Tumor‐associated autoantibodies as early detection markers for ovarian cancer? A prospective evaluation
Immuno‐proteomic screening has identified several tumor‐associated autoantibodies (AAb) that may have diagnostic capacity for invasive epithelial ovarian cancer, with AAbs to P53 proteins and cancer‐testis antigens (CTAGs) as prominent examples. However, the early detection potential of these AAbs h...
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| Veröffentlicht in: | International journal of cancer 2018-08, Vol.143 (3), p.515-526 |
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| creator | Kaaks, Rudolf Fortner, Renée Turzanski Hüsing, Anika Barrdahl, Myrto Hopper, Marika Johnson, Theron Tjønneland, Anne Hansen, Louise Overvad, Kim Fournier, Agnès Boutron‐Ruault, Marie‐Christine Kvaskoff, Marina Dossus, Laure Johansson, Mattias Boeing, Heiner Trichopoulou, Antonia Benetou, Vassiliki La Vecchia, Carlo Sieri, Sabina Mattiello, Amalia Palli, Domenico Tumino, Rosario Matullo, Giuseppe Onland‐Moret, N. Charlotte Gram, Inger T. Weiderpass, Elisabete Sánchez, Maria‐Jose Navarro Sanchez, Carmen Duell, Eric J. Ardanaz, Eva Larranaga, Nerea Lundin, Eva Idahl, Annika Jirström, Karin Nodin, Björn Travis, Ruth C. Riboli, Elio Merritt, Melissa Aune, Dagfinn Terry, Kathryn Cramer, Daniel W. Anderson, Karen S. |
| description | Immuno‐proteomic screening has identified several tumor‐associated autoantibodies (AAb) that may have diagnostic capacity for invasive epithelial ovarian cancer, with AAbs to P53 proteins and cancer‐testis antigens (CTAGs) as prominent examples. However, the early detection potential of these AAbs has been insufficiently explored in prospective studies. We performed ELISA measurements of AAbs to CTAG1A, CTAG2, P53 and NUDT11 proteins, for 194 patients with ovarian cancer and 705 matched controls from the European EPIC cohort, using serum samples collected up to 36 months prior to diagnosis under usual care. CA125 was measured using electrochemo‐luminiscence. Diagnostic discrimination statistics were calculated by strata of lead‐time between blood collection and diagnosis. With lead times ≤6 months, ovarian cancer detection sensitivity at 0.98 specificity (SE98) varied from 0.19 [95% CI 0.08–0.40] for CTAG1A, CTAG2 and NUDT1 to 0.23 [0.10–0.44] for P53 (0.33 [0.11–0.68] for high‐grade serous tumors). However, at longer lead‐times, the ability of these AAb markers to distinguish future ovarian cancer cases from controls declined rapidly; at lead times >1 year, SE98 estimates were close to zero (all invasive cases, range: 0.01–0.11). Compared to CA125 alone, combined logistic regression scores of AAbs and CA125 did not improve detection sensitivity at equal level of specificity. The added value of these selected AAbs as markers for ovarian cancer beyond CA125 for early detection is therefore limited.
What's new?
Could autoantibodies against tumor antigens provide an early warning system for ovarian cancer? These authors tested how well certain antibodies detected ovarian cancer. They selected four candidate antibodies, to p53, CTAG1A, CTAG2 and NUDT11 proteins, which appear in elevated levels in cancer patients. None of them performed well as a herald of burgeoning cancer. They did not perform any better than the best currently available biomarker, CA125, and as lead times increased past 6 months prediagnosis, the effectiveness diminished. Surprisingly, elevated antibodies appeared in quite a few of the control samples, suggesting they might not be as cancer‐specific as expected. |
| doi_str_mv | 10.1002/ijc.31335 |
| format | Article |
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What's new?
