Inflammation and Apolipoproteins Are Potential Biomarkers for Stratification of Cutaneous Melanoma Patients for Immunotherapy and Targeted Therapy
Malignant cutaneous melanoma is one of the most common cancers in young adults. During the last decade, targeted and immunotherapies have significantly increased the overall survival of patients with malignant cutaneous melanoma. Nevertheless, disease progression is common, and a lack of predictive...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2021-05, Vol.81 (9), p.2545-2555 |
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| creator | Karlsson, Max J. Svedman, Fernanda Costa Tebani, Abdellah Kotol, David Hoiom, Veronica Fagerberg, Linn Edfors, Fredrik Uhlen, Mathias Brage, Suzanne Egyhazi Maddalo, Gianluca |
| description | Malignant cutaneous melanoma is one of the most common cancers in young adults. During the last decade, targeted and immunotherapies have significantly increased the overall survival of patients with malignant cutaneous melanoma. Nevertheless, disease progression is common, and a lack of predictive biomarkers of patient response to therapy hinders individualized treatment strategies. To address this issue, we performed a longitudinal study using an unbiased proteomics approach to identify and quantify proteins in plasma both before and during treatment from 109 patients treated with either targeted or immunotherapy. Linear modeling and machine learning approaches identified 43 potential prognostic and predictive biomarkers. A reverse correlation between apolipoproteins and proteins related to inflammation was observed. In the immunotherapy group, patients with low pretreatment expression of apolipoproteins and high expression of inflammation markers had shorter progression-free survival. Similarly, increased expression of LDHB during treatment elicited a significant impact on response to immunotherapy. Overall, we identified potential common and treatment-specific biomarkers in malignant cutaneous melanoma, paving the way for clinical use of these biomarkers following validation on a larger cohort.
Significance: This study identifies a potential biomarker panel that could improve the selection of therapy for patients with cutaneous melanoma. |
| doi_str_mv | 10.1158/0008-5472.CAN-20-2000 |
| format | Article |
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Significance: This study identifies a potential biomarker panel that could improve the selection of therapy for patients with cutaneous melanoma.</description><identifier>ISSN: 0008-5472</identifier><identifier>ISSN: 1538-7445</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.CAN-20-2000</identifier><identifier>PMID: 33574091</identifier><language>eng</language><publisher>PHILADELPHIA: Amer Assoc Cancer Research</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Apolipoproteins - blood ; Biomarkers, Tumor - blood ; C-Reactive Protein - analysis ; Female ; Humans ; Immune Checkpoint Inhibitors - therapeutic use ; Immunotherapy - methods ; Life Sciences & Biomedicine ; Longitudinal Studies ; Male ; Medicin och hälsovetenskap ; Melanoma - blood ; Melanoma - drug therapy ; Melanoma, Cutaneous Malignant ; Middle Aged ; Mitogen-Activated Protein Kinases - antagonists & inhibitors ; Oncology ; Prognosis ; Progression-Free Survival ; Protein Kinase Inhibitors - pharmacology ; Protein Kinase Inhibitors - therapeutic use ; Proteome - analysis ; Proteomics - methods ; Science & Technology ; Serum Amyloid A Protein - analysis ; Skin Neoplasms - blood ; Skin Neoplasms - drug therapy ; Young Adult</subject><ispartof>Cancer research (Chicago, Ill.), 2021-05, Vol.81 (9), p.2545-2555</ispartof><rights>2021 American Association for Cancer Research.