FKBP51 Immunohistochemical Expression: A New Prognostic Biomarker for OSCC?
Up-to-date, several molecular markers of prognosis have been studied in Oral Squamous Cell Carcinoma (OSCC), but none entered in the clinical setting. Therapy of OSCC tumors mainly relies on surgery, radiotherapy and partially on chemotherapy; there is an urgent need for biomarkers able to better st...
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| Veröffentlicht in: | International journal of molecular sciences 2017-02, Vol.18 (2), p.443-443 |
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| creator | Russo, Daniela Merolla, Francesco Mascolo, Massimo Ilardi, Gennaro Romano, Simona Varricchio, Silvia Napolitano, Virginia Celetti, Angela Postiglione, Loredana Di Lorenzo, Pier Paolo Califano, Luigi Dell'Aversana, Giovanni Orabona Astarita, Fabio Romano, Maria Fiammetta Staibano, Stefania |
| description | Up-to-date, several molecular markers of prognosis have been studied in Oral Squamous Cell Carcinoma (OSCC), but none entered in the clinical setting. Therapy of OSCC tumors mainly relies on surgery, radiotherapy and partially on chemotherapy; there is an urgent need for biomarkers able to better stratify OSCC patients' risk to address targeted therapeutic strategies. The role of immune response in the pathogenesis and biological behavior of OSCC has been investigated by several authors, and promising results have been obtained with immune checkpoint inhibitors. We already investigated the role of the immune modulator FK506-binding protein 51 (FKBP51), a FK506-binding immunophilin, in cutaneous melanoma biology, and its expression in several human solid tumors. In the present study, we aimed to assess the value of FKBP51 expression in OSCC tumor cells as a marker of outcome. We collected clinical data from 72 patients who underwent surgery for Squamous Cell Carcinoma (SCC) of the tongue, floor, lips and palate. FKBP51 expression was assessed by immunohistochemistry on paraffin-embedded tumor tissues. In addition, we evaluated the human papillomavirus (HPV) status of primary tumors by immunohistochemistry, viral subtyping and In Situ Hybridization (ISH) assay. We found that high FKBP51-expressing tumors characterized the OSCCs with the worst prognosis: the high immunohistochemical expression of FKBP51 associated with death occurring within five years from the diagnosis with a sensitivity of 88.46% and a specificity of 91.67%. The estimated positive predictive value of the test was 88.45% and negative predictive value 91.67%. We tested FKBP51 mRNA presence, by RT-PCR assay, in a selected series of OSCC tumors, and we found that mRNA correlated well to the protein expression and to the clinical outcome. Applying the Bayes formula, we estimated an 88% probability of dying within five years from the diagnosis of OSCC patients with a high FKBP51 immunohistochemical (IHC) test result (>51% of FKBP51 positive tumor cells). On the basis of our analysis, we propose tumor tissue expression of FKBP51 protein as a reliable prognostic marker for OSCC tumors. |
| doi_str_mv | 10.3390/ijms18020443 |
| format | Article |
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Therapy of OSCC tumors mainly relies on surgery, radiotherapy and partially on chemotherapy; there is an urgent need for biomarkers able to better stratify OSCC patients' risk to address targeted therapeutic strategies. The role of immune response in the pathogenesis and biological behavior of OSCC has been investigated by several authors, and promising results have been obtained with immune checkpoint inhibitors. We already investigated the role of the immune modulator FK506-binding protein 51 (FKBP51), a FK506-binding immunophilin, in cutaneous melanoma biology, and its expression in several human solid tumors. In the present study, we aimed to assess the value