Tryptophan metabolism enzymes are potential targets in ovarian clear cell carcinoma
Abstract Aim As the second most prevalent subtype of epithelial ovarian cancers, ovarian clear cell carcinoma (OCCC) is known for its chemoresistance to conventional platinum‐based therapy. In this work, we examined the tryptophan (Trp) metabolism enzymes' differential expression in patients wi...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-12-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.6778 |
| _version_ | 1797371942328598528 |
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| author | Sumei Zhang Yike Gao Pan Wang Shu Wang Yuming Wang Mei Li Anqi Wang Kun Zhao Zixin Zhang Jian Sun Dan Guo Zhiyong Liang |
| author_facet | Sumei Zhang Yike Gao Pan Wang Shu Wang Yuming Wang Mei Li Anqi Wang Kun Zhao Zixin Zhang Jian Sun Dan Guo Zhiyong Liang |
| author_sort | Sumei Zhang |
| collection | DOAJ |
| description | Abstract Aim As the second most prevalent subtype of epithelial ovarian cancers, ovarian clear cell carcinoma (OCCC) is known for its chemoresistance to conventional platinum‐based therapy. In this work, we examined the tryptophan (Trp) metabolism enzymes' differential expression in patients with OCCC to assess the potential for personalised treatment. Methods A total of 127 OCCC tissues were used to construct tissue microarrays, and immunohistochemistry (IHC) staining of the Trp enzymes IDO1, IDO2, TDO2 and IL4I1 was performed. The correlations between Trp enzyme expression and clinical characteristics were analysed. Results Positive IDO1, IDO2, TDO2 and IL4I1 staining was identified in 26.8%, 94.5%, 75.6% and 82.7% of OCCC respectively. IDO1‐positive samples were more common in the chemoresistant group than in the platinum‐sensitive group (46.7% vs. 19.8%). Moreover, positive expression of IDO1, TDO2 and IL4I1 was related to advanced stage, metastasis, bilateral tumours, endometriosis and tumour rupture (p < 0.05) respectively. Univariate analysis revealed a significant association between bilateral tumours, lymph node metastasis, advanced stage, distant metastasis and aberrant cytology with a poor prognosis for OCCC, while the absence of residual tumour was correlated with a favourable outcome (p < 0.05). However, only bilateral tumours and lymph node metastases were related to a poor prognosis after multivariate analysis. Conclusion This is the first study to investigate the expression of the Trp enzymes IDO1, IDO2, TDO2 and IL4I1 in OCCC tissues. IDO2, TDO2 and IL4I1 were detected in the majority of OCCC. Clinical traits were correlated with IDO1, IDO2, TDO2 and IL4I1 expression. IDO1 may be used as a therapeutic target given the large percentage of chemoresistant cases with IDO1 expression. These results will aid the development of personalised therapies for OCCC. |
| first_indexed | 2024-03-08T18:28:07Z |
| format | Article |
| id | doaj.art-d61beee2d1e04c3096ad73ccebec3c7c |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-03-08T18:28:07Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-d61beee2d1e04c3096ad73ccebec3c7c2023-12-30T08:53:25ZengWileyCancer Medicine2045-76342023-12-011224219962200510.1002/cam4.6778Tryptophan metabolism enzymes are potential targets in ovarian clear cell carcinomaSumei Zhang0Yike Gao1Pan Wang2Shu Wang3Yuming Wang4Mei Li5Anqi Wang6Kun Zhao7Zixin Zhang8Jian Sun9Dan Guo10Zhiyong Liang11Clinical Biobank, Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing ChinaDepartment of Pathology, Molecular Pathology Research Centre, Peking Union Medical College Hospital Chinese Academy of Medical Science & Peking Union Medical College Beijing ChinaDepartment of Pathology Affiliated Hospital of Hebei University Baoding Hebei Province ChinaDepartment of Obstetrics and Gynaecology, Peking Union Medical College Hospital (PUMCH) Chinese Academy of Medical Sciences & Peking Union Medical College Beijing ChinaDepartment of Pathology, Molecular Pathology Research Centre, Peking Union Medical College Hospital Chinese Academy