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Published on: August 2, 2024
Low RAP80 mRNA expression correlates with shorter survival in sporadic high-grade serous ovarian carcinoma
Margarita Romeo1,2, Niki Karachaliou3, Imane Chaid4
1Medical Oncology Department, Catalan Institute of Oncology, Badalona - Spain.
Objective:
Homologous recombination (HR) is frequently impaired in sporadic high-grade serous ovarian carcinoma (sHGSOC) due to deficiencies in BRCA1/2 genes, a situation associated with hypersensitivity to platinum compounds. Alterations in other genes can also cause HR deficiency. Preclinical data show that RAP80 is an HR-pathway-related gene that influences BRCA1 activity. RAP80 has been reported to affect outcome in some solid neoplasms. This study investigates the role of RAP80 in sHGSOC survival.
Methods:
mRNA expression of RAP80 was analyzed in tumor samples from 35 patients who postoperatively received standard platinum-based chemotherapy. The effects of RAP80 expression on progression-free survival (PFS) and overall survival (OS) were examined by means of Cox regressions. The clinical variables known to have prognostic value (FIGO stage, residual disease at surgery, and debulking surgery) were included as covariates in the analysis. BRCA1 was analyzed given the moderate correlations with RAP80.
Results:
Median follow-up, PFS and OS were 61.3, 20.2 and 62.8 months, respectively. Low RAP80 expression levels were associated with shorter PFS (HR = 1.449, p = 0.007) and OS (HR = 1.331, p = 0.047).
Conclusions:
This is the first study to show a potential prognostic role of RAP80 expression in patients with HGSOC. The results suggest that HR deficiency due to low RAP80 expression is not associated with hypersensitivity to platinum compounds in sHGSOC.
Insights
Low RAP80 expression in high-grade serous ovarian carcinoma (HGSOC) correlates with shorter survival. This suggests RAP80 may be a prognostic marker, but HR deficiency from low RAP80 doesn't predict platinum sensitivity.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- High-grade serous ovarian carcinoma (HGSOC) often exhibits impaired homologous recombination (HR) due to BRCA1/2 deficiencies, leading to platinum compound sensitivity.
- Other genetic alterations can also cause HR deficiency, impacting cancer progression and treatment response.
- RAP80 is an HR-pathway gene influencing BRCA1 activity, with potential implications for solid tumor outcomes.
Purpose of the Study:
- To investigate the prognostic significance of RAP80 gene expression in sporadic high-grade serous ovarian carcinoma (sHGSOC).
- To determine if RAP80 expression levels correlate with patient survival outcomes, including progression-free survival (PFS) and overall survival (OS).
Main Methods:
- Analyzed RAP80 mRNA expression in tumor samples from 35 sHGSOC patients treated with platinum-based chemotherapy.
- Utilized Cox regression analysis to assess the association between RAP80 expression and PFS/OS, adjusting for known prognostic factors (FIGO stage, residual disease, debulking surgery).
- Examined BRCA1 expression due to observed correlations with RAP80.
Main Results:
- Low RAP80 expression was significantly associated with shorter PFS (HR=1.449, p=0.007).
- Low RAP80 expression also correlated with shorter OS (HR=1.331, p=0.047).
- Median follow-up was 61.3 months, with median PFS of 20.2 months and median OS of 62.8 months.
Conclusions:
- RAP80 expression may serve as a novel prognostic biomarker in HGSOC patients.
- HR deficiency resulting from low RAP80 expression does not appear to confer hypersensitivity to platinum compounds in sHGSOC.
- Further research is warranted to elucidate the precise role of RAP80 in ovarian cancer biology and treatment.
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