Tryptophan metabolism enzymes are potential targets in ovarian clear cell carcinoma

Sumei Zhang; Yike Gao; Pan Wang; Shu Wang; Yuming Wang; Mei Li; Anqi Wang; Kun Zhao; Zixin Zhang; Jian Sun; Dan Guo; Zhiyong Liang

doi:10.1002/cam4.6778

Tryptophan metabolism enzymes are potential targets in ovarian clear cell carcinoma

Cancer Med. 2023 Dec;12(24):21996-22005. doi: 10.1002/cam4.6778. Epub 2023 Dec 7.

Authors

Sumei Zhang^{1

2}, Yike Gao³, Pan Wang⁴, Shu Wang^{5

6}, Yuming Wang³, Mei Li³, Anqi Wang^{1

2}, Kun Zhao^{1

2}, Zixin Zhang^{1

2}, Jian Sun³, Dan Guo^{1

2}, Zhiyong Liang³

Affiliations

¹ Clinical Biobank, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
² Department of Medical Research Centre, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
³ Department of Pathology, Molecular Pathology Research Centre, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
⁴ Department of Pathology, Affiliated Hospital of Hebei University, Baoding, Hebei Province, China.
⁵ Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
⁶ National Clinical Research Centre for Obstetric & Gynaecologic Diseases, Beijing, China.

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.

Keywords: immunohistochemistry; ovarian clear cell carcinoma; tryptophan metabolism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Ovarian Epithelial
Female
Humans
L-Amino Acid Oxidase
Ovarian Neoplasms* / pathology
Tryptophan Oxygenase
Tryptophan* / metabolism

Substances

Tryptophan
Tryptophan Oxygenase
IL4I1 protein, human
L-Amino Acid Oxidase

Abstract

Publication types

MeSH terms

Substances

Grants and funding