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

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.

Figure 1

Analysis workflow.

Figure 2

Overall survival and prediction performance of the 4 candidates. (a) Survival curve shows that “high risk” (all candidates overexpressed) group has a shorter survival compared to “low risk” (at least one candidate down regulated) OC patients. (b) AUC/ROC curve of combination of HSPA1A, CD99, RAB3A and POM121L9P for 5-year OS. P value and AUC are presented above.

Figure 3

Progression-free survival for patients with overexpressed mRNA candidates. Survival curve shows that “high risk” (all overexpressed candidates) group have an overall shorter time to recurrence outcome compared to “low risk” (at least one candidate downregulated) in OC patients. P value is presented above.