of FKBP51 expression in OSCC tumor cells as a marker of outcome. We collected clinical data from 72 patients who underwent surgery for Squamous Cell Carcinoma (SCC) of the tongue, floor, lips and palate. FKBP51 expression was assessed by immunohistochemistry on paraffin-embedded tumor tissues. In addition, we evaluated the human papillomavirus (HPV) status of primary tumors by immunohistochemistry, viral subtyping and In Situ Hybridization (ISH) assay. We found that high FKBP51-expressing tumors characterized the OSCCs with the worst prognosis: the high immunohistochemical expression of FKBP51 associated with death occurring within five years from the diagnosis with a sensitivity of 88.46% and a specificity of 91.67%. The estimated positive predictive value of the test was 88.45% and negative predictive value 91.67%. We tested FKBP51 mRNA presence, by RT-PCR assay, in a selected series of OSCC tumors, and we found that mRNA correlated well to the protein expression and to the clinical outcome. Applying the Bayes formula, we estimated an 88% probability of dying within five years from the diagnosis of OSCC patients with a high FKBP51 immunohistochemical (IHC) test result (>51% of FKBP51 positive tumor cells). On the basis of our analysis, we propose tumor tissue expression of FKBP51 protein as a reliable prognostic marker for OSCC tumors.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms18020443</identifier><identifier>PMID: 28218707</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Bayesian analysis ; Biomarkers, Tumor ; Carcinoma, Squamous Cell - diagnosis ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - mortality ; Carcinoma, Squamous Cell - therapy ; Chemotherapy ; Cyclin-Dependent Kinase Inhibitor p16 - genetics ; Cyclin-Dependent Kinase Inhibitor p16 - metabolism ; Diagnosis ; Female ; Gene Expression ; Human papillomavirus ; Human papillomavirus 16 - physiology ; Humans ; Immune checkpoint inhibitors ; Immune response ; Immune system ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Male ; Melanoma ; Middle Aged ; Mouth Neoplasms - diagnosis ; Mouth Neoplasms - metabolism ; Mouth Neoplasms - mortality ; Mouth Neoplasms - therapy ; mRNA ; Neoplasm Grading ; Neoplasm Staging ; Oral squamous cell carcinoma ; Palate ; Papillomaviridae ; Patients ; Polymerase chain reaction ; Prognosis ; Proteins ; Radiation therapy ; Solid tumors ; Squamous cell carcinoma ; Surgery ; Tacrolimus ; Tacrolimus Binding Proteins - genetics ; Tacrolimus Binding Proteins - metabolism ; Tacrolimus-binding protein ; Tongue ; Tumor cells ; Tumors</subject><ispartof>International journal of molecular sciences, 2017-02, Vol.18 (2), p.443-443</ispartof><rights>Copyright MDPI AG 2017</rights><rights>2017 by the authors. 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c445t-aa35d3d8c171aaa70cf069f0c74bad864c53c939eef3182be928a88aaab39b763</citedby><cites>FETCH-LOGICAL-c445t-aa35d3d8c171aaa70cf069f0c74bad864c53c939eef3182be928a88aaab39b763</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343977/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343977/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,883,27911,27912,53778,53780</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28218707$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Russo, Daniela</creatorcontrib><creatorcontrib>Merolla, Francesco</creatorcontrib><creatorcontrib>Mascolo, Massimo</creatorcontrib><creatorcontrib>Ilardi, Gennaro</creatorcontrib><creatorcontrib>Romano, Simona</creatorcontrib><creatorcontrib>Varricchio, Silvia</creatorcontrib><creatorcontrib>Napolitano, Virginia</creatorcontrib><creatorcontrib>Celetti, Angela</creatorcontrib><creatorcontrib>Postiglione, Loredana</creatorcontrib><creatorcontrib>Di Lorenzo, Pier Paolo</creatorcontrib><creatorcontrib>Califano, Luigi</creatorcontrib><creatorcontrib>Dell'Aversana, Giovanni Orabona</creatorcontrib><creatorcontrib>Astarita, Fabio</creatorcontrib><creatorcontrib>Romano, Maria Fiammetta</creatorcontrib><creatorcontrib>Staibano, Stefania</creatorcontrib><title>FKBP51 Immunohistochemical Expression: A New Prognostic Biomarker for OSCC?