PD-L1 mRNA expression in EGFR-mutant lung adenocarcinoma
Molecular mechanisms of programmed death-ligand 1 (PD-L1) mRNA expression and roles of apoptosis and biomarkers are poorly understood in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma patients. Thirty-three patients with recurrent postoperative EGFR-mutant lung adenocarcinoma (ex...
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| Veröffentlicht in: | Oncology reports 2018-07, Vol.40 (1), p.331-338 |
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| creator | Isobe, Kazutoshi Kakimoto, Atsushi Mikami, Tetuo Kaburaki, Kyohei Kobayashi, Hiroshi Yoshizawa, Takahiro Nakano, Yuta Makino, Takashi Otsuka, Hajime Sano, Go Sugino, Keishi Sakamoto, Susumu Takai, Yujiro Tochigi, Naobumi Iyoda, Akira Homma, Sakae |
| description | Molecular mechanisms of programmed death-ligand 1 (PD-L1) mRNA expression and roles of apoptosis and biomarkers are poorly understood in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma patients. Thirty-three patients with recurrent postoperative EGFR-mutant lung adenocarcinoma (exon 19 deletion in 16, L858R in 15, G719C in 2 patients) treated with gefitinib were studied. PD-L1 mRNA expression of formalin-fixed paraffin-embedded paratumoral and intratumoral tissues was quantified by PCR. Correlations of PD-L1 mRNA expression with BIM, p53 upregulated modular of apoptosis (PUMA), human epidermal growth factor receptor 2 (HER2), mesenchymal-epithelial transition (MET), EGFR, and vascular endothelial growth factor A (VEGFA) were determined. Eleven of the 33 patients (33.3%) and 14/33 patients (42.4%) expressed intratumoral and paratumoral PD-L1 mRNA, respectively. Patients with intratumoral PD-L1 mRNA expression had significantly higher BIM and lower VEGFA expression compared with paratumoral PD-L1 mRNA patients (P=0.049, P=0.009). PD-L1 mRNA expression was not associated with the expression of PUMA, HER2, EGFR and MET but was positively correlated with BIM expression (r=0.41, P=0.017) and inversely correlated with VEGFA expression (r=-0.33, P=0.043). Patients with intratumoral PD-L1 mRNA expression had significantly shorter median progression-free survival (PFS) after gefitinib therapy compared with no PD-L1 expression (255 vs. 732 days, respectively; P=0.032). Thus, PD-L1 mRNA expression in EGFR-mutant lung adenocarcinoma was associated with BIM and VEGFA mRNA expression and with shorter PFS after gefitinib therapy. |
| doi_str_mv | 10.3892/or.2018.6442 |
| format | Article |
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Thirty-three patients with recurrent postoperative EGFR-mutant lung adenocarcinoma (exon 19 deletion in 16, L858R in 15, G719C in 2 patients) treated with gefitinib were studied. PD-L1 mRNA expression of formalin-fixed paraffin-embedded paratumoral and intratumoral tissues was quantified by PCR. Correlations of PD-L1 mRNA expression with BIM, p53 upregulated modular of apoptosis (PUMA), human epidermal growth factor receptor 2 (HER2), mesenchymal-epithelial transition (MET), EGFR, and vascular endothelial growth factor A (VEGFA) were determined. Eleven of the 33 patients (33.3%) and 14/33 patients (42.4%) expressed intratumoral and paratumoral PD-L1 mRNA, respectively. Patients with intratumoral PD-L1 mRNA expression had significantly higher BIM and lower VEGFA expression compared with paratumoral PD-L1 mRNA patients (P=0.049, P=0.009). PD-L1 mRNA expression was not associated with the expression of PUMA, HER2, EGFR and MET but was positively correlated with BIM expression (r=0.41, P=0.017) and inversely correlated with VEGFA expression (r=-0.33, P=0.043). Patients with intratumoral PD-L1 mRNA expression had significantly shorter median progression-free survival (PFS) after gefitinib therapy compared with no PD-L1 expression (255 vs. 732 days, respectively; P=0.032). Thus, PD-L1 mRNA expression in EGFR-mutant lung adenocarcinoma was associated with BIM and VEGFA mRNA expression and with shorter PFS after gefitinib therapy.