction of poor prognosis in lung ADC cases.
•147 cases of non–small cell lung carcinoma were studied.•Positive PD-L1 expression was associated with poor prognosis in adenocarcinoma.•The rs4143815 genotype GG showed a trend of poor prognosis in adenocarcinoma.•The rs4143815 genotype CC was associated with PD-L1 expression. |
doi_str_mv | 10.1016/j.humpath.2017.08.016 |
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•147 cases of non–small cell lung carcinoma were studied.•Positive PD-L1 expression was associated with poor prognosis in adenocarcinoma.•The rs4143815 genotype GG showed a trend of poor prognosis in adenocarcinoma.•The rs4143815 genotype CC was associated with PD-L1 expression.</description><identifier>ISSN: 0046-8177</identifier><identifier>EISSN: 1532-8392</identifier><identifier>DOI: 10.1016/j.humpath.2017.08.016</identifier><identifier>PMID: 28851662</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adenocarcinoma ; Adenocarcinoma - genetics ; Adenocarcinoma - immunology ; Adenocarcinoma - secondary ; Adenocarcinoma - surgery ; Adenocarcinoma of Lung ; Adult ; Aged ; Aged, 80 and over ; Apoptosis ; B7-H1 Antigen - analysis ; B7-H1 Antigen - genetics ; Biomarkers, Tumor - analysis ; Biomarkers, Tumor - genetics ; Cancer therapies ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - immunology ; Carcinoma, Non-Small-Cell Lung - secondary ; Carcinoma, Non-Small-Cell Lung - surgery ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - immunology ; Carcinoma, Squamous Cell - secondary ; Carcinoma, Squamous Cell - surgery ; Cell death ; Cloning ; Deoxyribonucleic acid ; Disease-Free Survival ; DNA ; Female ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; Homozygote ; Hospitals ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Ligands ; Lung cancer ; Lung Neoplasms - genetics ; Lung Neoplasms - immunology ; Lung Neoplasms - pathology ; Lung Neoplasms - surgery ; Lymphatic Metastasis ; Male ; Medical prognosis ; Middle Aged ; Non–small cell lung carcinoma ; Phenotype ; Polymorphism, Single Nucleotide ; Programmed cell death 1 receptor ; Programmed death-1 ligand-1 ; Proportional Hazards Models ; Protein expression ; Proteins ; Retrospective Studies ; Single-nucleotide polymorphism ; Squamous cell carcinoma ; Survival analysis ; Time Factors ; Tissue Array Analysis</subject><ispartof>Human pathology, 2017-10, Vol.68, p.103-111</ispartof><rights>2017 Elsevier Inc.</rights><rights>Copyright © 2017 Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Oct 1, 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c393t-84acce1929ef316c861e16effbe5bc53dabf194ef627bb53be49aebb1984c7533</citedby><cites>FETCH-LOGICAL-c393t-84acce1929ef316c861e16effbe5bc53dabf194ef627bb53be49aebb1984c7533</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28851662$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yeo, Min-Kyung</creatorcontrib><creatorcontrib>Choi, Song-Yi</creatorcontrib><creatorcontrib>Seong, In-Ock</creatorcontrib><creatorcontrib>Suh, Kwang-Sun</creatorcontrib><creatorcontrib>Kim, Jin Man</creatorcontrib><creatorcontrib>Kim, Kyung-Hee</creatorcontrib><title>Association of PD-L1 expression and PD-L1 gene polymorphism with poor prognosis in lung adenocarcinoma and squamous cell carcinoma</title><title>Human pathology</title><addtitle>Hum Pathol</addtitle><description>Programmed cell death 1 receptor (PD-1)/programmed death-1 ligand-1 (PD-L1) interaction has been linked to tumor immune evasion. PD-L1 expression has been indicated in identifying non–small cell lung carcinoma (NSCLC) patients for treatment with anti–PD-1 or anti–PD-L1 therapy. The goal of this study was to evaluate the clinicopathologic values of PD-L1 expression and single-nucleotide polymorphisms (SNPs) in the PD-L1 gene in lung adenocarcinoma (ADC) and squamous cell