Gene expression profile association with poor prognosis in epithelial ovarian cancer patients

Douglas V N P Oliveira,Kira P Prahm,Ib J Christensen,Estrid V Høgdall,Claus K Høgdall,Anker Hansen

doi:10.1038/s41598-021-84953-9

Douglas V N P Oliveira, Kira P Prahm + Show 4 more

Open Access

https://doi.org/10.1038/s41598-021-84953-9

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Abstract

Ovarian cancer (OC) is the eighth most common type of cancer for women worldwide. The current diagnostic and prognostic routine available for OC management either lack specificity or are very costly. Gene expression profiling has shown to be a very effective tool in exploring new molecular markers for patients with OC, although association of such markers with patient survival and clinical outcome is still elusive. Here, we performed gene expression profiling of different subtypes of OC to evaluate its association with patient overall survival (OS) and aggressive forms of the disease. By global mRNA microarray profiling in a total of 196 epithelial OC patients (161 serous, 15 endometrioid, 11 mucinous, and 9 clear cell carcinomas), we found four candidates—HSPA1A, CD99, RAB3A and POM121L9P, which associated with OS and poor clinicopathological features. The overexpression of all combined was correlated with shorter OS and progression-free survival (PFS). Furthermore, the combination of at least two markers were further associated with advanced grade, chemotherapy resistance, and progressive disease. These results indicate that a panel comprised of a few predictors that associates with a more aggressive form of OC may be clinically relevant, presenting a better performance than one marker alone.

Highlights

Ovarian cancer (OC) is the eighth most common type of cancer for women worldwide
Considering that 82% (161) of samples were derived from serous adenocarcinoma histologic subtype, we investigated whether our observations were due to this factor
In order to provide a better clinical significance, we investigated whether the combination of HSPA1A, CD99, RAB3A, and POM121L9P would be able to predict clinicopathological features mostly associated with poor patient prognosis

Summary

Introduction

Ovarian cancer (OC) is the eighth most common type of cancer for women worldwide. The current diagnostic and prognostic routine available for OC management either lack specificity or are very costly. We performed gene expression profiling of different subtypes of OC to evaluate its association with patient overall survival (OS) and aggressive forms of the disease. Full gene expression profiling has been employed in studies screening for potential molecular biomarkers capable to improve tumour classification and staging, predict chemotherapy response and impact on overall patient outcome[5,6,7]. We primarily investigated the association of gene expression profiles across different subtypes of EOC with overall survival (OS) of patients. Status Alive Death Median age in years (range) Median OS1 in months Median PFS in months (% progressed) Histology Serous adenocarcinoma Mucinous adenocarcinoma Endometrioid adenocarcinoma Clear Cell adenocarcinoma FIGO stage[2] I–II III–IV Histologic grade 1 2 3 Unknown Type I or II I II Risk group[3] Low High

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