</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Up-to-date, several molecular markers of prognosis have been studied in Oral Squamous Cell Carcinoma (OSCC), but none entered in the clinical setting. Therapy of OSCC tumors mainly relies on surgery, radiotherapy and partially on chemotherapy; there is an urgent need for biomarkers able to better stratify OSCC patients' risk to address targeted therapeutic strategies. The role of immune response in the pathogenesis and biological behavior of OSCC has been investigated by several authors, and promising results have been obtained with immune checkpoint inhibitors. We already investigated the role of the immune modulator FK506-binding protein 51 (FKBP51), a FK506-binding immunophilin, in cutaneous melanoma biology, and its expression in several human solid tumors. In the present study, we aimed to assess the value of FKBP51 expression in OSCC tumor cells as a marker of outcome. We collected clinical data from 72 patients who underwent surgery for Squamous Cell Carcinoma (SCC) of the tongue, floor, lips and palate. FKBP51 expression was assessed by immunohistochemistry on paraffin-embedded tumor tissues. In addition, we evaluated the human papillomavirus (HPV) status of primary tumors by immunohistochemistry, viral subtyping and In Situ Hybridization (ISH) assay. We found that high FKBP51-expressing tumors characterized the OSCCs with the worst prognosis: the high immunohistochemical expression of FKBP51 associated with death occurring within five years from the diagnosis with a sensitivity of 88.46% and a specificity of 91.67%. The estimated positive predictive value of the test was 88.45% and negative predictive value 91.67%. We tested FKBP51 mRNA presence, by RT-PCR assay, in a selected series of OSCC tumors, and we found that mRNA correlated well to the protein expression and to the clinical outcome. Applying the Bayes formula, we estimated an 88% probability of dying within five years from the diagnosis of OSCC patients with a high FKBP51 immunohistochemical (IHC) test result (>51% of FKBP51 positive tumor cells). On the basis of our analysis, we propose tumor tissue expression of FKBP51 protein as a reliable prognostic marker for OSCC tumors.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Bayesian analysis</subject><subject>Biomarkers, Tumor</subject><subject>Carcinoma, Squamous Cell - diagnosis</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - mortality</subject><subject>Carcinoma, Squamous Cell - therapy</subject><subject>Chemotherapy</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - genetics</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - metabolism</subject><subject>Diagnosis</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Human papillomavirus</subject><subject>Human papillomavirus 16 - physiology</subject><subject>Humans</subject><subject>Immune checkpoint inhibitors</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunohistochemistry</subject><subject>Kaplan-Meier Estimate</subject><subject>Lymphatic Metastasis</subject><subject>Male</subject><subject>Melanoma</subject><subject>Middle Aged</subject><subject>Mouth Neoplasms - diagnosis</subject><subject>Mouth Neoplasms - metabolism</subject><subject>Mouth Neoplasms - mortality</subject><subject>Mouth Neoplasms - therapy</subject><subject>mRNA</subject><subject>Neoplasm Grading</subject><subject>Neoplasm Staging</subject><subject>Oral squamous cell carcinoma</subject><subject>Palate</subject><subject>Papillomaviridae</subject><subject>Patients</subject><subject>Polymerase chain