Tryptophan catabolism increases in breast cancer patients compared to healthy controls without affecting the cancer outcome or response to chemotherapy
Abstract Background Indoleamine 2,3-dioxygenase catalyzes the conversion of tryptophan to kynurenine, an immunosuppressive metabolite involved in T regulatory cell differentiation. Indoleamine 2,3-dioxygenase is expressed in many cancer types, including breast cancer. Here, we analyze kynurenine and...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-07-01
|
| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12967-019-1984-2 |
| _version_ | 1818296049077321728 |
|---|---|
| author | Concetta Elisa Onesti François Boemer Claire Josse Stephane Leduc Vincent Bours Guy Jerusalem |
| author_facet | Concetta Elisa Onesti François Boemer Claire Josse Stephane Leduc Vincent Bours Guy Jerusalem |
| author_sort | Concetta Elisa Onesti |
| collection | DOAJ |
| description | Abstract Background Indoleamine 2,3-dioxygenase catalyzes the conversion of tryptophan to kynurenine, an immunosuppressive metabolite involved in T regulatory cell differentiation. Indoleamine 2,3-dioxygenase is expressed in many cancer types, including breast cancer. Here, we analyze kynurenine and tryptophan and their ratio in breast cancer patients and healthy controls. Methods Breast cancer patients and healthy controls were prospectively enrolled in our study. All subjects underwent blood sample withdrawal at diagnosis or on the day of screening mammography for the healthy controls. Plasmatic kynurenine and tryptophan were determined on a TQ5500 tandem mass spectrometer after chromatographic separation. Results We enrolled 146 healthy controls and 202 women with stages I–III breast cancer of all subtypes. All patients underwent surgery, 126 underwent neoadjuvant chemotherapy with 43 showing a pathological complete response, and 43 underwent adjuvant chemotherapy. We observed significantly higher plasmatic kynurenine, tryptophan and their ratio for the healthy controls compared to patients with breast cancer. We observed a lower plasmatic tryptophan and a higher kynurenine/tryptophan ratio in hormone receptor-negative patients compared to hormone receptor-positive cancers. Lobular cancers showed a lower ratio than any other histologies. Advanced cancers were associated with a lower tryptophan level and higher grades with an increased kynurenine/tryptophan ratio. Pathological complete response was associated with higher kynurenine values. The plasmatic kynurenine, tryptophan and kynurenine/tryptophan ratios were not predictive of survival. Conclusions The plasmatic kynurenine, tryptophan and kynurenine/tryptophan ratio could differentiate breast cancer patients from healthy controls. The Kyn/Trp ratio and Trp also showed different values according to hormone receptor status, TNM stage, T grade and histology. These results suggest a rapid metabolism in breast cancer, but no associations with outcome or sensitivity to chemotherapy were observed. |
| first_indexed | 2024-12-13T03:57:21Z |
| format | Article |
| id | doaj.art-7a8a417cd4f148ca8256f59c2c7a3bf9 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-13T03:57:21Z |
| publishDate | 2019-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-7a8a417cd4f148ca8256f59c2c7a3bf92022-12-22T00:00:35ZengBMCJournal of Translational Medicine1479-58762019-07-0117111110.1186/s12967-019-1984-2Tryptophan catabolism increases in breast cancer patients compared to healthy controls without affecting the cancer outcome or response to chemotherapyConcetta Elisa Onesti0François Boemer1Claire Josse2Stephane Leduc3Vincent Bours4Guy Jerusalem5Medical Oncology Department, Centre Hospitalier Universitaire Sart-TilmanDepartment of Human Genetics, Centre Hospitalier Universitaire Sart-TilmanMedical Oncology Department, Centre Hospitalier Universitaire Sart-TilmanDepartment of Human Genetics, Centre Hospitalier Universitaire Sart-TilmanLaboratory of Human Genetics, GIGA Research InstituteMedical Oncology Department, Centre Hospitalier Universitaire Sart-TilmanAbstract Background Indoleamine 2,3-dioxygenase catalyzes the conversion of tryptophan to kynurenine, an immunosuppressive metabolite involved in T regulatory cell differentiation. Indoleamine 2,3-dioxygenase is expressed in many cancer types, including breast cancer. Here, we analyze kynurenine and tryptophan and their ratio in breast cancer patients