</description><identifier>ISSN: 1021-335X</identifier><identifier>EISSN: 1791-2431</identifier><identifier>DOI: 10.3892/or.2018.6442</identifier><identifier>PMID: 29767258</identifier><language>eng</language><publisher>Greece: Spandidos Publications</publisher><subject>Adenocarcinoma - drug therapy ; Adenocarcinoma - genetics ; Adenocarcinoma - pathology ; Adenocarcinoma of Lung ; Adult ; Aged ; Apoptosis ; Apoptosis - drug effects ; B7-H1 Antigen - genetics ; Bcl-2-Like Protein 11 - genetics ; Biomarkers, Tumor - genetics ; Care and treatment ; Development and progression ; Disease control ; Disease-Free Survival ; Epidermal growth factor ; ErbB Receptors - genetics ; Female ; Gefitinib ; Gene expression ; Gene Expression Regulation, Neoplastic - drug effects ; Gene mutation ; Genetic aspects ; Health aspects ; Humans ; Kinases ; Ligands ; Lung cancer ; Lung Neoplasms - drug therapy ; Lung Neoplasms - genetics ; Lung Neoplasms - pathology ; Male ; Medical prognosis ; Messenger RNA ; Metastasis ; Middle Aged ; Mutation ; Neoplasm Proteins - genetics ; Neoplasm Recurrence, Local - drug therapy ; Neoplasm Recurrence, Local - genetics ; Neoplasm Recurrence, Local - pathology ; Quinazolines - administration & dosage ; Regression analysis ; Response rates ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - genetics</subject><ispartof>Oncology reports, 2018-07, Vol.40 (1), p.331-338</ispartof><rights>COPYRIGHT 2018 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2018</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-d7ae90680ffae2cc6b45d2f681c6fd185ef3fb9fdc0e61018a875e66f8bd85f43</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/29767258$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Isobe, Kazutoshi</creatorcontrib><creatorcontrib>Kakimoto, Atsushi</creatorcontrib><creatorcontrib>Mikami, Tetuo</creatorcontrib><creatorcontrib>Kaburaki, Kyohei</creatorcontrib><creatorcontrib>Kobayashi, Hiroshi</creatorcontrib><creatorcontrib>Yoshizawa, Takahiro</creatorcontrib><creatorcontrib>Nakano, Yuta</creatorcontrib><creatorcontrib>Makino, Takashi</creatorcontrib><creatorcontrib>Otsuka, Hajime</creatorcontrib><creatorcontrib>Sano, Go</creatorcontrib><creatorcontrib>Sugino, Keishi</creatorcontrib><creatorcontrib>Sakamoto, Susumu</creatorcontrib><creatorcontrib>Takai, Yujiro</creatorcontrib><creatorcontrib>Tochigi, Naobumi</creatorcontrib><creatorcontrib>Iyoda, Akira</creatorcontrib><creatorcontrib>Homma, Sakae</creatorcontrib><title>PD-L1 mRNA expression in EGFR-mutant lung adenocarcinoma</title><title>Oncology reports</title><addtitle>Oncol Rep</addtitle><description>Molecular mechanisms of programmed death-ligand 1 (PD-L1) mRNA expression and roles of apoptosis and biomarkers are poorly understood in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma patients. Thirty-three patients with recurrent postoperative EGFR-mutant lung adenocarcinoma (exon 19 deletion in 16, L858R in 15, G719C in 2 patients) treated with gefitinib were studied. PD-L1 mRNA expression of formalin-fixed paraffin-embedded paratumoral and intratumoral tissues was quantified by PCR. Correlations of PD-L1 mRNA expression with BIM, p53 upregulated modular of apoptosis (PUMA), human epidermal growth factor receptor 2 (HER2), mesenchymal-epithelial transition (MET), EGFR, and vascular endothelial growth factor A (VEGFA) were determined. Eleven of the 33 patients (33.3%) and 14/33 patients (42.4%) expressed intratumoral and paratumoral PD-L1 mRNA, respectively. Patients with intratumoral PD-L1 mRNA expression had significantly higher BIM and lower VEGFA expression compared with paratumoral PD-L1 mRNA patients (P=0.049, P=0.009). PD-L1 mRNA expression was not associated with the expression of PUMA, HER2, EGFR and MET but was positively correlated with BIM expression (r=0.41, P=0.017) and inversely correlated with VEGFA expression (r=-0.33, P=0.043). Patients with intratumoral PD-L1 mRNA expression had significantly shorter median progression-free survival (PFS) after gefitinib therapy compared with no PD-L1 expression (255 vs. 732 days, respectively; P=0.032). Thus, PD-L1 mRNA expression in EGFR-mutant lung adenocarcinoma was associated with BIM and VEGFA mRNA expression and with shorter PFS after gefitinib therapy.