carcinoma (SqCC). The 147 NSCLC tissues consisted of 84 samples of ADC and 63 samples of SqCC. All tissue microarray paraffin blocks were used for PD-L1 immunohistochemical assays with 22C3, SP263, and SP142 clones. Three SNPs in the PD-L1 gene, rs4143815, rs822336, and rs822337, were genotyped using SNP pyrosequencing. The PD-L1 expression was significantly higher in SqCC than in ADC. Among ADCs, PD-L1 expression was significantly higher in papillary and solid types than in lepidic and acinar types. Statistical associations of the PD-L1 expression with a shorter disease-free survival outcome and lymph node metastasis in the ADCs were found but no associations in SqCCs. Among the three SNPs, the rs4143815 genotype CC was statistically associated with positive 22C3 PD-L1 labeling in NSCLCs. The rs4143815 genotype GG instead showed a trend of shorter survival outcomes but did not reach statistical significance in the ADCs. Our results showed a significantly higher prevalence of positive PD-L1 expression in lung SqCC than in ADC. However, the PD-L1 expression and rs4143815 genotype GG might be useful for the prediction of poor prognosis in lung ADC cases.
•147 cases of non–small cell lung carcinoma were studied.•Positive PD-L1 expression was associated with poor prognosis in adenocarcinoma.•The rs4143815 genotype GG showed a trend of poor prognosis in adenocarcinoma.•The rs4143815 genotype CC was associated with PD-L1 expression.</description><subject>Adenocarcinoma</subject><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - immunology</subject><subject>Adenocarcinoma - secondary</subject><subject>Adenocarcinoma - surgery</subject><subject>Adenocarcinoma of Lung</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Apoptosis</subject><subject>B7-H1 Antigen - analysis</subject><subject>B7-H1 Antigen - genetics</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Cancer therapies</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - immunology</subject><subject>Carcinoma, Non-Small-Cell Lung - secondary</subject><subject>Carcinoma, Non-Small-Cell Lung - surgery</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - immunology</subject><subject>Carcinoma, Squamous Cell - secondary</subject><subject>Carcinoma, Squamous Cell - surgery</subject><subject>Cell death</subject><subject>Cloning</subject><subject>Deoxyribonucleic acid</subject><subject>Disease-Free Survival</subject><subject>DNA</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genetic Predisposition to Disease</subject><subject>Homozygote</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Kaplan-Meier Estimate</subject><subject>Ligands</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - immunology</subject><subject>Lung Neoplasms - pathology</subject><subject>Lung Neoplasms - surgery</subject><subject>Lymphatic Metastasis</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Middle Aged</subject><subject>Non–small cell lung carcinoma</subject><subject>Phenotype</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Programmed cell death 1 receptor</subject><subject>Programmed death-1 ligand-1</subject><subject>Proportional Hazards Models</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>Retrospective Studies</subject><subject>Single-nucleotide polymorphism</subject><subject>Squamous cell carcinoma</subject><subject>Survival analysis</subject><subject>Time Factors</subject><subject>Tissue Array