Could autoantibodies against tumor antigens provide an early warning system for ovarian cancer? These authors tested how well certain antibodies detected ovarian cancer. They selected four candidate antibodies, to p53, CTAG1A, CTAG2 and NUDT11 proteins, which appear in elevated levels in cancer patients. None of them performed well as a herald of burgeoning cancer. They did not perform any better than the best currently available biomarker, CA125, and as lead times increased past 6 months prediagnosis, the effectiveness diminished. Surprisingly, elevated antibodies appeared in quite a few of the control samples, suggesting they might not be as cancer‐specific as expected.</description><identifier>ISSN: 0020-7136</identifier><identifier>ISSN: 1097-0215</identifier><identifier>EISSN: 1097-0215</identifier><identifier>DOI: 10.1002/ijc.31335</identifier><identifier>PMID: 29473162</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Adult ; Aged ; Antibodies ; Antigens ; Antigens, Neoplasm - blood ; Antigens, Neoplasm - immunology ; Autoantibodies ; Autoantibodies - immunology ; Biomarkers, Tumor ; CA-125 Antigen ; Cancer ; Cancer and Oncology ; Cancer och onkologi ; Case-Control Studies ; Clinical Medicine ; Diagnosis ; Early detection ; Early Detection of Cancer - methods ; Enzyme-linked immunosorbent assay ; Female ; Health risk assessment ; Humans ; Invasiveness ; Klinisk medicin ; Life Sciences ; Medical and Health Sciences ; Medical research ; Medicin och hälsovetenskap ; Middle Aged ; Ovarian cancer ; Ovarian carcinoma ; Ovarian Neoplasms - blood ; Ovarian Neoplasms - diagnosis ; Ovarian Neoplasms - immunology ; p53 Protein ; Prospective Studies ; Prospective validation ; Proteins ; Risk Factors ; Sensitivity ; Sensitivity and Specificity ; Tumors</subject><ispartof>International journal of cancer, 2018-08, Vol.143 (3), p.515-526</ispartof><rights>2018 UICC</rights><rights>2018 UICC.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5675-a9f1e6cfccb9cb8d42ee733e3e40d6451994f7deba5af3baa734a38df50bf2af3</citedby><cites>FETCH-LOGICAL-c5675-a9f1e6cfccb9cb8d42ee733e3e40d6451994f7deba5af3baa734a38df50bf2af3</cites><orcidid>0000-0003-4661-0763 ; 0000-0003-0674-7757 ; 0000-0003-3751-3929 ; 0000-0002-5558-2437 ; 0000-0001-5256-0163 ; 0000-0003-1441-897X ; 0000-0002-1426-8505 ; 0000-0001-8380-3439 ; 0000-0002-4557-3772</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fijc.31335$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fijc.31335$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,550,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29473162$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-04424802$$DView record in HAL$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-150665$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttps://lup.lub.lu.se/record/1a14e39c-38f1-4587-a4fa-bbecdb8ef2d1$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:138561242$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Kaaks, Rudolf</creatorcontrib><creatorcontrib>Fortner, Renée Turzanski</creatorcontrib><creatorcontrib>Hüsing, Anika</creatorcontrib><creatorcontrib>Barrdahl, Myrto</creatorcontrib><creatorcontrib>Hopper, Marika</creatorcontrib><creatorcontrib>Johnson, Theron</creatorcontrib><creatorcontrib>Tjønneland, Anne</creatorcontrib><creatorcontrib>Hansen, Louise</creatorcontrib><creatorcontrib>Overvad, Kim</creatorcontrib><creatorcontrib>Fournier, Agnès</creatorcontrib><creatorcontrib>Boutron‐Ruault, Marie‐Christine</creatorcontrib><creatorcontrib>Kvaskoff, Marina</creatorcontrib><creatorcontrib>Dossus, Laure</creatorcontrib><creatorcontrib>Johansson, Mattias</creatorcontrib><creatorcontrib>Boeing, Heiner</creatorcontrib><creatorcontrib>Trichopoulou, Antonia</creatorcontrib><creatorcontrib>Benetou, Vassiliki</creatorcontrib><creatorcontrib>La Vecchia, Carlo</creatorcontrib><creatorcontrib>Sieri, Sabina</creatorcontrib><creatorcontrib>Mattiello, Amalia</creatorcontrib><creatorcontrib>Palli, Domenico</creatorcontrib><creatorcontrib>Tumino, Rosario</creatorcontrib><creatorcontrib>Matullo, Giuseppe</creatorcontrib><creatorcontrib>Onland‐Moret, N. Charlotte</creatorcontrib><creatorcontrib>Gram, Inger T.