</description><subject>Adenocarcinoma - drug therapy</subject><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - pathology</subject><subject>Adenocarcinoma of Lung</subject><subject>Adult</subject><subject>Aged</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>B7-H1 Antigen - genetics</subject><subject>Bcl-2-Like Protein 11 - genetics</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Care and treatment</subject><subject>Development and progression</subject><subject>Disease control</subject><subject>Disease-Free Survival</subject><subject>Epidermal growth factor</subject><subject>ErbB Receptors - genetics</subject><subject>Female</subject><subject>Gefitinib</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Gene mutation</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Kinases</subject><subject>Ligands</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - pathology</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Messenger RNA</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Recurrence, Local - drug therapy</subject><subject>Neoplasm Recurrence, Local - genetics</subject><subject>Neoplasm Recurrence, Local - pathology</subject><subject>Quinazolines - administration & dosage</subject><subject>Regression analysis</subject><subject>Response rates</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A - genetics</subject><issn>1021-335X</issn><issn>1791-2431</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpt0ctLJDEQB-AgLr5vnqVBEA_2mEcnnRyHWR8Lwyqi4C1k0hVt6U7GpBvc_94MvtZlySEhfFWk8kNon-AJk4qehjihmMiJqCq6hrZIrUhJK0bW8xlTUjLG7zfRdkpPGNMaC7WBNqmqRU253ELy-mc5J0V_83tawMsyQkpt8EXri7OL85uyHwfjh6Ib_UNhGvDBmmhbH3qzi3440yXYe9930N352e3sspxfXfyaTeelrTgfyqY2oLCQ2DkD1FqxqHhDnZDECtcQycExt1CusRgEyXMYWXMQwslFI7mr2A46fuu7jOF5hDTovk0Wus54CGPSFDMlhaKUZ3r4D30KY_T5dVkpXjFaUfqlHkwHuvUuDNHYVVM95ZwRIXAts5r8R-XVQN_a4MG1-f5bwdFfBY9guuExhW4c8nem7_DkDdoYUorg9DK2vYl_NMF6lagOUa8S1atEMz94H2pc9NB84o8I2SusKpdE</recordid><startdate>20180701</startdate><enddate>20180701</enddate><creator>Isobe, Kazutoshi</creator><creator>Kakimoto, Atsushi</creator><creator>Mikami, Tetuo</creator><creator>Kaburaki, Kyohei</creator><creator>Kobayashi, Hiroshi</creator><creator>Yoshizawa, Takahiro</creator><creator>Nakano, Yuta</creator><creator>Makino, Takashi</creator><creator>Otsuka, Hajime</creator><creator>Sano, Go</creator><creator>Sugino, Keishi</creator><creator>Sakamoto, Susumu</creator><creator>Takai, Yujiro</creator><creator>Tochigi, Naobumi</creator><creator>Iyoda, Akira</creator><creator>Homma, Sakae</creator><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</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>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</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></search><sort><creationdate>20180701</creationdate><title>PD-L1 mRNA expression in EGFR-mutant lung adenocarcinoma</title><author>Isobe, Kazutoshi ; Kakimoto, Atsushi ; Mikami, Tetuo ; Kaburaki, Kyohei ; Kobayashi, Hiroshi ; Yoshizawa, Takahiro ; Nakano, Yuta ; Makino, Takashi ; Otsuka, Hajime ; Sano, Go ; Sugino, Keishi ; Sakamoto, Susumu ; Takai, Yujiro ; Tochigi, Naobumi ; Iyoda, Akira ; Homma, Sakae</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-d7ae90680ffae2cc6b45d2f681c6fd185ef3fb9fdc0e61018a875e66f8bd85f43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adenocarcinoma - 