Analysis</subject><issn>0046-8177</issn><issn>1532-8392</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNqFkU9v1DAQxS0EokvhI4AsceklwRPHTnxCVSl_pJXgAGfLcSa7XiV2aidAr3xyvOzSAxdOlp5_8-ZpHiEvgZXAQL45lPt1ms2yLysGTcnaMquPyAYEr4qWq-ox2TBWy6KFprkgz1I6MAYgavGUXFRtK0DKakN-XacUrDOLC56GgX55V2yB4s85YkpHzfj-LO7QI53DeD-FOO9dmugPt-yzEiKdY9j5kFyiztNx9TtqevTBmmidD5P5Y5PuVjOFNVGL40gf_p6TJ4MZE744v5fk2_vbrzcfi-3nD59urreF5YovRVsbaxFUpXDgIG0rAUHiMHQoOit4b7oBVI2DrJquE7zDWhnsOlBtbRvB-SW5OvnmsHcrpkVPLh2jGI85lQbFuap5DZDR1_-gh7BGn9NlSoqaK6mqTIkTZWNIKeKg5-gmE-81MH0sSR_0uSR9LEmzVmc1z706u6_dhP3D1N9WMvD2BGA-x3eHUSfr0FvsXUS76D64_6z4DRV4p7g</recordid><startdate>201710</startdate><enddate>201710</enddate><creator>Yeo, Min-Kyung</creator><creator>Choi, Song-Yi</creator><creator>Seong, In-Ock</creator><creator>Suh, Kwang-Sun</creator><creator>Kim, Jin Man</creator><creator>Kim, Kyung-Hee</creator><general>Elsevier Inc</general><general>Elsevier Limited</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>K9.</scope><scope>7X8</scope></search><sort><creationdate>201710</creationdate><title>Association of PD-L1 expression and PD-L1 gene polymorphism with poor prognosis in lung adenocarcinoma and squamous cell carcinoma</title><author>Yeo, Min-Kyung ; Choi, Song-Yi ; Seong, In-Ock ; Suh, Kwang-Sun ; Kim, Jin Man ; Kim, Kyung-Hee</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c393t-84acce1929ef316c861e16effbe5bc53dabf194ef627bb53be49aebb1984c7533</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adenocarcinoma</topic><topic>Adenocarcinoma - genetics</topic><topic>Adenocarcinoma - immunology</topic><topic>Adenocarcinoma - secondary</topic><topic>Adenocarcinoma - surgery</topic><topic>Adenocarcinoma of Lung</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Apoptosis</topic><topic>B7-H1 Antigen - analysis</topic><topic>B7-H1 Antigen - genetics</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Cancer therapies</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - immunology</topic><topic>Carcinoma, Non-Small-Cell Lung - secondary</topic><topic>Carcinoma, Non-Small-Cell Lung - surgery</topic><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Carcinoma, Squamous Cell - immunology</topic><topic>Carcinoma, Squamous Cell - secondary</topic><topic>Carcinoma, Squamous Cell - surgery</topic><topic>Cell death</topic><topic>Cloning</topic><topic>Deoxyribonucleic acid</topic><topic>Disease-Free Survival</topic><topic>DNA</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genetic Predisposition to Disease</topic><topic>Homozygote</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Kaplan-Meier Estimate</topic><topic>Ligands</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - immunology</topic><topic>Lung Neoplasms - pathology</topic><topic>Lung Neoplasms - surgery</topic><topic>Lymphatic Metastasis</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Middle Aged</topic><topic>Non–small cell lung carcinoma</topic><topic>Phenotype</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Programmed cell death 1 receptor</topic><topic>Programmed death-1 ligand-1</topic><topic>Proportional Hazards Models</topic><topic>Protein expression</topic><topic>Proteins</topic><topic>Retrospective Studies</topic><topic>Single-nucleotide polymorphism</topic><topic>Squamous cell carcinoma</topic><topic>Survival analysis</topic><topic>Time Factors</topic><topic>Tissue Array Analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yeo, Min-Kyung</creatorcontrib><creatorcontrib>Choi, Song-Yi</creatorcontrib><creatorcontrib>Seong, In-Ock</creatorcontrib><creatorcontrib>Suh, Kwang-Sun</creatorcontrib><creatorcontrib>Kim, Jin Man</creatorcontrib><creatorcontrib>Kim, Kyung-Hee</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 Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Human pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yeo, Min-Kyung</au><au>Choi, Song-Yi</au><au>Seong, In-Ock</au><au>Suh, Kwang-Sun</au><au>Kim, Jin Man</au><au>Kim, Kyung-Hee</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of PD-L1 expression and PD-L1 gene polymorphism with poor prognosis in lung adenocarcinoma and squamous cell carcinoma</atitle><jtitle>Human pathology</jtitle><addtitle>Hum