Elevated doublecortin-like kinase 1 serum levels revert to baseline after therapy in early stage esophageal adenocarcinoma
Abstract Background Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) incidence has been increasing in the United States for greater than 30 years. For the majority of EAC patients, treatment is limited and prognosis poor. Doublecortin like kinase-1 (DCLK1) is a cancer stem cell marker wi...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-03-01
|
| Series: | Biomarker Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40364-019-0157-z |
| _version_ | 1819212726032924672 |
|---|---|
| author | Emily M. Christman Parthasarathy Chandrakesan Nathaniel Weygant John T. Maple William M. Tierney Kenneth J. Vega Courtney W. Houchen |
| author_facet | Emily M. Christman Parthasarathy Chandrakesan Nathaniel Weygant John T. Maple William M. Tierney Kenneth J. Vega Courtney W. Houchen |
| author_sort | Emily M. Christman |
| collection | DOAJ |
| description | Abstract Background Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) incidence has been increasing in the United States for greater than 30 years. For the majority of EAC patients, treatment is limited and prognosis poor. Doublecortin like kinase-1 (DCLK1) is a cancer stem cell marker with elevated expression in BE patients with high grade dysplasia and/or EAC. This prospective cohort study was designed to compare serum DCLK1 levels before and after EAC treatment with endoscopic mucosal resection (EMR) and/or radio-frequency ablation (RFA). Methods Barrett’s esophagus patients with low or high-grade dysplasia (n = 9) and EAC patients (Stage I/II) eligible for treatment were enrolled (n = 14). Serum was obtained at enrollment and at end of treatment (EoT) where possible (n = 6). Normal control samples (n = 5) were obtained from patients with normal upper endoscopies. Serum was analyzed for DCLK1 protein content by ELISA. Kruskal-Wallis, Mann Whitney U, Pearson correlation, and Receiver Operating Characteristic tests were used to analyze the data. Results Serum DCLK1 levels were increased by > 50% in Barrett’s Esophagus (n = 9) and EAC patients (n = 14) vs controls (n = 5, p = 0.0007). These levels were reduced > 50% at EoT compared to EAC (p = 0.033). Although age was significantly lower in controls, this factor was not statistically related to DCLK1 serum levels (p = 0.66). Conclusions EAC treatment results in significantly decreased serum DCLK1 levels, suggesting that DCLK1 may be useful as a non-invasive disease regression biomarker following treatment. Impact Biomarkers for EAC therapeutic response have been poorly studied and no reliable marker has been discovered thus far. These results demonstrate that DCLK1 may have potential as a circulating biomarker of the response to therapy in EAC, which could be used to improve patient outcomes. |
| first_indexed | 2024-12-23T06:47:32Z |
| format | Article |
| id | doaj.art-b5557fca45764624b93dfe0f98caa7ff |
| institution | Directory Open Access Journal |
| issn | 2050-7771 |
| language | English |
| last_indexed | 2024-12-23T06:47:32Z |
| publishDate | 2019-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Biomarker Research |
| spelling | doaj.art-b5557fca45764624b93dfe0f98caa7ff2022-12-21T17:56:31ZengBMCBiomarker Research2050-77712019-03-01711510.1186/s40364-019-0157-zElevated doublecortin-like kinase 1 serum levels revert to baseline after therapy in early stage esophageal adenocarcinomaEmily M. Christman0Parthasarathy Chandrakesan1Nathaniel Weygant2John T. Maple3William M. Tierney4Kenneth J. Vega5Courtney W. Houchen6Department of Medicine, University of Oklahoma Health Sciences CenterDepartment of Medicine, University of Oklahoma Health Sciences CenterDepartment of Medicine, University of Oklahoma Health Sciences CenterDepartment of Medicine, University of Oklahoma Health Sciences CenterDepartment of Medicine, University of Oklahoma Health Sciences CenterDepartment of Medicine, Division of Gastroenterology and Hepatology, Augusta University-Medical College of GeorgiaDepartment of Medicine, University of Oklahoma Health Sciences CenterAbstract Background Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) incidence