Sentinel Lymph Node Gene Expression Signature Predicts Recurrence-Free Survival in Cutaneous Melanoma
We sought to develop a sentinel lymph node gene expression signature score predictive of disease recurrence in patients with cutaneous melanoma. Gene expression profiling was performed on SLN biopsies using U133A 2.0 Affymetrix gene chips. The top 25 genes associated with recurrence-free survival (R...
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| Veröffentlicht in: | Cancers 2022-10, Vol.14 (20), p.4973 |
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| creator | Karapetyan, Lilit Gooding, William Li, Aofei Yang, Xi Knight, Andrew Abushukair, Hassan M Vargas De Stefano, Danielle Sander, Cindy Karunamurthy, Arivarasan Panelli, Monica Storkus, Walter J Tarhini, Ahmad A Kirkwood, John M |
| description | We sought to develop a sentinel lymph node gene expression signature score predictive of disease recurrence in patients with cutaneous melanoma. Gene expression profiling was performed on SLN biopsies using U133A 2.0 Affymetrix gene chips. The top 25 genes associated with recurrence-free survival (RFS) were selected and a penalized regression function was used to select 12 genes with a non-zero coefficient. A proportional hazards regression model was used to evaluate the association between clinical covariates, gene signature score, and RFS. Among the 45 patients evaluated, 23 (51%) had a positive SLN. Twenty-one (46.7%) patients developed disease recurrence. For the top 25 differentially expressed genes (DEG), 12 non-zero penalized coefficients were estimated (CLGN, C1QTNF3, ADORA3, ARHGAP8, DCTN1, ASPSCR1, CHRFAM7A, ZNF223, PDE6G, CXCL3, HEXIM1, HLA-DRB). This 12-gene signature score was significantly associated with RFS (p < 0.0001) and produced a bootstrap C index of 0.888. In univariate analysis, Breslow thickness, presence of primary tumor ulceration, SLN positivity were each significantly associated with RFS. After simultaneously adjusting for these prognostic factors in relation to the gene signature, the 12-gene score remained a significant independent predictor for RFS (p < 0.0001). This SLN 12-gene signature risk score is associated with melanoma recurrence regardless of SLN status and may be used as a prognostic factor for RFS. |
| doi_str_mv | 10.3390/cancers14204973 |
| format | Article |
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Gene expression profiling was performed on SLN biopsies using U133A 2.0 Affymetrix gene chips. The top 25 genes associated with recurrence-free survival (RFS) were selected and a penalized regression function was used to select 12 genes with a non-zero coefficient. A proportional hazards regression model was used to evaluate the association between clinical covariates, gene signature score, and RFS. Among the 45 patients evaluated, 23 (51%) had a positive SLN. Twenty-one (46.7%) patients developed disease recurrence. For the top 25 differentially expressed genes (DEG), 12 non-zero penalized coefficients were estimated (CLGN, C1QTNF3, ADORA3, ARHGAP8, DCTN1, ASPSCR1, CHRFAM7A, ZNF223, PDE6G, CXCL3, HEXIM1, HLA-DRB). This 12-gene signature score was significantly associated with RFS (p < 0.0001) and produced a bootstrap C index of 0.888. In univariate analysis, Breslow thickness, presence of primary tumor ulceration, SLN positivity were each significantly associated with RFS. After simultaneously adjusting for these prognostic factors in relation to the gene signature, the 12-gene score remained a significant independent predictor for RFS (p < 0.0001). This SLN 12-gene signature risk score is associated with melanoma recurrence regardless of SLN status and may be used as a prognostic factor for RFS.