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Academic</collection><jtitle>Oncology reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Isobe, Kazutoshi</au><au>Kakimoto, Atsushi</au><au>Mikami, Tetuo</au><au>Kaburaki, Kyohei</au><au>Kobayashi, Hiroshi</au><au>Yoshizawa, Takahiro</au><au>Nakano, Yuta</au><au>Makino, Takashi</au><au>Otsuka, Hajime</au><au>Sano, Go</au><au>Sugino, Keishi</au><au>Sakamoto, Susumu</au><au>Takai, Yujiro</au><au>Tochigi, Naobumi</au><au>Iyoda, Akira</au><au>Homma, Sakae</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PD-L1 mRNA expression in EGFR-mutant lung adenocarcinoma</atitle><jtitle>Oncology reports</jtitle><addtitle>Oncol Rep</addtitle><date>2018-07-01</date><risdate>2018</risdate><volume>40</volume><issue>1</issue><spage>331</spage><epage>338</epage><pages>331-338</pages><issn>1021-335X</issn><eissn>1791-2431</eissn><abstract>Molecular mechanisms of programmed death-ligand 1 (PD-L1) mRNA expression and roles of apoptosis and biomarkers are poorly understood in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma patients. Thirty-three patients with recurrent postoperative EGFR-mutant lung adenocarcinoma (exon 19 deletion in 16, L858R in 15, G719C in 2 patients) treated with gefitinib were studied. PD-L1 mRNA expression of formalin-fixed paraffin-embedded paratumoral and intratumoral tissues was quantified by PCR. Correlations of PD-L1 mRNA expression with BIM, p53 upregulated modular of apoptosis (PUMA), human epidermal growth factor receptor 2 (HER2), mesenchymal-epithelial transition (MET), EGFR, and vascular endothelial growth factor A (VEGFA) were determined. Eleven of the 33 patients (33.3%) and 14/33 patients (42.4%) expressed intratumoral and paratumoral PD-L1 mRNA, respectively. Patients with intratumoral PD-L1 mRNA expression had significantly higher BIM and lower VEGFA expression compared with paratumoral PD-L1 mRNA patients (P=0.049, P=0.009). PD-L1 mRNA expression was not associated with the expression of PUMA, HER2, EGFR and MET but was positively correlated with BIM expression (r=0.41, P=0.017) and inversely correlated with VEGFA expression (r=-0.33, P=0.043). Patients with intratumoral PD-L1 mRNA expression had significantly shorter median progression-free survival (PFS) after gefitinib therapy compared with no PD-L1 expression (255 vs. 732 days, respectively; P=0.032). Thus, PD-L1 mRNA expression in EGFR-mutant lung adenocarcinoma was associated with BIM and VEGFA mRNA expression and with shorter PFS after gefitinib therapy.</abstract><cop>Greece</cop><pub>Spandidos Publications</pub><pmid>29767258</pmid><doi>10.3892/or.2018.6442</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Oncology reports, 2018-07, Vol.40 (1), p.331-338 |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adenocarcinoma - drug therapy Adenocarcinoma - genetics Adenocarcinoma - pathology Adenocarcinoma of Lung Adult Aged Apoptosis Apoptosis - drug effects B7-H1 Antigen - genetics Bcl-2-Like Protein 11 - genetics Biomarkers, Tumor - genetics Care and treatment Development and progression Disease control Disease-Free Survival Epidermal growth factor ErbB Receptors - genetics Female Gefitinib Gene expression Gene Expression Regulation, Neoplastic - drug effects Gene mutation Genetic aspects Health aspects Humans Kinases Ligands Lung cancer Lung Neoplasms - drug therapy Lung Neoplasms - genetics Lung Neoplasms - pathology Male Medical prognosis Messenger RNA Metastasis Middle Aged Mutation Neoplasm Proteins - genetics Neoplasm Recurrence, Local - drug therapy Neoplasm Recurrence, Local - genetics Neoplasm Recurrence, Local - pathology Quinazolines - administration & dosage Regression analysis Response rates Vascular endothelial growth factor Vascular Endothelial Growth Factor A - genetics |
| title | PD-L1 mRNA expression in EGFR-mutant lung adenocarcinoma |
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