OPEN Research Support

Louise Faaborg
Department of Oncology, Vejle Hospital

Projekt styring
Projekt status    Sampling ongoing
Data indsamlingsdatoer
Start 01.05.2016  
Slut 28.02.2022  

The predictive value of HOXA9 methylation in ovarian cancer patients undergoing palliative treatment for recurrence of disease

Short summary

Despite response to chemotherapy around 80% of patients with ovarian cancer (OC) will experience recurrence of disease, which is incurable in almost all cases. 

The aim of this study is to analyse and monitor HOXA9 methylated circulating tumor DNA (ctDNA) in patients with recurrence of disease, with the perspective to identify patients who can benefit from palliative chemotherapy.


Ovarian cancer (OC) remains the most lethal disease among gynecological malignancies. The majority of patients are diagnosed in an advanced stage and exhibit resistance to standard chemotherapy. 

The treatment of OC is primary surgical debulking followed by adjuvant chemotherapy or neoadjuvant chemotherapy and interval debulking surgery followed by chemotherapy in around 50%.

By this approach 60-80% of patients will achieve clinical complete or partial response. However, 70-80% of the patients will experience recurrence of disease, most within two years after completion of chemotherapy. 

Recurrent OC is an incurable disease in almost all cases and leaves the patients with few or no treatment options, often after several chemotherapy regimens.

Potential biomarkers that could contribute to the management of OC by monitoring response to treatment, detecting recurrence, distinguishing benign from malignant pelvic masses and attempting to detect disease at an earlier stage has therefore been of major interest, but no reliable marker has been found yet. The currently used biomarker CA125 does not meet the criteria of an ideal marker as both the sensitivity and specificity is poor and a large proportion of OC has little or no expression of CA125.

Aberrant DNA methylation in ovarian cancer is observed in early cancer development. It can be detected in circulating tumor DNA (ctDNA) in the blood and hence provides the promise of a non-invasive detection test. 

The HOX gene HOXA9 has especially been associated with OC. This gene is normally expressed during differentiation of the Müllerian ducts into the female reproductive tract during embryogenesis. HOXA9 promoter methylation has been observed in a large proportion of patients with high grade serous OC and methylation of HOXA9 is associated with poorer outcome. The clinical potential of HOXA9 is however, not well investigated.

Study hypotheses:

• HOXA9 methylation can be used as a prognostic factor during palliative treatment in patients with recurrence of OC.

• Patients without or with low levels of methylated HOXA9 in plasma do better compared to patients where HOXA9 converts to a methylated status while undergoing treatment or patients with unchanged high levels of HOXA9 during treatment.

The purpose is to analyse and monitor HOXA9 methylation in patients with recurrence of disease, with the perspective to identify patients who can benefit from palliative chemotherapy. 

The study will challenge the hypothesis, that change from methylated to un-methylated status of HOXA9 in plasma is an important prognostic factor. The study will also investigate the prognostic importance of quantitative methylated HOXA9 ctDNA.

Description of the cohort

The study is an open prospective study and includes patients with relapse of OC (all stages), who are offered palliative chemotherapy of any kind at the Department of Oncology, Vejle Hospital. 

Data and biological material


The blood samples will be drawn before start of palliative chemotherapy of any kind, 15 days after the first cycle and at every cycle until progression or stop of treatment for other reasons. The sampling schedule follows the standard procedure in the department.

Collaborating researchers and departments

Department of Oncology, Vejle Hospital

  • Professor, PhD, MD, Karina Dahl Steffensen 

Department of Pathology, Vejle Hospital

  • MD, MPM, Marianne Waldstrøm

Department of Biochemistry and Immunology, Vejle Hospital

  • Molecular biologist, PhD, Rikke Fredslund Andersen