The Expression of the Immunoproteasome Subunit PSMB9 Is Related to Distinct Molecular Subtypes of Uterine Leiomyosarcoma.

BACKGROUND: Uterine leiomyosarcoma (uLMS) are rare and malignant tumors that arise in the myometrium cells and whose diagnosis is based on histopathological features. Identifying diagnostic biomarkers for uLMS is a challenge due to molecular heterogeneity and the scarcity of samples. In vivo and in vitro models for uLMS are urgently needed. Knockout female mice for the catalytic subunit of the immunoproteasome PSMB9 (MIM:177045) develop spontaneous uLMS. This study aimed to analyze the role of PSMB9 in uLMS tumorigenesis and patient outcome. METHODS: Molecular data from 3 non-related uLMS cohorts were integrated and analyzed by proteotranscriptomic using gene expression and protein abundance levels in 68 normal adjacent myometrium (MM), 66 uterine leiomyoma (LM), and 67 uLMS. RESULTS: the immunoproteasome pathway is upregulated and the gene PMSB9 shows heterogeneous expression values in uLMS. Quartile group analysis showed no significant difference between groups high and low PSMB9 expression groups at 3-years overall survival (OS). Using CYBERSORTx analysis we observed 9 out of 17 samples in the high group clustering together due to high M2 macrophages and CD4 memory resting, and high CD8+/PSMB9 ratio was associated with better OS. The main pathway regulated in the high group is IFNγ and in the low is the ECM pathway dependent on the proto-oncogene SRC. CONCLUSION: these findings suggest 2 subtypes of uLMS (immune-related and ECM-related) with different candidate mechanisms of malignancy.

Fertility preservation healthcare circuit and networks in cancer patients worldwide: what are the issues?

BACKGROUND: Fertility preservation (FP) is a major determinant of quality of life after cancer remission for women who may not have achieved their ideal family size. This article describes the FP services and strategy currently available, highlighting issues of oncofertility worldwide. For these patients in complex situations, health networks are essential to improve coordination of care, and the strengthening of this coordination is a major challenge to improve the performance of the health system. Two international networks have been created in order to foster scientific exchange between countries and to standardize the oncofertility healthcare circuit. However, the paucity of referral nationwide networks lead to a structural gap in health care policies. SHORT CONCLUSION: Management strategies of oncofertility in the world are still fragile and uneven. To structure the oncofertility sector, a multidisciplinary project allowing teams to collaborate is of utmost importance particularly in low and middle-income countries.