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Increased Soluble PD-L1 Levels in the Plasma of Patients with Epithelial Ovarian Cancer Correlate with Plasma Levels of miR34a and miR200
Recently, programmed cell death protein 1 (PD1) blocking and anti-programmed death-ligand 1 (PD-L1) agents were approved for the treatment of various human malignancies. Our study examined the expression of PD-L1 in neoplastic tissue (17 patients) and the plasma soluble (s)PD-L1 of 32 patients with...
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Published in: | Anticancer research 2018-10, Vol.38 (10), p.5739-5745 |
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container_start_page | 5739 |
container_title | Anticancer research |
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creator | Koukourakis, Michael I Kontomanolis, Emmanuel Sotiropoulou, Maria Mitrakas, Achilleas Dafa, Evangelia Pouliliou, Stamatia Sivridis, Efthimios Giatromanolaki, Alexandra |
description | Recently, programmed cell death protein 1 (PD1) blocking and anti-programmed death-ligand 1 (PD-L1) agents were approved for the treatment of various human malignancies.
Our study examined the expression of PD-L1 in neoplastic tissue (17 patients) and the plasma soluble (s)PD-L1 of 32 patients with ovarian carcinoma, in parallel with the levels of specific microRNAs (miRs), using immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively.
PD-L1 levels were significantly higher in the plasma of patients with ovarian cancer compared to healthy women (p=0.01). High miR200 levels were related to high sPD-L1 levels (p=0.03), whilst high miR34a levels were associated with low sPD-L1 levels (p=0.02). Immunohistochemical expression of PD-L1 by cancer cells was not related to plasma miR levels, nor to the level of sPD-L1.
As well as cancer cell expression of PD-L1, a high sPD-L1 level characterizes a subset of patients with ovarian cancer. The value of this latter feature as a biomarker for the administration of anti-PD-L1/PD1 therapy needs further evaluation. Micro-RNAs, such as miR34a and miR200, may have a role in the efficacy of immunotherapy. |
doi_str_mv | 10.21873/anticanres.12912 |
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Our study examined the expression of PD-L1 in neoplastic tissue (17 patients) and the plasma soluble (s)PD-L1 of 32 patients with ovarian carcinoma, in parallel with the levels of specific microRNAs (miRs), using immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively.
PD-L1 levels were significantly higher in the plasma of patients with ovarian cancer compared to healthy women (p=0.01). High miR200 levels were related to high sPD-L1 levels (p=0.03), whilst high miR34a levels were associated with low sPD-L1 levels (p=0.02). Immunohistochemical expression of PD-L1 by cancer cells was not related to plasma miR levels, nor to the level of sPD-L1.
As well as cancer cell expression of PD-L1, a high sPD-L1 level characterizes a subset of patients with ovarian cancer. The value of this latter feature as a biomarker for the administration of anti-PD-L1/PD1 therapy needs further evaluation. Micro-RNAs, such as miR34a and miR200, may have a role in the efficacy of immunotherapy.</description><identifier>ISSN: 0250-7005</identifier><identifier>EISSN: 1791-7530</identifier><identifier>DOI: 10.21873/anticanres.12912</identifier><identifier>PMID: 30275195</identifier><language>eng</language><publisher>Greece: International Institute of Anticancer Research</publisher><subject>Apoptosis ; B7-H1 Antigen - blood ; Biomarkers ; Biomarkers, Tumor - blood ; Cancer ; Case-Control Studies ; Cell death ; Cystadenocarcinoma, Serous - blood ; Cystadenocarcinoma, Serous - pathology ; Cystadenocarcinoma, Serous - surgery ; Enzyme-linked immunosorbent assay ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Immunotherapy ; MicroRNAs - blood ; miRNA ; Ovarian cancer ; Ovarian carcinoma ; Ovarian Neoplasms - blood ; Ovarian Neoplasms - pathology ; Ovarian Neoplasms - surgery ; Patients ; PD-1 protein ; PD-L1 protein ; Pilot Projects ; Plasma levels ; Polymerase chain reaction ; Prognosis ; Proteins ; Reverse transcription</subject><ispartof>Anticancer research, 2018-10, Vol.38 (10), p.5739-5745</ispartof><rights>Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.</rights><rights>Copyright International Institute of Anticancer Research Oct 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-311d48743325297cd07166a0321558603e525633e12389fb0aeadf57116f9aa83</citedby></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/30275195$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Koukourakis, Michael I</creatorcontrib><creatorcontrib>Kontomanolis, Emmanuel</creatorcontrib><creatorcontrib>Sotiropoulou, Maria</creatorcontrib><creatorcontrib>Mitrakas, Achilleas</creatorcontrib><creatorcontrib>Dafa, Evangelia</creatorcontrib><creatorcontrib>Pouliliou, Stamatia</creatorcontrib><creatorcontrib>Sivridis, Efthimios</creatorcontrib><creatorcontrib>Giatromanolaki, Alexandra</creatorcontrib><title>Increased Soluble PD-L1 Levels in the Plasma of Patients with Epithelial Ovarian Cancer Correlate with Plasma Levels of miR34a and miR200</title><title>Anticancer research</title><addtitle>Anticancer Res</addtitle><description>Recently, programmed cell death protein 1 (PD1) blocking and anti-programmed death-ligand 1 (PD-L1) agents were approved for the treatment of various human malignancies.
