ERCC1-expressing circulating tumor cells as a potential diagnostic tool for monitoring response to platinum-based chemotherapy and for predicting post-therapeutic outcome of ovarian cancer
We recently showed that the presence of ERCC1+CTCs is an independent predictive biomarker for platinum-resistance and poor prognosis of ovarian cancer. The goal of our current research was to determine how the auxiliary assessment of ERCC1-transcripts influences overall CTC-detection rate. We extend...
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| Veröffentlicht in: | Oncotarget 2017-04, Vol.8 (15), p.24303-24313 |
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| creator | Chebouti, Issam Kuhlmann, Jan Dominik Buderath, Paul Weber, Stephan Wimberger, Pauline Bokeloh, Yvonne Hauch, Siegfried Kimmig, Rainer Kasimir-Bauer, Sabine |
| description | We recently showed that the presence of ERCC1+CTCs is an independent predictive biomarker for platinum-resistance and poor prognosis of ovarian cancer. The goal of our current research was to determine how the auxiliary assessment of ERCC1-transcripts influences overall CTC-detection rate. We extended this investigation from an initially predictive setting to paired pre- and post-therapeutic blood analysis in order to see, whether ERCC1+CTCs dynamics mirror response to chemotherapy.
65 Paired blood samples (10ml) of primary ovarian cancer patients at primary diagnosis and after chemotherapy were studied for CTCs with the AdnaTest Ovarian Cancer (QIAGEN Hannover GmbH). We analyzed the tumor-associated transcripts EpCAM, MUC-1 and CA-125. ERCC1-transcripts were investigated in a separate approach by singleplex RT-PCR.
Auxiliary assessment of ERCC1-transcripts enhanced the overall CTC-detection rate up to 17%. ERCC1+CTCs (defined as positive for one of the AdnaTest markers plus ERCC1-positivity) were detected in 15% of patients at primary diagnosis and in 12% after chemotherapy. The presence of ERCC1+CTCs after chemotherapy correlated with platinum-resistance (P=0.01), reduced PFS (P=0.0293) and OS (P=0.0008) and their persistence indicated poor post-therapeutic outcome (PFS: P=0.005; OS: P=0.0058). Interestingly, the assessment of ERCC1-transcripts alone was sufficient for the detection of prognostic relevant ERCC1-expressing CTCs.
Auxiliary assessment of ERCC1-transcripts expands the phenotypic spectrum of CTC detection and defines an additional overlapping fraction of ERCC1-expressing CTCs, which are potentially selected by platinum-based chemotherapy. Specifically, we suggest that ERCC1+CTCs could additionally be useful as a surrogate for monitoring platinum-based chemotherapy and to assess the post-therapeutic outcome of ovarian cancer. |
| doi_str_mv | 10.18632/oncotarget.13286 |
| format | Article |
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65 Paired blood samples (10ml) of primary ovarian cancer patients at primary diagnosis and after chemotherapy were studied for CTCs with the AdnaTest Ovarian Cancer (QIAGEN Hannover GmbH). We analyzed the tumor-associated transcripts EpCAM, MUC-1 and CA-125. ERCC1-transcripts were investigated in a separate approach by singleplex RT-PCR.
Auxiliary assessment of ERCC1-transcripts enhanced the overall CTC-detection rate up to 17%. ERCC1+CTCs (defined as positive for one of the AdnaTest markers plus ERCC1-positivity) were detected in 15% of patients at primary diagnosis and in 12% after chemotherapy. The presence of ERCC1+CTCs after chemotherapy correlated with platinum-resistance (P=0.01), reduced PFS (P=0.0293) and OS (P=0.0008) and their persistence indicated poor post-therapeutic outcome (PFS: P=0.005; OS: P=0.0058). Interestingly, the assessment of ERCC1-transcripts alone was sufficient for the detection of prognostic relevant ERCC1-expressing CTCs.