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>19</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000647325600024</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c482t-e0fe892971dac0029d1388bf3014e9dd7fff9485b4c2c0ce10ff6fdd340d1daf3</citedby><cites>FETCH-LOGICAL-c482t-e0fe892971dac0029d1388bf3014e9dd7fff9485b4c2c0ce10ff6fdd340d1daf3</cites><orcidid>0000-0002-5388-3826 ; 0000-0002-0017-7987 ; 0000-0002-7000-4416 ; 0000-0002-0524-2346 ; 0000-0001-8065-3375 ; 0000-0002-8901-2678 ; 0000-0003-2297-6488 ; 0000-0003-0198-7137</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,554,782,786,887,3360,27933,27934,39267</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33574091$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-296850$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:146649635$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Karlsson, Max J.</creatorcontrib><creatorcontrib>Svedman, Fernanda Costa</creatorcontrib><creatorcontrib>Tebani, Abdellah</creatorcontrib><creatorcontrib>Kotol, David</creatorcontrib><creatorcontrib>Hoiom, Veronica</creatorcontrib><creatorcontrib>Fagerberg, Linn</creatorcontrib><creatorcontrib>Edfors, Fredrik</creatorcontrib><creatorcontrib>Uhlen, Mathias</creatorcontrib><creatorcontrib>Brage, Suzanne Egyhazi</creatorcontrib><creatorcontrib>Maddalo, Gianluca</creatorcontrib><title>Inflammation and Apolipoproteins Are Potential Biomarkers for Stratification of Cutaneous Melanoma Patients for Immunotherapy and Targeted Therapy</title><title>Cancer research (Chicago, Ill.)</title><addtitle>CANCER RES</addtitle><addtitle>Cancer Res</addtitle><description>Malignant cutaneous melanoma is one of the most common cancers in young adults. During the last decade, targeted and immunotherapies have significantly increased the overall survival of patients with malignant cutaneous melanoma. Nevertheless, disease progression is common, and a lack of predictive biomarkers of patient response to therapy hinders individualized treatment strategies. To address this issue, we performed a longitudinal study using an unbiased proteomics approach to identify and quantify proteins in plasma both before and during treatment from 109 patients treated with either targeted or immunotherapy. Linear modeling and machine learning approaches identified 43 potential prognostic and predictive biomarkers. A reverse correlation between apolipoproteins and proteins related to inflammation was observed. In the immunotherapy group, patients with low pretreatment expression of apolipoproteins and high expression of inflammation markers had shorter progression-free survival. Similarly, increased expression of LDHB during treatment elicited a significant impact on response to immunotherapy. Overall, we identified potential common and treatment-specific biomarkers in malignant cutaneous melanoma, paving the way for clinical use of these biomarkers following validation on a larger cohort.
Significance: This study identifies a potential biomarker panel that could improve the selection of therapy for patients with cutaneous melanoma.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Apolipoproteins - blood</subject><subject>Biomarkers, Tumor - blood</subject><subject>C-Reactive Protein - analysis</subject><subject>Female</subject><subject>Humans</subject><subject>Immune Checkpoint Inhibitors - therapeutic use</subject><subject>Immunotherapy - methods</subject><subject>Life Sciences & Biomedicine</subject><subject>Longitudinal Studies</subject><subject>Male</subject><subject>Medicin och hälsovetenskap</subject><subject>Melanoma - blood</subject><subject>Melanoma - drug therapy</subject><subject>Melanoma, Cutaneous Malignant</subject><subject>Middle Aged</subject><subject>Mitogen-Activated Protein Kinases - antagonists & inhibitors</subject><subject>Oncology</subject><subject>Prognosis</subject><subject>Progression-Free Survival</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Protein Kinase Inhibitors - therapeutic use</subject><subject>Proteome - analysis</subject><subject>Proteomics - methods</subject><subject>Science & Technology</subject><subject>Serum Amyloid A Protein - analysis</subject><subject>Skin Neoplasms - blood</subject><subject>Skin Neoplasms - drug therapy</subject><subject>Young