Pathol</addtitle><date>2017-10</date><risdate>2017</risdate><volume>68</volume><spage>103</spage><epage>111</epage><pages>103-111</pages><issn>0046-8177</issn><eissn>1532-8392</eissn><abstract>Programmed cell death 1 receptor (PD-1)/programmed death-1 ligand-1 (PD-L1) interaction has been linked to tumor immune evasion. PD-L1 expression has been indicated in identifying non–small cell lung carcinoma (NSCLC) patients for treatment with anti–PD-1 or anti–PD-L1 therapy. The goal of this study was to evaluate the clinicopathologic values of PD-L1 expression and single-nucleotide polymorphisms (SNPs) in the PD-L1 gene in lung adenocarcinoma (ADC) and squamous cell carcinoma (SqCC). The 147 NSCLC tissues consisted of 84 samples of ADC and 63 samples of SqCC. All tissue microarray paraffin blocks were used for PD-L1 immunohistochemical assays with 22C3, SP263, and SP142 clones. Three SNPs in the PD-L1 gene, rs4143815, rs822336, and rs822337, were genotyped using SNP pyrosequencing. The PD-L1 expression was significantly higher in SqCC than in ADC. Among ADCs, PD-L1 expression was significantly higher in papillary and solid types than in lepidic and acinar types. Statistical associations of the PD-L1 expression with a shorter disease-free survival outcome and lymph node metastasis in the ADCs were found but no associations in SqCCs. Among the three SNPs, the rs4143815 genotype CC was statistically associated with positive 22C3 PD-L1 labeling in NSCLCs. The rs4143815 genotype GG instead showed a trend of shorter survival outcomes but did not reach statistical significance in the ADCs. Our results showed a significantly higher prevalence of positive PD-L1 expression in lung SqCC than in ADC. However, the PD-L1 expression and rs4143815 genotype GG might be useful for the prediction of poor prognosis in lung ADC cases.
•147 cases of non–small cell lung carcinoma were studied.•Positive PD-L1 expression was associated with poor prognosis in adenocarcinoma.•The rs4143815 genotype GG showed a trend of poor prognosis in adenocarcinoma.•The rs4143815 genotype CC was associated with PD-L1 expression.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28851662</pmid><doi>10.1016/j.humpath.2017.08.016</doi><tpages>9</tpages></addata></record> |
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subjects | Adenocarcinoma Adenocarcinoma - genetics Adenocarcinoma - immunology Adenocarcinoma - secondary Adenocarcinoma - surgery Adenocarcinoma of Lung Adult Aged Aged, 80 and over Apoptosis B7-H1 Antigen - analysis B7-H1 Antigen - genetics Biomarkers, Tumor - analysis Biomarkers, Tumor - genetics Cancer therapies Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - immunology Carcinoma, Non-Small-Cell Lung - secondary Carcinoma, Non-Small-Cell Lung - surgery Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - immunology Carcinoma, Squamous Cell - secondary Carcinoma, Squamous Cell - surgery Cell death Cloning Deoxyribonucleic acid Disease-Free Survival DNA Female Gene Expression Regulation, Neoplastic Genetic Predisposition to Disease Homozygote Hospitals Humans Immunohistochemistry Kaplan-Meier Estimate Ligands Lung cancer Lung Neoplasms - genetics Lung Neoplasms - immunology Lung Neoplasms - pathology Lung Neoplasms - surgery Lymphatic Metastasis Male Medical prognosis Middle Aged Non–small cell lung carcinoma Phenotype Polymorphism, Single Nucleotide Programmed cell death 1 receptor Programmed death-1 ligand-1 Proportional Hazards Models Protein expression Proteins Retrospective Studies Single-nucleotide polymorphism Squamous cell carcinoma Survival analysis Time Factors Tissue Array Analysis |
title | Association of PD-L1 expression and PD-L1 gene polymorphism with poor prognosis in lung adenocarcinoma and squamous cell carcinoma |
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