</creatorcontrib><creatorcontrib>Weiderpass, Elisabete</creatorcontrib><creatorcontrib>Sánchez, Maria‐Jose</creatorcontrib><creatorcontrib>Navarro Sanchez, Carmen</creatorcontrib><creatorcontrib>Duell, Eric J.</creatorcontrib><creatorcontrib>Ardanaz, Eva</creatorcontrib><creatorcontrib>Larranaga, Nerea</creatorcontrib><creatorcontrib>Lundin, Eva</creatorcontrib><creatorcontrib>Idahl, Annika</creatorcontrib><creatorcontrib>Jirström, Karin</creatorcontrib><creatorcontrib>Nodin, Björn</creatorcontrib><creatorcontrib>Travis, Ruth C.</creatorcontrib><creatorcontrib>Riboli, Elio</creatorcontrib><creatorcontrib>Merritt, Melissa</creatorcontrib><creatorcontrib>Aune, Dagfinn</creatorcontrib><creatorcontrib>Terry, Kathryn</creatorcontrib><creatorcontrib>Cramer, Daniel W.</creatorcontrib><creatorcontrib>Anderson, Karen S.</creatorcontrib><title>Tumor‐associated autoantibodies as early detection markers for ovarian cancer? A prospective evaluation</title><title>International journal of cancer</title><addtitle>Int J Cancer</addtitle><description>Immuno‐proteomic screening has identified several tumor‐associated autoantibodies (AAb) that may have diagnostic capacity for invasive epithelial ovarian cancer, with AAbs to P53 proteins and cancer‐testis antigens (CTAGs) as prominent examples. However, the early detection potential of these AAbs has been insufficiently explored in prospective studies. We performed ELISA measurements of AAbs to CTAG1A, CTAG2, P53 and NUDT11 proteins, for 194 patients with ovarian cancer and 705 matched controls from the European EPIC cohort, using serum samples collected up to 36 months prior to diagnosis under usual care. CA125 was measured using electrochemo‐luminiscence. Diagnostic discrimination statistics were calculated by strata of lead‐time between blood collection and diagnosis. With lead times ≤6 months, ovarian cancer detection sensitivity at 0.98 specificity (SE98) varied from 0.19 [95% CI 0.08–0.40] for CTAG1A, CTAG2 and NUDT1 to 0.23 [0.10–0.44] for P53 (0.33 [0.11–0.68] for high‐grade serous tumors). However, at longer lead‐times, the ability of these AAb markers to distinguish future ovarian cancer cases from controls declined rapidly; at lead times >1 year, SE98 estimates were close to zero (all invasive cases, range: 0.01–0.11). Compared to CA125 alone, combined logistic regression scores of AAbs and CA125 did not improve detection sensitivity at equal level of specificity. The added value of these selected AAbs as markers for ovarian cancer beyond CA125 for early detection is therefore limited.
What's new?
Could autoantibodies against tumor antigens provide an early warning system for ovarian cancer? These authors tested how well certain antibodies detected ovarian cancer. They selected four candidate antibodies, to p53, CTAG1A, CTAG2 and NUDT11 proteins, which appear in elevated levels in cancer patients. None of them performed well as a herald of burgeoning cancer. They did not perform any better than the best currently available biomarker, CA125, and as lead times increased past 6 months prediagnosis, the effectiveness diminished. Surprisingly, elevated antibodies appeared in quite a few of the control samples, suggesting they might not be as cancer‐specific as expected.