Auxiliary assessment of ERCC1-transcripts expands the phenotypic spectrum of CTC detection and defines an additional overlapping fraction of ERCC1-expressing CTCs, which are potentially selected by platinum-based chemotherapy. Specifically, we suggest that ERCC1+CTCs could additionally be useful as a surrogate for monitoring platinum-based chemotherapy and to assess the post-therapeutic outcome of ovarian cancer.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.13286</identifier><identifier>PMID: 28388557</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biomarkers, Tumor - biosynthesis ; Biomarkers, Tumor - blood ; DNA-Binding Proteins - biosynthesis ; DNA-Binding Proteins - blood ; DNA-Binding Proteins - genetics ; Endonucleases - biosynthesis ; Endonucleases - blood ; Endonucleases - genetics ; Female ; Humans ; Middle Aged ; Neoplastic Cells, Circulating - metabolism ; Neoplastic Cells, Circulating - pathology ; Organoplatinum Compounds - administration & dosage ; Ovarian Neoplasms - blood ; Ovarian Neoplasms - drug therapy ; Ovarian Neoplasms - genetics ; Ovarian Neoplasms - pathology ; Predictive Value of Tests ; Prognosis ; Research Paper ; Treatment Outcome</subject><ispartof>Oncotarget, 2017-04, Vol.8 (15), p.24303-24313</ispartof><rights>Copyright: © 2017 Chebouti et al. 2017</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-4097d3778ba0f98a11380f6eb4c8ec4b20ac5d47ce4af3412f31b18cea68f4163</citedby><cites>FETCH-LOGICAL-c422t-4097d3778ba0f98a11380f6eb4c8ec4b20ac5d47ce4af3412f31b18cea68f4163</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/PMC5421848/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421848/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28388557$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chebouti, Issam</creatorcontrib><creatorcontrib>Kuhlmann, Jan Dominik</creatorcontrib><creatorcontrib>Buderath, Paul</creatorcontrib><creatorcontrib>Weber, Stephan</creatorcontrib><creatorcontrib>Wimberger, Pauline</creatorcontrib><creatorcontrib>Bokeloh, Yvonne</creatorcontrib><creatorcontrib>Hauch, Siegfried</creatorcontrib><creatorcontrib>Kimmig, Rainer</creatorcontrib><creatorcontrib>Kasimir-Bauer, Sabine</creatorcontrib><title>ERCC1-expressing circulating tumor cells as a potential diagnostic tool for monitoring response to platinum-based chemotherapy and for predicting post-therapeutic outcome of ovarian cancer</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>We recently showed that the presence of ERCC1+CTCs is an independent predictive biomarker for platinum-resistance and poor prognosis of ovarian cancer. The goal of our current research was to determine how the auxiliary assessment of ERCC1-transcripts influences overall CTC-detection rate. We extended this investigation from an initially predictive setting to paired pre- and post-therapeutic blood analysis in order to see, whether ERCC1+CTCs dynamics mirror response to chemotherapy.
65 Paired blood samples (10ml) of primary ovarian cancer patients at primary diagnosis and after chemotherapy were studied for CTCs with the AdnaTest Ovarian Cancer (QIAGEN Hannover GmbH). We analyzed the tumor-associated transcripts EpCAM, MUC-1 and CA-125. ERCC1-transcripts were investigated in a separate approach by singleplex RT-PCR.
Auxiliary assessment of ERCC1-transcripts enhanced the overall CTC-detection rate up to 17%. ERCC1+CTCs (defined as positive for one of the AdnaTest markers plus ERCC1-positivity) were detected in 15% of patients at primary diagnosis and in 12% after chemotherapy. The presence of ERCC1+CTCs after chemotherapy correlated with platinum-resistance (P=0.01), reduced PFS (P=0.0293) and OS (P=0.0008) and their persistence indicated poor post-therapeutic outcome (PFS: P=0.005; OS: P=0.0058). Interestingly, the assessment of ERCC1-transcripts alone was sufficient for the detection of prognostic relevant ERCC1-expressing CTCs.
