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. 2024 Nov 19;14(1):28573.
doi: 10.1038/s41598-024-80030-z.

Decoding the pathological and genomic profile of epithelial ovarian cancer

Rim Rejaibi  1   2   3   4 , Arnaud Guille  3 , Maroua Manai  3   5 , Jose Adelaide  3 , Emilie Agavnian  4 , Aida Jelassi  1   2 , Raoudha Doghri  1   6 , Emmanuelle Charafe-Jauffret  4   7 , François Bertucci  3   8 , Mohamed Manai  2 , Karima Mrad  1   6 , Lamia Charfi  1   6 , Renaud Sabatier  9   10
Affiliations

Decoding the pathological and genomic profile of epithelial ovarian cancer

Rim Rejaibi et al. Sci Rep. .

Abstract

Ovarian cancer (OC) is one of the most common cancers in women, with a high mortality rate. Most of published studies have been focused on Caucasian populations, with the need to explore biological features and clinical outcomes of patients from other ethnicities. We described clinical outcome (progression-free survival and overall survival) and biomarkers associated with survival in a cohort of patients with OC from Tunisia. Using immunohistochemistry, we assessed the expression of 14 proteins known to be altered in OC in a cohort of 198 patients. We explored the correlation between protein expression and copy number alteration (CNA) profiles. FIGO stage, menopausal status and mismatch repair deficiency were associated with survival. ERBB2 amplification was correlated with high ERBB2 expression (OR = 69.32, p = 4.03 E-09), and high PDL1 expression was associated to CD274 amplification (OR = 4.97, p = 5.79 E-2). We identified a correlation between survival and exposure to two CNA signatures (MAPK pathway and BRCA-related homologous recombination deficiency). Moreover, Gama-H2AX protein expression was correlated with exposure to a genomic signature associated with homologous recombination deficiency. We observed that OC clinical and pathological characteristics of these patients from Tunisia were similar to those of Caucasian patients. We identified frequent CNA in this population that need to be confirmed in other sets from Africa.

Keywords: Copy number alterations; Ovarian cancer; Survival.; Tissue micro-array.

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Conflict of interest statement

Declarations Competing interests The authors declare no competing interests. Approval for human experiments Specimens for the EOC-TMA were gathered from the SAI. All patients willingly provided specimens, accompanied by written informed consent, and the study received approval from the Institutional Ethics Committee at SAI (Number 2150, September 2020). The methods employed adhered to pertinent guidelines and regulations. Our study adhered to the Code of Ethics of the World Medical Association (Declaration of Helsinki), as published in the British Medical Journal on July 18th, 1964. Ethics declarations Specimens for the EOC-TMA were gathered from the SAI. All patients willingly provided specimens, accompanied by written informed consent, and the study received approval from the Institutional Ethics Committee at SAI (Number 2150, September 2020). The methods employed adhered to pertinent guidelines and regulations. Our study adhered to the Code of Ethics of the World Medical Association (Declaration of Helsinki), as published in the British Medical Journal on July 18th, 1964. Informed consent was obtained from all subjects involved in the study.

Figures

Fig. 1
Fig. 1
Kaplan-Meier curve for progression-free survival (A) and overall survival (B).
Fig. 2
Fig. 2
Copy number alterations profiles of EOC tumors. Frequency plot of recurrent copy number alterations was identified in OC tumors using the GISTIC algorithm. Frequencies of gains (left) and losses (right) are plotted due to chromosome location. X-axis: top = log–scale ratio; bottom = q-values. Left hand-side panel represent CNV analysis in high-grade serous tumor. Right hand-side panel represents CNV analysis in samples of other pathological subtypes.
Fig. 3
Fig. 3
Association of survival with copy-number signatures. Upper panel: Stacked barplots show CNA signatures exposures for each patient. Patients were ranked by risk of death estimated by a multivariate Cox proportional hazards model stratified by age and cohort, with CNA signature exposures as covariates. Lower panel: Linear fit of signature exposures ordered by risk predicted by the Cox proportional hazards model.
Fig. 4
Fig. 4
Association between IHC expression and CNA signatures (only statistically significant correlations are shown here, full data are available in Supp Figure S4). Dots color represents the pathological subtype of each tumor: light blue = serous, dark blue = clear cell, red = mucinous, orange = endometrioid, grey = mixed.
See this image and copyright information in PMC

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