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers14204973</identifier><identifier>PMID: 36291758</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Biopsy ; Cancer ; Gene expression ; Genetic aspects ; Health aspects ; Lymph nodes ; Lymphatic system ; Medical prognosis ; Melanoma ; Metastases ; Metastasis ; Patients ; Prognosis ; Regulatory approval ; Relapse ; Risk assessment ; Skin cancer ; Tumors</subject><ispartof>Cancers, 2022-10, Vol.14 (20), p.4973</ispartof><rights>COPYRIGHT 2022 MDPI AG</rights><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 by the authors. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c488t-df1cef2b139f931591ca589c785e9a91f0628f3599d9e8f53e117d739d3ae85d3</citedby><cites>FETCH-LOGICAL-c488t-df1cef2b139f931591ca589c785e9a91f0628f3599d9e8f53e117d739d3ae85d3</cites><orcidid>0000-0002-4847-3718 ; 0000-0002-3570-4476 ; 0000-0002-0068-5201</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/PMC9599365/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9599365/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36291758$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Karapetyan, Lilit</creatorcontrib><creatorcontrib>Gooding, William</creatorcontrib><creatorcontrib>Li, Aofei</creatorcontrib><creatorcontrib>Yang, Xi</creatorcontrib><creatorcontrib>Knight, Andrew</creatorcontrib><creatorcontrib>Abushukair, Hassan M</creatorcontrib><creatorcontrib>Vargas De Stefano, Danielle</creatorcontrib><creatorcontrib>Sander, Cindy</creatorcontrib><creatorcontrib>Karunamurthy, Arivarasan</creatorcontrib><creatorcontrib>Panelli, Monica</creatorcontrib><creatorcontrib>Storkus, Walter J</creatorcontrib><creatorcontrib>Tarhini, Ahmad A</creatorcontrib><creatorcontrib>Kirkwood, John M</creatorcontrib><title>Sentinel Lymph Node Gene Expression Signature Predicts Recurrence-Free Survival in Cutaneous Melanoma</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>We sought to develop a sentinel lymph node gene expression signature score predictive of disease recurrence in patients with cutaneous melanoma. Gene expression profiling was performed on SLN biopsies using U133A 2.0 Affymetrix gene chips. The top 25 genes associated with recurrence-free survival (RFS) were selected and a penalized regression function was used to select 12 genes with a non-zero coefficient. A proportional hazards regression model was used to evaluate the association between clinical covariates, gene signature score, and RFS. Among the 45 patients evaluated, 23 (51%) had a positive SLN. Twenty-one (46.7%) patients developed disease recurrence. For the top 25 differentially expressed genes (DEG), 12 non-zero penalized coefficients were estimated (CLGN, C1QTNF3, ADORA3, ARHGAP8, DCTN1, ASPSCR1, CHRFAM7A, ZNF223, PDE6G, CXCL3, HEXIM1, HLA-DRB). This 12-gene signature score was significantly associated with RFS (p < 0.0001) and produced a bootstrap C index of 0.888. In univariate analysis, Breslow thickness, presence of primary tumor ulceration, SLN positivity were each significantly associated with RFS. After simultaneously adjusting for these prognostic factors in relation to the gene signature, the 12-gene score remained a significant independent predictor for RFS (p < 0.0001). This SLN 12-gene signature risk score is associated with melanoma recurrence regardless of SLN status and may be used as a prognostic factor for RFS.