Our study examined the expression of PD-L1 in neoplastic tissue (17 patients) and the plasma soluble (s)PD-L1 of 32 patients with ovarian carcinoma, in parallel with the levels of specific microRNAs (miRs), using immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively.
PD-L1 levels were significantly higher in the plasma of patients with ovarian cancer compared to healthy women (p=0.01). High miR200 levels were related to high sPD-L1 levels (p=0.03), whilst high miR34a levels were associated with low sPD-L1 levels (p=0.02). Immunohistochemical expression of PD-L1 by cancer cells was not related to plasma miR levels, nor to the level of sPD-L1.
As well as cancer cell expression of PD-L1, a high sPD-L1 level characterizes a subset of patients with ovarian cancer. The value of this latter feature as a biomarker for the administration of anti-PD-L1/PD1 therapy needs further evaluation. Micro-RNAs, such as miR34a and miR200, may have a role in the efficacy of immunotherapy.</description><subject>Apoptosis</subject><subject>B7-H1 Antigen - blood</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - blood</subject><subject>Cancer</subject><subject>Case-Control Studies</subject><subject>Cell death</subject><subject>Cystadenocarcinoma, Serous - blood</subject><subject>Cystadenocarcinoma, Serous - pathology</subject><subject>Cystadenocarcinoma, Serous - surgery</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Immunotherapy</subject><subject>MicroRNAs - blood</subject><subject>miRNA</subject><subject>Ovarian cancer</subject><subject>Ovarian carcinoma</subject><subject>Ovarian Neoplasms - blood</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Ovarian Neoplasms - surgery</subject><subject>Patients</subject><subject>PD-1 protein</subject><subject>PD-L1 protein</subject><subject>Pilot Projects</subject><subject>Plasma levels</subject><subject>Polymerase chain reaction</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>Reverse transcription</subject><issn>0250-7005</issn><issn>1791-7530</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNpdkc9q3DAQh0VoabZpHyCXIOilF6cazcqyjmWTtoGFhP45m1l7TBRkeSvZG_oIfet6s9sUepkZhm8-Bn5CnIO61FBZ_EBx9A3FxPkStAN9IhZgHRTWoHohFkobVVilzKl4nfODUmXpKnwlTlFpa8CZhfh9E5vElLmV34YwbQLLu6tiDXLNOw5Z-ijH-3kXKPckh07e0eg5jlk--vFeXm_nysFTkLc7Sp6iXFFsOMnVkBIHGvkAHgVH6-zp_VdckqTY7ket1BvxsqOQ-e2xn4kfn66_r74U69vPN6uP66JBq8cCAdplZZeI2mhnm1ZZKEtSqMGYqlTIRpsSkUFj5bqNIqa2Mxag7BxRhWfi_cG7TcPPifNY9z43HAJFHqZcawBjl9apPfruP_RhmFKcv5spnJXoYE_BgWrSkHPirt4m31P6VYOqn3Kq_-VUP-U031wczdOm5_b54m8w-AfBTI32</recordid><startdate>201810</startdate><enddate>201810</enddate><creator>Koukourakis, Michael I</creator><creator>Kontomanolis, Emmanuel</creator><creator>Sotiropoulou, Maria</creator><creator>Mitrakas, Achilleas</creator><creator>Dafa, Evangelia</creator><creator>Pouliliou, Stamatia</creator><creator>Sivridis, Efthimios</creator><creator>Giatromanolaki, Alexandra</creator><general>International Institute of Anticancer Research</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>7QO</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201810</creationdate><title>Increased Soluble PD-L1 Levels in the Plasma of Patients with Epithelial Ovarian Cancer Correlate with Plasma Levels of miR34a and miR200</title><author>Koukourakis, Michael I ; Kontomanolis, Emmanuel ; Sotiropoulou, Maria ; Mitrakas, Achilleas ; Dafa, Evangelia ; Pouliliou, Stamatia ; Sivridis, Efthimios ; Giatromanolaki, Alexandra</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-311d48743325297cd07166a0321558603e525633e12389fb0aeadf57116f9aa83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Apoptosis</topic><topic>B7-H1 Antigen - blood</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - blood</topic><topic>Cancer</topic><topic>Case-Control Studies</topic><topic>Cell death</topic><topic>Cystadenocarcinoma, Serous - blood</topic><topic>Cystadenocarcinoma, Serous - pathology</topic><topic>Cystadenocarcinoma, Serous - surgery</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Immunotherapy</topic><topic>MicroRNAs - blood</topic><topic>miRNA</topic><topic>Ovarian cancer</topic><topic>Ovarian carcinoma</topic><topic>Ovarian Neoplasms - blood</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Ovarian Neoplasms - surgery</topic><topic>Patients</topic><topic>PD-1 protein</topic><topic>PD-L1 protein</topic><topic>Pilot Projects</topic><topic>Plasma levels</topic><topic>Polymerase chain reaction</topic><topic>Prognosis</topic><topic>Proteins</topic><topic>Reverse transcription</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Koukourakis, Michael I</creatorcontrib><creatorcontrib>Kontomanolis, Emmanuel</creatorcontrib><creatorcontrib>Sotiropoulou, Maria</creatorcontrib><creatorcontrib>Mitrakas, Achilleas</creatorcontrib><creatorcontrib>Dafa, Evangelia</creatorcontrib><creatorcontrib>Pouliliou, Stamatia</creatorcontrib><creatorcontrib>Sivridis, Efthimios</creatorcontrib><creatorcontrib>Giatromanolaki, Alexandra</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</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><jtitle>Anticancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Koukourakis, Michael I</au><au>Kontomanolis, Emmanuel</au><au>Sotiropoulou, Maria</au><au>Mitrakas, Achilleas</au><au>Dafa, Evangelia</au><au>Pouliliou, Stamatia</au><au>Sivridis, Efthimios</au><au>Giatromanolaki, Alexandra</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased Soluble PD-L1 Levels in the Plasma of Patients with Epithelial Ovarian Cancer Correlate with Plasma Levels of miR34a and miR200</atitle><jtitle>Anticancer research</jtitle><addtitle>Anticancer Res</addtitle><date>2018-10</date><risdate>2018</risdate><volume>38</volume><issue>10</issue><spage>5739</spage><epage>5745</epage><pages>5739-5745</pages><issn>0250-7005</issn><eissn>1791-7530</eissn><abstract>Recently, programmed cell death protein 1 (PD1) blocking and anti-programmed death-ligand 1 (PD-L1) agents were approved for the treatment of various human malignancies.
Our study examined the expression of PD-L1 in neoplastic tissue (17 patients) and the plasma soluble (s)PD-L1 of 32 patients with ovarian carcinoma, in parallel with the levels of specific microRNAs (miRs), using immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively.
PD-L1 levels were significantly higher in the plasma of patients with ovarian cancer compared to healthy women (p=0.01). High miR200 levels were related to high sPD-L1 levels (p=0.03), whilst high miR34a levels were associated with low sPD-L1 levels (p=0.02). Immunohistochemical expression of PD-L1 by cancer cells was not related to plasma miR levels, nor to the level of sPD-L1.
As well as cancer cell expression of PD-L1, a high sPD-L1 level characterizes a subset of patients with ovarian cancer. The value of this latter feature as a biomarker for the administration of anti-PD-L1/PD1 therapy needs further evaluation. Micro-RNAs, such as miR34a and miR200, may have a role in the efficacy of immunotherapy.</abstract><cop>Greece</cop><pub>International Institute of Anticancer Research</pub><pmid>30275195</pmid><doi>10.21873/anticanres.12912</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Apoptosis B7-H1 Antigen - blood Biomarkers Biomarkers, Tumor - blood Cancer Case-Control Studies Cell death Cystadenocarcinoma, Serous - blood Cystadenocarcinoma, Serous - pathology Cystadenocarcinoma, Serous - surgery Enzyme-linked immunosorbent assay Female Follow-Up Studies Humans Immunohistochemistry Immunotherapy MicroRNAs - blood miRNA Ovarian cancer Ovarian carcinoma Ovarian Neoplasms - blood Ovarian Neoplasms - pathology Ovarian Neoplasms - surgery Patients PD-1 protein PD-L1 protein Pilot Projects Plasma levels Polymerase chain reaction Prognosis Proteins Reverse transcription |
title | Increased Soluble PD-L1 Levels in the Plasma of Patients with Epithelial Ovarian Cancer Correlate with Plasma Levels of miR34a and miR200 |
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