Auxiliary assessment of ERCC1-transcripts expands the phenotypic spectrum of CTC detection and defines an additional overlapping fraction of ERCC1-expressing CTCs, which are potentially selected by platinum-based chemotherapy. Specifically, we suggest that ERCC1+CTCs could additionally be useful as a surrogate for monitoring platinum-based chemotherapy and to assess the post-therapeutic outcome of ovarian cancer.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biomarkers, Tumor - biosynthesis</subject><subject>Biomarkers, Tumor - blood</subject><subject>DNA-Binding Proteins - biosynthesis</subject><subject>DNA-Binding Proteins - blood</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Endonucleases - biosynthesis</subject><subject>Endonucleases - blood</subject><subject>Endonucleases - genetics</subject><subject>Female</subject><subject>Humans</subject><subject>Middle Aged</subject><subject>Neoplastic Cells, Circulating - metabolism</subject><subject>Neoplastic Cells, Circulating - pathology</subject><subject>Organoplatinum Compounds - administration & dosage</subject><subject>Ovarian Neoplasms - blood</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Predictive Value of Tests</subject><subject>Prognosis</subject><subject>Research Paper</subject><subject>Treatment Outcome</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkc1q3TAQhU1paUKaB-imaNmNU-vH1_KmUC7pDwQKpV2LsTy-V8XWuJIcmnfLw1X2TdNUCDQwc74j5hTFa15dcb2T4h15SwnCAdMVl0LvnhXnvFVtKepaPn9SnxWXMf6s8qlVo0X7sjgTWmpd1815cX_9bb_nJf6eA8bo_IFZF-wyQlrrtEwUmMVxjAzyZTMl9MnByHoHB08xOcsS0ciGPDiRd4nCqsy0mXzE3GTzRlumsoOIPbNHnCgdMcB8x8D3mzTb985upnOmlqc-LiuflmRpQkYDo1sIDjyz4C2GV8WLAcaIlw_vRfHj4_X3_efy5uunL_sPN6VVQqRSVW3Ty6bRHVRDq4Fzqathh52yGq3qRAW27lVjUcEgFReD5B3XFmGnB8V38qJ4f-LOSzdhb_MKAoxmDm6CcGcInPm_493RHOjW1EpwrXQGvH0ABPq1YExmcnFdK3ikJRqe02hVLZt1lJ9GbaAYAw6PNrwyW_DmX_BmCz5r3jz936Pib8zyDxZJs9E</recordid><startdate>20170411</startdate><enddate>20170411</enddate><creator>Chebouti, Issam</creator><creator>Kuhlmann, Jan Dominik</creator><creator>Buderath, Paul</creator><creator>Weber, Stephan</creator><creator>Wimberger, Pauline</creator><creator>Bokeloh, Yvonne</creator><creator>Hauch, Siegfried</creator><creator>Kimmig, Rainer</creator><creator>Kasimir-Bauer, Sabine</creator><general>Impact Journals LLC</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170411</creationdate><title>ERCC1-expressing circulating tumor cells as a potential diagnostic tool for monitoring response to platinum-based chemotherapy and for predicting post-therapeutic outcome of ovarian cancer</title><author>Chebouti, Issam ; Kuhlmann, Jan Dominik ; Buderath, Paul ; Weber, Stephan ; Wimberger, Pauline ; Bokeloh, Yvonne ; Hauch, Siegfried ; Kimmig, Rainer ; Kasimir-Bauer, Sabine</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-4097d3778ba0f98a11380f6eb4c8ec4b20ac5d47ce4af3412f31b18cea68f4163</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>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Biomarkers, Tumor - biosynthesis</topic><topic>Biomarkers, Tumor - blood</topic><topic>DNA-Binding Proteins - biosynthesis</topic><topic>DNA-Binding Proteins - blood</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Endonucleases - biosynthesis</topic><topic>Endonucleases - blood</topic><topic>Endonucleases - genetics</topic><topic>Female</topic><topic>Humans</topic><topic>Middle Aged</topic><topic>Neoplastic Cells, Circulating - metabolism</topic><topic>Neoplastic Cells, Circulating - pathology</topic><topic>Organoplatinum Compounds - administration & dosage</topic><topic>Ovarian Neoplasms - blood</topic><topic>Ovarian Neoplasms - drug therapy</topic><topic>Ovarian Neoplasms - genetics</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Predictive Value of Tests</topic><topic>Prognosis</topic><topic>Research Paper</topic><topic>Treatment Outcome</topic><toplevel>online_resources</toplevel><creatorcontrib>Chebouti, Issam</creatorcontrib><creatorcontrib>Kuhlmann, Jan