</description><subject>Biopsy</subject><subject>Cancer</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Lymph nodes</subject><subject>Lymphatic system</subject><subject>Medical prognosis</subject><subject>Melanoma</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Patients</subject><subject>Prognosis</subject><subject>Regulatory approval</subject><subject>Relapse</subject><subject>Risk assessment</subject><subject>Skin cancer</subject><subject>Tumors</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><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>eNptks9rHCEUx6W0NCHNubci9NLLJOOvUS-FsCRpYfuDbnsW4zw3hhnd6syS_Pd12TRNQvXgQz_v-95XHkJvSXvCmG5PnY0OciGctlxL9gId0lbSpus0f_koPkDHpdy0dTFGZCdfowPWUU2kUIcIVhCnEGHAy7txc42_ph7wJUTA57ebDKWEFPEqrKOd5gz4e4Y-uKngH-DmnKE20FxkALya8zZs7YBDxIt5shHSXPAXGGxMo32DXnk7FDi-P4_Qr4vzn4tPzfLb5efF2bJxXKmp6T1x4OkVYdprRoQmzgqlnVQCtNXEtx1Vngmtew3KCwaEyF4y3TMLSvTsCH3c627mqxF6V71lO5hNDqPNdybZYJ6-xHBt1mlrdNVknagCH-4Fcvo9Q5nMGIqDYdgbMlRSLSinnFf0_TP0Js05Vns7SnEma7f_qLUdwIToU63rdqLmTHJRSSJ2ZU_-Q9XdwxhciuBDvX-ScLpPcDmVksE_eCSt2Q2HeTYcNePd46954P-OAvsDfTS2Mw</recordid><startdate>20221011</startdate><enddate>20221011</enddate><creator>Karapetyan, Lilit</creator><creator>Gooding, William</creator><creator>Li, Aofei</creator><creator>Yang, Xi</creator><creator>Knight, Andrew</creator><creator>Abushukair, Hassan M</creator><creator>Vargas De Stefano, Danielle</creator><creator>Sander, Cindy</creator><creator>Karunamurthy, Arivarasan</creator><creator>Panelli, Monica</creator><creator>Storkus, Walter J</creator><creator>Tarhini, Ahmad A</creator><creator>Kirkwood, John M</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</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>5PM</scope><orcidid>https://orcid.org/0000-0002-4847-3718</orcidid><orcidid>https://orcid.org/0000-0002-3570-4476</orcidid><orcidid>https://orcid.org/0000-0002-0068-5201</orcidid></search><sort><creationdate>20221011</creationdate><title>Sentinel Lymph Node Gene Expression Signature Predicts Recurrence-Free Survival in Cutaneous Melanoma</title><author>Karapetyan, Lilit ; 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Gene expression profiling was performed on SLN biopsies using U133A 2.0 Affymetrix gene chips. The top 25 genes associated with recurrence-free survival (RFS) were selected and a penalized regression function was used to select 12 genes with a non-zero coefficient. A proportional hazards regression model was used to evaluate the association between clinical covariates, gene signature score, and RFS. Among the 45 patients evaluated, 23 (51%) had a positive SLN. Twenty-one (46.7%) patients developed disease recurrence. For the top 25 differentially expressed genes (DEG), 12 non-zero penalized coefficients were estimated (CLGN, C1QTNF3, ADORA3, ARHGAP8, DCTN1, ASPSCR1, CHRFAM7A, ZNF223, PDE6G, CXCL3, HEXIM1, HLA-DRB). This 12-gene signature score was significantly associated with RFS (p < 0.0001) and produced a bootstrap C index of 0.888. In univariate analysis, Breslow thickness, presence of primary tumor ulceration, SLN positivity were each significantly associated with RFS. After simultaneously adjusting for these prognostic factors in relation to the gene signature, the 12-gene score remained a significant independent predictor for RFS (p < 0.0001). This SLN 12-gene signature risk score is associated with melanoma recurrence regardless of SLN status and may be used as a prognostic factor for RFS.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>36291758</pmid><doi>10.3390/cancers14204973</doi><orcidid>https://orcid.org/0000-0002-4847-3718</orcidid><orcidid>https://orcid.org/0000-0002-3570-4476</orcidid><orcidid>https://orcid.org/0000-0002-0068-5201</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Biopsy Cancer Gene expression Genetic aspects Health aspects Lymph nodes Lymphatic system Medical prognosis Melanoma Metastases Metastasis Patients Prognosis Regulatory approval Relapse Risk assessment Skin cancer Tumors |
| title | Sentinel Lymph Node Gene Expression Signature Predicts Recurrence-Free Survival in Cutaneous Melanoma |
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