</description><subject>Adult</subject><subject>Aged</subject><subject>Antibodies</subject><subject>Antigens</subject><subject>Antigens, Neoplasm - blood</subject><subject>Antigens, Neoplasm - immunology</subject><subject>Autoantibodies</subject><subject>Autoantibodies - immunology</subject><subject>Biomarkers, Tumor</subject><subject>CA-125 Antigen</subject><subject>Cancer</subject><subject>Cancer and Oncology</subject><subject>Cancer och onkologi</subject><subject>Case-Control Studies</subject><subject>Clinical Medicine</subject><subject>Diagnosis</subject><subject>Early detection</subject><subject>Early Detection of Cancer - methods</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Female</subject><subject>Health risk assessment</subject><subject>Humans</subject><subject>Invasiveness</subject><subject>Klinisk medicin</subject><subject>Life Sciences</subject><subject>Medical and Health Sciences</subject><subject>Medical research</subject><subject>Medicin och hälsovetenskap</subject><subject>Middle Aged</subject><subject>Ovarian cancer</subject><subject>Ovarian carcinoma</subject><subject>Ovarian Neoplasms - blood</subject><subject>Ovarian Neoplasms - diagnosis</subject><subject>Ovarian Neoplasms - immunology</subject><subject>p53 Protein</subject><subject>Prospective Studies</subject><subject>Prospective validation</subject><subject>Proteins</subject><subject>Risk Factors</subject><subject>Sensitivity</subject><subject>Sensitivity and Specificity</subject><subject>Tumors</subject><issn>0020-7136</issn><issn>1097-0215</issn><issn>1097-0215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNp9ks1uEzEQx1cIRNPCgRdAK3Eph23ttb0fJxSFjxZF4lK4WmPvGJxu1sFep8qNR-gz8iR4m1ABUjlYtsa_-c9o5p9lLyg5o4SU53alzxhlTDzKZpS0dUFKKh5ns_RHipqy6ig7DmFFCKWC8KfZUdnymtGqnGX2Kq6d__njFkJw2sKIXQ5xdDCMVrnOYsgh5Ai-3-UdjqhH64Z8Df4afciN87nbgrcw5BoGjf5NPs833oXNRG4xxy30EaakZ9kTA33A54f7JPv8_t3V4qJYfvpwuZgvCy2qWhTQGoqVNlqrVqum4yVizRgy5KSruKBty03doQIBhimAmnFgTWcEUaZMoZOs2OuGG9xEJTfepnZ30oGVh9B1eqHkLSkrnvjlg3wfN-modKYECpQja7VkjaGSi6aWwA1IpVB3qkFTdvS_5d_aL3Pp_FcZ11GmVVSVSPzrPf8N-r_gi_lSTjHCeckbUm4n7dM9myb8PWIY5doGjX0PA7oYZElI3TaC3sm--gddueiHNPhEiUaIitZ_FNdpZcGjue-AEjlZSyZryTtrJfblQTGqNXb35G8vJeB8D9zYHncPK8nLj4u95C_rsdtI</recordid><startdate>20180801</startdate><enddate>20180801</enddate><creator>Kaaks, Rudolf</creator><creator>Fortner, Renée Turzanski</creator><creator>Hüsing, Anika</creator><creator>Barrdahl, Myrto</creator><creator>Hopper, Marika</creator><creator>Johnson, Theron</creator><creator>Tjønneland, Anne</creator><creator>Hansen, Louise</creator><creator>Overvad, Kim</creator><creator>Fournier, Agnès</creator><creator>Boutron‐Ruault, Marie‐Christine</creator><creator>Kvaskoff, Marina</creator><creator>Dossus, Laure</creator><creator>Johansson, Mattias</creator><creator>Boeing, Heiner</creator><creator>Trichopoulou, Antonia</creator><creator>Benetou, Vassiliki</creator><creator>La Vecchia, Carlo</creator><creator>Sieri, Sabina</creator><creator>Mattiello, Amalia</creator><creator>Palli, Domenico</creator><creator>Tumino, Rosario</creator><creator>Matullo, Giuseppe</creator><creator>Onland‐Moret, N. Charlotte</creator><creator>Gram, Inger T.</creator><creator>Weiderpass, Elisabete</creator><creator>Sánchez, Maria‐Jose</creator><creator>Navarro Sanchez, Carmen</creator><creator>Duell, Eric J.</creator><creator>Ardanaz, Eva</creator><creator>Larranaga, Nerea</creator><creator>Lundin, Eva</creator><creator>Idahl, Annika</creator><creator>Jirström, Karin</creator><creator>Nodin, Björn</creator><creator>Travis, Ruth C.</creator><creator>Riboli, Elio</creator><creator>Merritt, Melissa</creator><creator>Aune, Dagfinn</creator><creator>Terry, Kathryn</creator><creator>Cramer, Daniel W.