Dominik</creatorcontrib><creatorcontrib>Buderath, Paul</creatorcontrib><creatorcontrib>Weber, Stephan</creatorcontrib><creatorcontrib>Wimberger, Pauline</creatorcontrib><creatorcontrib>Bokeloh, Yvonne</creatorcontrib><creatorcontrib>Hauch, Siegfried</creatorcontrib><creatorcontrib>Kimmig, Rainer</creatorcontrib><creatorcontrib>Kasimir-Bauer, Sabine</creatorcontrib><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>PubMed Central (Full Participant titles)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chebouti, Issam</au><au>Kuhlmann, Jan Dominik</au><au>Buderath, Paul</au><au>Weber, Stephan</au><au>Wimberger, Pauline</au><au>Bokeloh, Yvonne</au><au>Hauch, Siegfried</au><au>Kimmig, Rainer</au><au>Kasimir-Bauer, Sabine</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ERCC1-expressing circulating tumor cells as a potential diagnostic tool for monitoring response to platinum-based chemotherapy and for predicting post-therapeutic outcome of ovarian cancer</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2017-04-11</date><risdate>2017</risdate><volume>8</volume><issue>15</issue><spage>24303</spage><epage>24313</epage><pages>24303-24313</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>We recently showed that the presence of ERCC1+CTCs is an independent predictive biomarker for platinum-resistance and poor prognosis of ovarian cancer. The goal of our current research was to determine how the auxiliary assessment of ERCC1-transcripts influences overall CTC-detection rate. We extended this investigation from an initially predictive setting to paired pre- and post-therapeutic blood analysis in order to see, whether ERCC1+CTCs dynamics mirror response to chemotherapy.
65 Paired blood samples (10ml) of primary ovarian cancer patients at primary diagnosis and after chemotherapy were studied for CTCs with the AdnaTest Ovarian Cancer (QIAGEN Hannover GmbH). We analyzed the tumor-associated transcripts EpCAM, MUC-1 and CA-125. ERCC1-transcripts were investigated in a separate approach by singleplex RT-PCR.
Auxiliary assessment of ERCC1-transcripts enhanced the overall CTC-detection rate up to 17%. ERCC1+CTCs (defined as positive for one of the AdnaTest markers plus ERCC1-positivity) were detected in 15% of patients at primary diagnosis and in 12% after chemotherapy. The presence of ERCC1+CTCs after chemotherapy correlated with platinum-resistance (P=0.01), reduced PFS (P=0.0293) and OS (P=0.0008) and their persistence indicated poor post-therapeutic outcome (PFS: P=0.005; OS: P=0.0058). Interestingly, the assessment of ERCC1-transcripts alone was sufficient for the detection of prognostic relevant ERCC1-expressing CTCs.
Auxiliary assessment of ERCC1-transcripts expands the phenotypic spectrum of CTC detection and defines an additional overlapping fraction of ERCC1-expressing CTCs, which are potentially selected by platinum-based chemotherapy. Specifically, we suggest that ERCC1+CTCs could additionally be useful as a surrogate for monitoring platinum-based chemotherapy and to assess the post-therapeutic outcome of ovarian cancer.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>28388557</pmid><doi>10.18632/oncotarget.13286</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biomarkers, Tumor - biosynthesis Biomarkers, Tumor - blood DNA-Binding Proteins - biosynthesis DNA-Binding Proteins - blood DNA-Binding Proteins - genetics Endonucleases - biosynthesis Endonucleases - blood Endonucleases - genetics Female Humans Middle Aged Neoplastic Cells, Circulating - metabolism Neoplastic Cells, Circulating - pathology Organoplatinum Compounds - administration & dosage Ovarian Neoplasms - blood Ovarian Neoplasms - drug therapy Ovarian Neoplasms - genetics Ovarian Neoplasms - pathology Predictive Value of Tests Prognosis Research Paper Treatment Outcome |
| title | ERCC1-expressing circulating tumor cells as a potential diagnostic tool for monitoring response to platinum-based chemotherapy and for predicting post-therapeutic outcome of ovarian cancer |
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