Proposing a molecular classification associated with hypercoagulation in ovarian clear cell carcinoma

Area of Science:

• Oncology
• Hematology
• Molecular Biology

Background:

• Ovarian clear cell carcinoma (CCC) exhibits a high incidence of thromboembolism, but the significance of hypercoagulable status is not well understood.
• The clinicopathological and biological implications of hypercoagulability in CCC require further investigation.

Purpose of the Study:

• To investigate the prognostic value of D-dimer levels in ovarian clear cell carcinoma (CCC).
• To explore the molecular characteristics and potential subclassifications of CCC based on coagulation status.
• To compare coagulation-related gene profiles in CCC with pan-cancer data.

Main Methods:

• Retrospective analysis of pretreatment D-dimer levels and clinical outcomes in 125 CCC patients (discovery set) and 143 patients (validation sets).
• RNA sequencing of 93 CCCs to compare coagulation-related gene profiles with 2492 pan-cancer samples.
• Investigation of molecular differences in CCC subclasses defined by coagulation status.

Main Results:

• Elevated D-dimer levels in CCC were significantly associated with shorter progression-free and overall survival, independent of thromboembolic status.
• Multivariate analysis identified D-dimer elevation and clinical stage as independent prognostic factors.
• CCC tissues showed higher expression of Tissue Factor and IL6 compared to other cancers; D-dimer elevation correlated with distinct molecular subtypes ('hot' inflammatory vs. 'cold' immune-suppressive tumors).

Conclusions:

• Ovarian clear cell carcinoma (CCC) is characterized by a hypercoagulable state, with elevated D-dimer serving as a prognostic factor for reduced survival.
• CCC with elevated D-dimer exhibits distinct molecular profiles, including inflammatory ('hot') and immune-suppressive ('cold') tumor subtypes.
• The proposed molecular classification warrants further investigation for potential treatment implications.