and healthy controls. Methods Breast cancer patients and healthy controls were prospectively enrolled in our study. All subjects underwent blood sample withdrawal at diagnosis or on the day of screening mammography for the healthy controls. Plasmatic kynurenine and tryptophan were determined on a TQ5500 tandem mass spectrometer after chromatographic separation. Results We enrolled 146 healthy controls and 202 women with stages I–III breast cancer of all subtypes. All patients underwent surgery, 126 underwent neoadjuvant chemotherapy with 43 showing a pathological complete response, and 43 underwent adjuvant chemotherapy. We observed significantly higher plasmatic kynurenine, tryptophan and their ratio for the healthy controls compared to patients with breast cancer. We observed a lower plasmatic tryptophan and a higher kynurenine/tryptophan ratio in hormone receptor-negative patients compared to hormone receptor-positive cancers. Lobular cancers showed a lower ratio than any other histologies. Advanced cancers were associated with a lower tryptophan level and higher grades with an increased kynurenine/tryptophan ratio. Pathological complete response was associated with higher kynurenine values. The plasmatic kynurenine, tryptophan and kynurenine/tryptophan ratios were not predictive of survival. Conclusions The plasmatic kynurenine, tryptophan and kynurenine/tryptophan ratio could differentiate breast cancer patients from healthy controls. The Kyn/Trp ratio and Trp also showed different values according to hormone receptor status, TNM stage, T grade and histology. These results suggest a rapid metabolism in breast cancer, but no associations with outcome or sensitivity to chemotherapy were observed.http://link.springer.com/article/10.1186/s12967-019-1984-2Indoleamine 2,3-dioxygenaseKynurenineTryptophanKynurenine/tryptophan ratioImmune systemBreast cancer |
| spellingShingle | Concetta Elisa Onesti François Boemer Claire Josse Stephane Leduc Vincent Bours Guy Jerusalem Tryptophan catabolism increases in breast cancer patients compared to healthy controls without affecting the cancer outcome or response to chemotherapy Journal of Translational Medicine Indoleamine 2,3-dioxygenase Kynurenine Tryptophan Kynurenine/tryptophan ratio Immune system Breast cancer |
| title | Tryptophan catabolism increases in breast cancer patients compared to healthy controls without affecting the cancer outcome or response to chemotherapy |
| title_full | Tryptophan catabolism increases in breast cancer patients compared to healthy controls without affecting the cancer outcome or response to chemotherapy |
| title_fullStr | Tryptophan catabolism increases in breast cancer patients compared to healthy controls without affecting the cancer outcome or response to chemotherapy |
| title_full_unstemmed | Tryptophan catabolism increases in breast cancer patients compared to healthy controls without affecting the cancer outcome or response to chemotherapy |
| title_short | Tryptophan catabolism increases in breast cancer patients compared to healthy controls without affecting the cancer outcome or response to chemotherapy |
| title_sort | tryptophan catabolism increases in breast cancer patients compared to healthy controls without affecting the cancer outcome or response to chemotherapy |
| topic | Indoleamine 2,3-dioxygenase Kynurenine Tryptophan Kynurenine/tryptophan ratio Immune system Breast cancer |
| url | http://link.springer.com/article/10.1186/s12967-019-1984-2 |
| work_keys_str_mv | AT concettaelisaonesti tryptophancatabolismincreasesinbreastcancerpatientscomparedtohealthycontrolswithoutaffectingthecanceroutcomeorresponsetochemotherapy AT francoisboemer tryptophancatabolismincreasesinbreastcancerpatientscomparedtohealthycontrolswithoutaffectingthecanceroutcomeorresponsetochemotherapy AT clairejosse tryptophancatabolismincreasesinbreastcancerpatientscomparedtohealthycontrolswithoutaffectingthecanceroutcomeorresponsetochemotherapy AT stephaneleduc tryptophancatabolismincreasesinbreastcancerpatientscomparedtohealthycontrolswithoutaffectingthecanceroutcomeorresponsetochemotherapy AT vincentbours tryptophancatabolismincreasesinbreastcancerpatientscomparedtohealthycontrolswithoutaffectingthecanceroutcomeorresponsetochemotherapy AT guyjerusalem tryptophancatabolismincreasesinbreastcancerpatientscomparedtohealthycontrolswithoutaffectingthecanceroutcomeorresponsetochemotherapy |