reaction</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>Radiation therapy</subject><subject>Solid tumors</subject><subject>Squamous cell carcinoma</subject><subject>Surgery</subject><subject>Tacrolimus</subject><subject>Tacrolimus Binding Proteins - genetics</subject><subject>Tacrolimus Binding Proteins - metabolism</subject><subject>Tacrolimus-binding protein</subject><subject>Tongue</subject><subject>Tumor cells</subject><subject>Tumors</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNkUlPwzAQhS0EYincOKNIXDhQsD1ObHMAlYpNIEACzpbjOtQliYudsPx7wqrCidOMNJ-e3ryH0DrBOwAS77pJFYnAFDMGc2iZMEr7GGd8fmZfQisxTjCmQFO5iJaooERwzJfR-fH54XVKkrOqams_drHxZmwrZ3SZHL1Mg43R-XovGSSX9jm5Dv6-9rFxJjl0vtLhwYak8CG5uhkOD1bRQqHLaNe-Zg_dHR_dDk_7F1cnZ8PBRd8wljZ9rSEdwUgYwonWmmNT4EwW2HCW65HImEnBSJDWFkAEza2kQgvRoTnInGfQQ_ufutM2r-zI2LoJulTT4DpHr8prp35fajdW9_5JpcBAct4JbH0JBP_Y2tioykVjy1LX1rdRESG7eERG8D9QjjMG8IFu_kEnvg11l8Q7JRgw0VXUQ9uflAk-xmCLH98Eq_dC1WyhHb4x--sP_N0gvAEa05sl</recordid><startdate>20170218</startdate><enddate>20170218</enddate><creator>Russo, Daniela</creator><creator>Merolla, Francesco</creator><creator>Mascolo, Massimo</creator><creator>Ilardi, Gennaro</creator><creator>Romano, Simona</creator><creator>Varricchio, Silvia</creator><creator>Napolitano, Virginia</creator><creator>Celetti, Angela</creator><creator>Postiglione, Loredana</creator><creator>Di Lorenzo, Pier Paolo</creator><creator>Califano, Luigi</creator><creator>Dell'Aversana, Giovanni Orabona</creator><creator>Astarita, Fabio</creator><creator>Romano, Maria Fiammetta</creator><creator>Staibano, Stefania</creator><general>MDPI AG</general><general>MDPI</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>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>7TK</scope><scope>5PM</scope></search><sort><creationdate>20170218</creationdate><title>FKBP51 Immunohistochemical Expression: A New Prognostic Biomarker for OSCC?</title><author>Russo, Daniela ; Merolla, Francesco ; Mascolo, Massimo ; Ilardi, Gennaro ; Romano, Simona ; Varricchio, Silvia ; Napolitano, Virginia ; Celetti, Angela ; Postiglione, Loredana ; Di Lorenzo, Pier Paolo ; Califano, Luigi ; Dell'Aversana, Giovanni Orabona ; Astarita, Fabio ; Romano, Maria Fiammetta ; Staibano, Stefania</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c445t-aa35d3d8c171aaa70cf069f0c74bad864c53c939eef3182be928a88aaab39b763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Bayesian analysis</topic><topic>Biomarkers, Tumor</topic><topic>Carcinoma, Squamous Cell - 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Academic</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Russo, Daniela</au><au>Merolla, Francesco</au><au>Mascolo, Massimo</au><au>Ilardi, Gennaro</au><au>Romano, Simona</au><au>Varricchio, Silvia</au><au>Napolitano, Virginia</au><au>Celetti, Angela</au><au>Postiglione, Loredana</au><au>Di Lorenzo, Pier Paolo</au><au>Califano, Luigi</au><au>Dell'Aversana, Giovanni Orabona</au><au>Astarita, Fabio</au><au>Romano, Maria Fiammetta</au><au>Staibano, Stefania</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>FKBP51 Immunohistochemical Expression: A New Prognostic Biomarker for OSCC?</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2017-02-18</date><risdate>2017</risdate><volume>18</volume><issue>2</issue><spage>443</spage><epage>443</epage><pages>443-443</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Up-to-date, several molecular markers of prognosis have been studied in Oral Squamous Cell Carcinoma (OSCC), but none entered in the clinical setting. Therapy of OSCC tumors mainly relies on surgery, radiotherapy and partially on chemotherapy; there is an urgent need for biomarkers able to better stratify OSCC patients' risk to address targeted therapeutic strategies. The role of immune response in the pathogenesis and biological behavior of OSCC has been investigated by several authors, and promising