</creator><creator>Anderson, Karen S.</creator><general>Wiley Subscription Services, Inc</general><general>Wiley</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>7T5</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D93</scope><scope>D95</scope><scope>D8T</scope><scope>ZZAVC</scope><orcidid>https://orcid.org/0000-0003-4661-0763</orcidid><orcidid>https://orcid.org/0000-0003-0674-7757</orcidid><orcidid>https://orcid.org/0000-0003-3751-3929</orcidid><orcidid>https://orcid.org/0000-0002-5558-2437</orcidid><orcidid>https://orcid.org/0000-0001-5256-0163</orcidid><orcidid>https://orcid.org/0000-0003-1441-897X</orcidid><orcidid>https://orcid.org/0000-0002-1426-8505</orcidid><orcidid>https://orcid.org/0000-0001-8380-3439</orcidid><orcidid>https://orcid.org/0000-0002-4557-3772</orcidid></search><sort><creationdate>20180801</creationdate><title>Tumor‐associated autoantibodies as early detection markers for ovarian cancer? A prospective evaluation</title><author>Kaaks, Rudolf ; Fortner, Renée Turzanski ; Hüsing, Anika ; Barrdahl, Myrto ; Hopper, Marika ; Johnson, Theron ; Tjønneland, Anne ; Hansen, Louise ; Overvad, Kim ; Fournier, Agnès ; Boutron‐Ruault, Marie‐Christine ; Kvaskoff, Marina ; Dossus, Laure ; Johansson, Mattias ; Boeing, Heiner ; Trichopoulou, Antonia ; Benetou, Vassiliki ; La Vecchia, Carlo ; Sieri, Sabina ; Mattiello, Amalia ; Palli, Domenico ; Tumino, Rosario ; Matullo, Giuseppe ; Onland‐Moret, N. Charlotte ; Gram, Inger T. ; Weiderpass, Elisabete ; Sánchez, Maria‐Jose ; Navarro Sanchez, Carmen ; Duell, Eric J. ; Ardanaz, Eva ; Larranaga, Nerea ; Lundin, Eva ; Idahl, Annika ; Jirström, Karin ; Nodin, Björn ; Travis, Ruth C. ; Riboli, Elio ; Merritt, Melissa ; Aune, Dagfinn ; Terry, Kathryn ; Cramer, Daniel W. ; Anderson, Karen S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5675-a9f1e6cfccb9cb8d42ee733e3e40d6451994f7deba5af3baa734a38df50bf2af3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antibodies</topic><topic>Antigens</topic><topic>Antigens, Neoplasm - blood</topic><topic>Antigens, Neoplasm - immunology</topic><topic>Autoantibodies</topic><topic>Autoantibodies - immunology</topic><topic>Biomarkers, Tumor</topic><topic>CA-125 Antigen</topic><topic>Cancer</topic><topic>Cancer and Oncology</topic><topic>Cancer och onkologi</topic><topic>Case-Control Studies</topic><topic>Clinical Medicine</topic><topic>Diagnosis</topic><topic>Early detection</topic><topic>Early Detection of Cancer - methods</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Female</topic><topic>Health risk assessment</topic><topic>Humans</topic><topic>Invasiveness</topic><topic>Klinisk medicin</topic><topic>Life Sciences</topic><topic>Medical and Health Sciences</topic><topic>Medical research</topic><topic>Medicin och hälsovetenskap</topic><topic>Middle Aged</topic><topic>Ovarian cancer</topic><topic>Ovarian carcinoma</topic><topic>Ovarian Neoplasms - blood</topic><topic>Ovarian Neoplasms - diagnosis</topic><topic>Ovarian Neoplasms - immunology</topic><topic>p53 Protein</topic><topic>Prospective Studies</topic><topic>Prospective validation</topic><topic>Proteins</topic><topic>Risk Factors</topic><topic>Sensitivity</topic><topic>Sensitivity and Specificity</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kaaks, Rudolf</creatorcontrib><creatorcontrib>Fortner, Renée