of Medical Science & Peking Union Medical College Beijing ChinaDepartment of Pathology, Molecular Pathology Research Centre, Peking Union Medical College Hospital Chinese Academy of Medical Science & Peking Union Medical College Beijing ChinaClinical Biobank, Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing ChinaClinical Biobank, Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing ChinaClinical Biobank, Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing ChinaDepartment of Pathology, Molecular Pathology Research Centre, Peking Union Medical College Hospital Chinese Academy of Medical Science & Peking Union Medical College Beijing ChinaClinical Biobank, Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing ChinaDepartment of Pathology, Molecular Pathology Research Centre, Peking Union Medical College Hospital Chinese Academy of Medical Science & Peking Union Medical College Beijing ChinaAbstract Aim As the second most prevalent subtype of epithelial ovarian cancers, ovarian clear cell carcinoma (OCCC) is known for its chemoresistance to conventional platinum‐based therapy. In this work, we examined the tryptophan (Trp) metabolism enzymes' differential expression in patients with OCCC to assess the potential for personalised treatment. Methods A total of 127 OCCC tissues were used to construct tissue microarrays, and immunohistochemistry (IHC) staining of the Trp enzymes IDO1, IDO2, TDO2 and IL4I1 was performed. The correlations between Trp enzyme expression and clinical characteristics were analysed. Results Positive IDO1, IDO2, TDO2 and IL4I1 staining was identified in 26.8%, 94.5%, 75.6% and 82.7% of OCCC respectively. IDO1‐positive samples were more common in the chemoresistant group than in the platinum‐sensitive group (46.7% vs. 19.8%). Moreover, positive expression of IDO1, TDO2 and IL4I1 was related to advanced stage, metastasis, bilateral tumours, endometriosis and tumour rupture (p < 0.05) respectively. Univariate analysis revealed a significant association between bilateral tumours, lymph node metastasis, advanced stage, distant metastasis and aberrant cytology with a poor prognosis for OCCC, while the absence of residual tumour was correlated with a favourable outcome (p < 0.05). However, only bilateral tumours and lymph node metastases were related to a poor prognosis after multivariate analysis. Conclusion This is the first study to investigate the expression of the Trp enzymes IDO1, IDO2, TDO2 and IL4I1 in OCCC tissues. IDO2, TDO2 and IL4I1 were detected in the majority of OCCC. Clinical traits were correlated with IDO1, IDO2, TDO2 and IL4I1 expression. IDO1 may be used as a therapeutic target given the large percentage of chemoresistant cases with IDO1 expression. These results will aid the development of personalised therapies for OCCC.https://doi.org/10.1002/cam4.6778immunohistochemistryovarian clear cell carcinomatryptophan metabolism |
| spellingShingle | Sumei Zhang Yike Gao Pan Wang Shu Wang Yuming Wang Mei Li Anqi Wang Kun Zhao Zixin Zhang Jian Sun Dan Guo Zhiyong Liang Tryptophan metabolism enzymes are potential targets in ovarian clear cell carcinoma Cancer Medicine immunohistochemistry ovarian clear cell carcinoma tryptophan metabolism |
| title | Tryptophan metabolism enzymes are potential targets in ovarian clear cell carcinoma |
| title_full | Tryptophan metabolism enzymes are potential targets in ovarian clear cell carcinoma |
| title_fullStr | Tryptophan metabolism enzymes are potential targets in ovarian clear cell carcinoma |
| title_full_unstemmed | Tryptophan metabolism enzymes are potential targets in ovarian clear cell carcinoma |
| title_short | Tryptophan metabolism enzymes are potential targets in ovarian clear cell carcinoma |
| title_sort | tryptophan metabolism enzymes are potential targets in ovarian clear cell carcinoma |
| topic | immunohistochemistry ovarian clear cell carcinoma tryptophan metabolism |
| url | https://doi.org/10.1002/cam4.6778 |
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