Adult</subject><issn>0008-5472</issn><issn>1538-7445</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>HGBXW</sourceid><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNqNkttu1DAQhiMEokvhEUC5REIpPuZwuYTTSgUqUbi1nGTcmk3iYDuq-ho8MZNmu1yBkCJl4nzfTOz8SfKckjNKZfmaEFJmUhTsrN5-zhjBi5AHyYZKXmaFEPJhsjkyJ8mTEH7go6REPk5OOJeFIBXdJL92o-n1MOho3ZjqsUu3k-vt5CbvItgxpFsP6QXWY7S6T99YN2i_Bx9S43z6NXo0jW1X35m0nqMewc0h_QS9HpFOL_Al6quxG4Z5dPEavJ5u7wZean8FEbBYF58mj4zuAzw73E-Tb-_fXdYfs_MvH3b19jxrRcliBsRAWbGqoJ1uCWFVR3lZNoYTKqDqusIYU4lSNqJlLWmBEmNy03VckA4Vw0-TbO0bbmCaGzV5i1u7VU5bdVjaYwVK5IIXOfLVX3k8re6PdC9Skeeiyrn856y39vtWOX-l9vFasSovJUH-5cpj458zhKgGG1ro-_VsFRO4dSkLuXyWXNHWuxA8mGNzStQSFbXEQC0xUBgVxYhaooLei8OIuRmgO1r32UDg1QrcQONMaPEftnDEsEUuCs5kjhUTSJf_T9c23gWmdvMY-W-A8OBy</recordid><startdate>20210501</startdate><enddate>20210501</enddate><creator>Karlsson, Max J.</creator><creator>Svedman, Fernanda Costa</creator><creator>Tebani, Abdellah</creator><creator>Kotol, David</creator><creator>Hoiom, Veronica</creator><creator>Fagerberg, Linn</creator><creator>Edfors, Fredrik</creator><creator>Uhlen, Mathias</creator><creator>Brage, Suzanne Egyhazi</creator><creator>Maddalo, Gianluca</creator><general>Amer Assoc Cancer Research</general><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</scope><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>7X8</scope><scope>ADTPV</scope><scope>AFDQA</scope><scope>AOWAS</scope><scope>D8T</scope><scope>D8V</scope><scope>ZZAVC</scope><orcidid>https://orcid.org/0000-0002-5388-3826</orcidid><orcidid>https://orcid.org/0000-0002-0017-7987</orcidid><orcidid>https://orcid.org/0000-0002-7000-4416</orcidid><orcidid>https://orcid.org/0000-0002-0524-2346</orcidid><orcidid>https://orcid.org/0000-0001-8065-3375</orcidid><orcidid>https://orcid.org/0000-0002-8901-2678</orcidid><orcidid>https://orcid.org/0000-0003-2297-6488</orcidid><orcidid>https://orcid.org/0000-0003-0198-7137</orcidid></search><sort><creationdate>20210501</creationdate><title>Inflammation and Apolipoproteins Are Potential Biomarkers for Stratification of Cutaneous Melanoma Patients for Immunotherapy and Targeted Therapy</title><author>Karlsson, Max J. ; Svedman, Fernanda Costa ; Tebani, Abdellah ; Kotol, David ; Hoiom, Veronica ; Fagerberg, Linn ; Edfors, Fredrik ; Uhlen, Mathias ; Brage, Suzanne Egyhazi ; Maddalo, Gianluca</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c482t-e0fe892971dac0029d1388bf3014e9dd7fff9485b4c2c0ce10ff6fdd340d1daf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Apolipoproteins - blood</topic><topic>Biomarkers, Tumor - blood</topic><topic>C-Reactive Protein - analysis</topic><topic>Female</topic><topic>Humans</topic><topic>Immune Checkpoint Inhibitors - therapeutic use</topic><topic>Immunotherapy - methods</topic><topic>Life Sciences & Biomedicine</topic><topic>Longitudinal Studies</topic><topic>Male</topic><topic>Medicin och hälsovetenskap</topic><topic>Melanoma - blood</topic><topic>Melanoma - drug therapy</topic><topic>Melanoma, Cutaneous Malignant</topic><topic>Middle Aged</topic><topic>Mitogen-Activated Protein Kinases - antagonists & inhibitors</topic><topic>Oncology</topic><topic>Prognosis</topic><topic>Progression-Free Survival</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Protein Kinase Inhibitors - therapeutic use</topic><topic>Proteome - analysis</topic><topic>Proteomics - methods</topic><topic>Science & Technology</topic><topic>Serum Amyloid A Protein - analysis</topic><topic>Skin Neoplasms - blood</topic><topic>Skin Neoplasms - drug therapy</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Karlsson, Max J.</creatorcontrib><creatorcontrib>Svedman, Fernanda Costa</creatorcontrib><creatorcontrib>Tebani, Abdellah</creatorcontrib><creatorcontrib>Kotol, David</creatorcontrib><creatorcontrib>Hoiom, Veronica</creatorcontrib><creatorcontrib>Fagerberg, Linn</creatorcontrib><creatorcontrib>Edfors, Fredrik</creatorcontrib><creatorcontrib>Uhlen, Mathias</creatorcontrib><creatorcontrib>Brage, Suzanne Egyhazi</creatorcontrib><creatorcontrib>Maddalo, Gianluca</creatorcontrib><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Web of Science - Science Citation Index Expanded - 2021</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SWEPUB Kungliga Tekniska Högskolan full text</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SWEPUB Kungliga Tekniska Högskolan</collection><collection>SwePub Articles full text</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Karlsson, Max J.