Turzanski</creatorcontrib><creatorcontrib>Hüsing, Anika</creatorcontrib><creatorcontrib>Barrdahl, Myrto</creatorcontrib><creatorcontrib>Hopper, Marika</creatorcontrib><creatorcontrib>Johnson, Theron</creatorcontrib><creatorcontrib>Tjønneland, Anne</creatorcontrib><creatorcontrib>Hansen, Louise</creatorcontrib><creatorcontrib>Overvad, Kim</creatorcontrib><creatorcontrib>Fournier, Agnès</creatorcontrib><creatorcontrib>Boutron‐Ruault, Marie‐Christine</creatorcontrib><creatorcontrib>Kvaskoff, Marina</creatorcontrib><creatorcontrib>Dossus, Laure</creatorcontrib><creatorcontrib>Johansson, Mattias</creatorcontrib><creatorcontrib>Boeing, Heiner</creatorcontrib><creatorcontrib>Trichopoulou, Antonia</creatorcontrib><creatorcontrib>Benetou, Vassiliki</creatorcontrib><creatorcontrib>La Vecchia, Carlo</creatorcontrib><creatorcontrib>Sieri, Sabina</creatorcontrib><creatorcontrib>Mattiello, Amalia</creatorcontrib><creatorcontrib>Palli, Domenico</creatorcontrib><creatorcontrib>Tumino, Rosario</creatorcontrib><creatorcontrib>Matullo, Giuseppe</creatorcontrib><creatorcontrib>Onland‐Moret, N. Charlotte</creatorcontrib><creatorcontrib>Gram, Inger T.</creatorcontrib><creatorcontrib>Weiderpass, Elisabete</creatorcontrib><creatorcontrib>Sánchez, Maria‐Jose</creatorcontrib><creatorcontrib>Navarro Sanchez, Carmen</creatorcontrib><creatorcontrib>Duell, Eric J.</creatorcontrib><creatorcontrib>Ardanaz, Eva</creatorcontrib><creatorcontrib>Larranaga, Nerea</creatorcontrib><creatorcontrib>Lundin, Eva</creatorcontrib><creatorcontrib>Idahl, Annika</creatorcontrib><creatorcontrib>Jirström, Karin</creatorcontrib><creatorcontrib>Nodin, Björn</creatorcontrib><creatorcontrib>Travis, Ruth C.</creatorcontrib><creatorcontrib>Riboli, Elio</creatorcontrib><creatorcontrib>Merritt, Melissa</creatorcontrib><creatorcontrib>Aune, Dagfinn</creatorcontrib><creatorcontrib>Terry, Kathryn</creatorcontrib><creatorcontrib>Cramer, Daniel W.</creatorcontrib><creatorcontrib>Anderson, Karen S.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Umeå universitet</collection><collection>SWEPUB Lunds universitet</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>International journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kaaks, Rudolf</au><au>Fortner, Renée Turzanski</au><au>Hüsing, Anika</au><au>Barrdahl, Myrto</au><au>Hopper, Marika</au><au>Johnson, Theron</au><au>Tjønneland, Anne</au><au>Hansen, Louise</au><au>Overvad, Kim</au><au>Fournier, Agnès</au><au>Boutron‐Ruault, Marie‐Christine</au><au>Kvaskoff, Marina</au><au>Dossus, Laure</au><au>Johansson, Mattias</au><au>Boeing, Heiner</au><au>Trichopoulou, Antonia</au><au>Benetou, Vassiliki</au><au>La Vecchia, Carlo</au><au>Sieri, Sabina</au><au>Mattiello, Amalia</au><au>Palli, Domenico</au><au>Tumino, Rosario</au><au>Matullo, Giuseppe</au><au>Onland‐Moret, N. Charlotte</au><au>Gram, Inger T.</au><au>Weiderpass, Elisabete</au><au>Sánchez, Maria‐Jose</au><au>Navarro Sanchez, Carmen</au><au>Duell, Eric J.</au><au>Ardanaz, Eva</au><au>Larranaga, Nerea</au><au>Lundin, Eva</au><au>Idahl, Annika</au><au>Jirström, Karin</au><au>Nodin, Björn</au><au>Travis, Ruth C.</au><au>Riboli, Elio</au><au>Merritt, Melissa</au><au>Aune, Dagfinn</au><au>Terry, Kathryn</au><au>Cramer, Daniel W.</au><au>Anderson, Karen S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tumor‐associated autoantibodies as early detection markers for ovarian cancer? A prospective evaluation</atitle><jtitle>International journal of cancer</jtitle><addtitle>Int J Cancer</addtitle><date>2018-08-01</date><risdate>2018</risdate><volume>143</volume><issue>3</issue><spage>515</spage><epage>526</epage><pages>515-526</pages><issn>0020-7136</issn><issn>1097-0215</issn><eissn>1097-0215</eissn><abstract>Immuno‐proteomic screening has identified several tumor‐associated autoantibodies (AAb) that may have diagnostic capacity for invasive epithelial ovarian cancer, with AAbs to P53 proteins and cancer‐testis antigens (CTAGs) as prominent examples. However, the early detection potential of these AAbs has been insufficiently explored in prospective