open access: The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation (references major epithelial OC cell types including clear cell)

Background

The neural transcription factor SOX11 has been described as a prognostic marker in epithelial ovarian cancers (EOC), however its role in individual histological subtypes and tumour grade requires further clarification. Furthermore, methylation-dependent silencing of SOX11 has been reported for B cell lymphomas and indicates that epigenetic drugs may be used to re-express this tumour suppressor, but information on SOX11 promoter methylation in EOC is still lacking.

Results

SOX11 expression was associated with an improved survival of patients with high grade EOC, although not independent of stage.

 

"SOX11 is a diagnostic and prognostic antigen in B cell lymphomas [12-17] and has recently been demonstrated by us to have tumour suppressor functions [18]. This transcription factor is also a prognostic antigen in EOC, where its presence is associated with improved recurrence-free survival (RFS) [19]. In the present study, we confirm the relationship between SOX11 and survival in EOC, although a larger set of endometrioid cancer needs to be investigated to show independent prognostic relevance."

 

Conclusions:

In the present study, SOX11 was demonstrated to be of prognostic value for high grade EOC, which could have a clear clinical value. The possibility to re-express SOX11 indicates a potential use of epigenetic drugs to affect cell growth through common cell regulatory pathways, controlled by SOX11, and other tumour suppressors that are silenced in EOC. 

 

Furthermore, functional investigations in vitro confirmed a growth regulatory role for SOX11 in EOC.

 

Competing interests

A patent has been filed on the use of SOX11 as a diagnostic and prognostic antigen in EOC.

Methylation profiles of hereditary and sporadic ovarian cancer - Histopathology - abstract

Conclusions: 

 CDH13, GSTP1 and RASSF1 are frequently methylated in both sporadic and BRCA1-associated ovarian cancers. Interestingly, methylation of BRCA1, while frequent in sporadic ovarian cancer, never occurred in the hereditary group. BRCA1-associated ovarian cancers mimic their sporadic counterparts in extent and pattern of promoter methylation of several common tumour suppressor genes. This finding could have implications for future chemotherapy regimens based on epigenetic changes

Cancer epigenomics: Implications of DNA methylation in personalized cancer therapy - Cancer Science

Note: in research; see Table 1 for references to ovarian cancer/cisplatin

"Methylation of FANCF has been found in 20% of primary ovarian cancers not previously exposed to cisplatin, but the correlation between chemosensitivity and FANCF methylation in primary tumors remains to be determined."