</au><au>Svedman, Fernanda Costa</au><au>Tebani, Abdellah</au><au>Kotol, David</au><au>Hoiom, Veronica</au><au>Fagerberg, Linn</au><au>Edfors, Fredrik</au><au>Uhlen, Mathias</au><au>Brage, Suzanne Egyhazi</au><au>Maddalo, Gianluca</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inflammation and Apolipoproteins Are Potential Biomarkers for Stratification of Cutaneous Melanoma Patients for Immunotherapy and Targeted Therapy</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><stitle>CANCER RES</stitle><addtitle>Cancer Res</addtitle><date>2021-05-01</date><risdate>2021</risdate><volume>81</volume><issue>9</issue><spage>2545</spage><epage>2555</epage><pages>2545-2555</pages><issn>0008-5472</issn><issn>1538-7445</issn><eissn>1538-7445</eissn><abstract>Malignant cutaneous melanoma is one of the most common cancers in young adults. During the last decade, targeted and immunotherapies have significantly increased the overall survival of patients with malignant cutaneous melanoma. Nevertheless, disease progression is common, and a lack of predictive biomarkers of patient response to therapy hinders individualized treatment strategies. To address this issue, we performed a longitudinal study using an unbiased proteomics approach to identify and quantify proteins in plasma both before and during treatment from 109 patients treated with either targeted or immunotherapy. Linear modeling and machine learning approaches identified 43 potential prognostic and predictive biomarkers. A reverse correlation between apolipoproteins and proteins related to inflammation was observed. In the immunotherapy group, patients with low pretreatment expression of apolipoproteins and high expression of inflammation markers had shorter progression-free survival. Similarly, increased expression of LDHB during treatment elicited a significant impact on response to immunotherapy. Overall, we identified potential common and treatment-specific biomarkers in malignant cutaneous melanoma, paving the way for clinical use of these biomarkers following validation on a larger cohort.
Significance: This study identifies a potential biomarker panel that could improve the selection of therapy for patients with cutaneous melanoma.</abstract><cop>PHILADELPHIA</cop><pub>Amer Assoc Cancer Research</pub><pmid>33574091</pmid><doi>10.1158/0008-5472.CAN-20-2000</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-5388-3826</orcidid><orcidid>https://orcid.org/0000-0002-0017-7987</orcidid><orcidid>https://orcid.org/0000-0002-7000-4416</orcidid><orcidid>https://orcid.org/0000-0002-0524-2346</orcidid><orcidid>https://orcid.org/0000-0001-8065-3375</orcidid><orcidid>https://orcid.org/0000-0002-8901-2678</orcidid><orcidid>https://orcid.org/0000-0003-2297-6488</orcidid><orcidid>https://orcid.org/0000-0003-0198-7137</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Apolipoproteins - blood Biomarkers, Tumor - blood C-Reactive Protein - analysis Female Humans Immune Checkpoint Inhibitors - therapeutic use Immunotherapy - methods Life Sciences & Biomedicine Longitudinal Studies Male Medicin och hälsovetenskap Melanoma - blood Melanoma - drug therapy Melanoma, Cutaneous Malignant Middle Aged Mitogen-Activated Protein Kinases - antagonists & inhibitors Oncology Prognosis Progression-Free Survival Protein Kinase Inhibitors - pharmacology Protein Kinase Inhibitors - therapeutic use Proteome - analysis Proteomics - methods Science & Technology Serum Amyloid A Protein - analysis Skin Neoplasms - blood Skin Neoplasms - drug therapy Young Adult |
| title | Inflammation and Apolipoproteins Are Potential Biomarkers for Stratification of Cutaneous Melanoma Patients for Immunotherapy and Targeted Therapy |
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