results have been obtained with immune checkpoint inhibitors. We already investigated the role of the immune modulator FK506-binding protein 51 (FKBP51), a FK506-binding immunophilin, in cutaneous melanoma biology, and its expression in several human solid tumors. In the present study, we aimed to assess the value of FKBP51 expression in OSCC tumor cells as a marker of outcome. We collected clinical data from 72 patients who underwent surgery for Squamous Cell Carcinoma (SCC) of the tongue, floor, lips and palate. FKBP51 expression was assessed by immunohistochemistry on paraffin-embedded tumor tissues. In addition, we evaluated the human papillomavirus (HPV) status of primary tumors by immunohistochemistry, viral subtyping and In Situ Hybridization (ISH) assay. We found that high FKBP51-expressing tumors characterized the OSCCs with the worst prognosis: the high immunohistochemical expression of FKBP51 associated with death occurring within five years from the diagnosis with a sensitivity of 88.46% and a specificity of 91.67%. The estimated positive predictive value of the test was 88.45% and negative predictive value 91.67%. We tested FKBP51 mRNA presence, by RT-PCR assay, in a selected series of OSCC tumors, and we found that mRNA correlated well to the protein expression and to the clinical outcome. Applying the Bayes formula, we estimated an 88% probability of dying within five years from the diagnosis of OSCC patients with a high FKBP51 immunohistochemical (IHC) test result (>51% of FKBP51 positive tumor cells). On the basis of our analysis, we propose tumor tissue expression of FKBP51 protein as a reliable prognostic marker for OSCC tumors.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>28218707</pmid><doi>10.3390/ijms18020443</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1422-0067 |
| ispartof | International journal of molecular sciences, 2017-02, Vol.18 (2), p.443-443 |
| issn | 1422-0067 1661-6596 1422-0067 |
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| source | MEDLINE; MDPI - Multidisciplinary Digital Publishing Institute; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Adult Aged Aged, 80 and over Bayesian analysis Biomarkers, Tumor Carcinoma, Squamous Cell - diagnosis Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - mortality Carcinoma, Squamous Cell - therapy Chemotherapy Cyclin-Dependent Kinase Inhibitor p16 - genetics Cyclin-Dependent Kinase Inhibitor p16 - metabolism Diagnosis Female Gene Expression Human papillomavirus Human papillomavirus 16 - physiology Humans Immune checkpoint inhibitors Immune response Immune system Immunohistochemistry Kaplan-Meier Estimate Lymphatic Metastasis Male Melanoma Middle Aged Mouth Neoplasms - diagnosis Mouth Neoplasms - metabolism Mouth Neoplasms - mortality Mouth Neoplasms - therapy mRNA Neoplasm Grading Neoplasm Staging Oral squamous cell carcinoma Palate Papillomaviridae Patients Polymerase chain reaction Prognosis Proteins Radiation therapy Solid tumors Squamous cell carcinoma Surgery Tacrolimus Tacrolimus Binding Proteins - genetics Tacrolimus Binding Proteins - metabolism Tacrolimus-binding protein Tongue Tumor cells Tumors |
| title | FKBP51 Immunohistochemical Expression: A New Prognostic Biomarker for OSCC? |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-16T00%3A51%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=FKBP51%20Immunohistochemical%20Expression:%20A%20New%20Prognostic%20Biomarker%20for%20OSCC?&rft.jtitle=International%20journal%20of%20molecular%20sciences&rft.au=Russo,%20Daniela&rft.date=2017-02-18&rft.volume=18&rft.issue=2&rft.spage=443&rft.epage=443&rft.pages=443-443&rft.issn=1422-0067&rft.eissn=1422-0067&rft_id=info:doi/10.3390/ijms18020443&rft_dat=%3Cproquest_pubme%3E4320952275%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1878434844&rft_id=info:pmid/28218707&rfr_iscdi=true |