studies. We performed ELISA measurements of AAbs to CTAG1A, CTAG2, P53 and NUDT11 proteins, for 194 patients with ovarian cancer and 705 matched controls from the European EPIC cohort, using serum samples collected up to 36 months prior to diagnosis under usual care. CA125 was measured using electrochemo‐luminiscence. Diagnostic discrimination statistics were calculated by strata of lead‐time between blood collection and diagnosis. With lead times ≤6 months, ovarian cancer detection sensitivity at 0.98 specificity (SE98) varied from 0.19 [95% CI 0.08–0.40] for CTAG1A, CTAG2 and NUDT1 to 0.23 [0.10–0.44] for P53 (0.33 [0.11–0.68] for high‐grade serous tumors). However, at longer lead‐times, the ability of these AAb markers to distinguish future ovarian cancer cases from controls declined rapidly; at lead times >1 year, SE98 estimates were close to zero (all invasive cases, range: 0.01–0.11). Compared to CA125 alone, combined logistic regression scores of AAbs and CA125 did not improve detection sensitivity at equal level of specificity. The added value of these selected AAbs as markers for ovarian cancer beyond CA125 for early detection is therefore limited.
What's new?
Could autoantibodies against tumor antigens provide an early warning system for ovarian cancer? These authors tested how well certain antibodies detected ovarian cancer. They selected four candidate antibodies, to p53, CTAG1A, CTAG2 and NUDT11 proteins, which appear in elevated levels in cancer patients. None of them performed well as a herald of burgeoning cancer. They did not perform any better than the best currently available biomarker, CA125, and as lead times increased past 6 months prediagnosis, the effectiveness diminished. Surprisingly, elevated antibodies appeared in quite a few of the control samples, suggesting they might not be as cancer‐specific as expected.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>29473162</pmid><doi>10.1002/ijc.31335</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0003-4661-0763</orcidid><orcidid>https://orcid.org/0000-0003-0674-7757</orcidid><orcidid>https://orcid.org/0000-0003-3751-3929</orcidid><orcidid>https://orcid.org/0000-0002-5558-2437</orcidid><orcidid>https://orcid.org/0000-0001-5256-0163</orcidid><orcidid>https://orcid.org/0000-0003-1441-897X</orcidid><orcidid>https://orcid.org/0000-0002-1426-8505</orcidid><orcidid>https://orcid.org/0000-0001-8380-3439</orcidid><orcidid>https://orcid.org/0000-0002-4557-3772</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0020-7136 |
| ispartof | International journal of cancer, 2018-08, Vol.143 (3), p.515-526 |
| issn | 0020-7136 1097-0215 1097-0215 |
| language | eng |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SWEPUB Freely available online |
| subjects | Adult Aged Antibodies Antigens Antigens, Neoplasm - blood Antigens, Neoplasm - immunology Autoantibodies Autoantibodies - immunology Biomarkers, Tumor CA-125 Antigen Cancer Cancer and Oncology Cancer och onkologi Case-Control Studies Clinical Medicine Diagnosis Early detection Early Detection of Cancer - methods Enzyme-linked immunosorbent assay Female Health risk assessment Humans Invasiveness Klinisk medicin Life Sciences Medical and Health Sciences Medical research Medicin och hälsovetenskap Middle Aged Ovarian cancer Ovarian carcinoma Ovarian Neoplasms - blood Ovarian Neoplasms - diagnosis Ovarian Neoplasms - immunology p53 Protein Prospective Studies Prospective validation Proteins Risk Factors Sensitivity Sensitivity and Specificity Tumors |
| title | Tumor‐associated autoantibodies as early detection markers for ovarian cancer? A prospective evaluation |
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