has been increasing in the United States for greater than 30 years. For the majority of EAC patients, treatment is limited and prognosis poor. Doublecortin like kinase-1 (DCLK1) is a cancer stem cell marker with elevated expression in BE patients with high grade dysplasia and/or EAC. This prospective cohort study was designed to compare serum DCLK1 levels before and after EAC treatment with endoscopic mucosal resection (EMR) and/or radio-frequency ablation (RFA). Methods Barrett’s esophagus patients with low or high-grade dysplasia (n = 9) and EAC patients (Stage I/II) eligible for treatment were enrolled (n = 14). Serum was obtained at enrollment and at end of treatment (EoT) where possible (n = 6). Normal control samples (n = 5) were obtained from patients with normal upper endoscopies. Serum was analyzed for DCLK1 protein content by ELISA. Kruskal-Wallis, Mann Whitney U, Pearson correlation, and Receiver Operating Characteristic tests were used to analyze the data. Results Serum DCLK1 levels were increased by > 50% in Barrett’s Esophagus (n = 9) and EAC patients (n = 14) vs controls (n = 5, p = 0.0007). These levels were reduced > 50% at EoT compared to EAC (p = 0.033). Although age was significantly lower in controls, this factor was not statistically related to DCLK1 serum levels (p = 0.66). Conclusions EAC treatment results in significantly decreased serum DCLK1 levels, suggesting that DCLK1 may be useful as a non-invasive disease regression biomarker following treatment. Impact Biomarkers for EAC therapeutic response have been poorly studied and no reliable marker has been discovered thus far. These results demonstrate that DCLK1 may have potential as a circulating biomarker of the response to therapy in EAC, which could be used to improve patient outcomes.http://link.springer.com/article/10.1186/s40364-019-0157-zDCLK1Doublecortin-like kinase 1Esophageal adenocarcinomaCancer stem cellELISA |
| spellingShingle | Emily M. Christman Parthasarathy Chandrakesan Nathaniel Weygant John T. Maple William M. Tierney Kenneth J. Vega Courtney W. Houchen Elevated doublecortin-like kinase 1 serum levels revert to baseline after therapy in early stage esophageal adenocarcinoma Biomarker Research DCLK1 Doublecortin-like kinase 1 Esophageal adenocarcinoma Cancer stem cell ELISA |
| title | Elevated doublecortin-like kinase 1 serum levels revert to baseline after therapy in early stage esophageal adenocarcinoma |
| title_full | Elevated doublecortin-like kinase 1 serum levels revert to baseline after therapy in early stage esophageal adenocarcinoma |
| title_fullStr | Elevated doublecortin-like kinase 1 serum levels revert to baseline after therapy in early stage esophageal adenocarcinoma |
| title_full_unstemmed | Elevated doublecortin-like kinase 1 serum levels revert to baseline after therapy in early stage esophageal adenocarcinoma |
| title_short | Elevated doublecortin-like kinase 1 serum levels revert to baseline after therapy in early stage esophageal adenocarcinoma |
| title_sort | elevated doublecortin like kinase 1 serum levels revert to baseline after therapy in early stage esophageal adenocarcinoma |
| topic | DCLK1 Doublecortin-like kinase 1 Esophageal adenocarcinoma Cancer stem cell ELISA |
| url | http://link.springer.com/article/10.1186/s40364-019-0157-z |
| work_keys_str_mv | AT emilymchristman elevateddoublecortinlikekinase1serumlevelsreverttobaselineaftertherapyinearlystageesophagealadenocarcinoma AT parthasarathychandrakesan elevateddoublecortinlikekinase1serumlevelsreverttobaselineaftertherapyinearlystageesophagealadenocarcinoma AT nathanielweygant elevateddoublecortinlikekinase1serumlevelsreverttobaselineaftertherapyinearlystageesophagealadenocarcinoma AT johntmaple elevateddoublecortinlikekinase1serumlevelsreverttobaselineaftertherapyinearlystageesophagealadenocarcinoma AT williammtierney elevateddoublecortinlikekinase1serumlevelsreverttobaselineaftertherapyinearlystageesophagealadenocarcinoma AT kennethjvega elevateddoublecortinlikekinase1serumlevelsreverttobaselineaftertherapyinearlystageesophagealadenocarcinoma AT courtneywhouchen elevateddoublecortinlikekinase1serumlevelsreverttobaselineaftertherapyinearlystageesophagealadenocarcinoma |