Gene Expression Profiles Show Promise for Prognosis in Ovarian Carcinoma

November 22, 2019

Researchers compared primary high grade serous ovarian carcinoma tumors and their matched metastasis, showing evidence of separating the 2 sample types and potentially predicting patient survival.

A study published by BMC Cancer identified functional categories of genes and transcription factors that could play important roles in promoting metastases and serve as markers for cancer prognosis.1

By comparing the gene expression profiles of primary high grade serous ovarian carcinoma (HGSOC) tumors and their matched metastasis, researchers provided evidence that a signature of 100 genes can separate these 2 sample types and potentially predict patient survival.

“These findings serve candidates for future research and could lead to improved treatments for HGSOC in the future,” the researchers wrote.

In this comparative transcriptome analysis, the gene expression profile of 10 primary tumors and 10 related metastases were analyzed using RNA sequencing. The differentially expressed genes were associated with decreased embryogenesis and vasculogenesis and increased cellular proliferation and organismal death. Top upstream regulators responsible for this gene signature were NR5A1, GATA4, FOXL2, TP53, and BMP7.

A subset of these genes was highly expressed in the ovarian cancer among the cancer transcriptomes of The Cancer Genome Atlas. Additionally, the metastatic gene signature was suggestive of poor survival in TCGA data based on gene enrichment analysis.

“Deciphering the molecular mechanisms and similarities of metastatic transformation and recurrence of primary tumors will be important for understanding the pathogenesis of the disease and to improve the treatment, especially in advance stage,” the researchers wrote.

Several recent studies have identified molecular subtypes of ovarian cancer by gene expression profiling which aims to link expression to clinical and pathologic features. Researchers referenced the 2008 study carried out by Tothill et al., in which the authors clustered and divided the HGSOC gene expression data into 4 subgroups, later on confirmed in the TCGA study and termed mesenchymal (C1), immunoreactive (C2), differentiated (C4), and proliferative (C5).

Results within this study suggested that the upregulated genes of the cluster C1 were able to separate the primary tumor signature from omental signature much better than any other subgroup genes. However, this suggests that the mesenchymal C1 gene signature was more prominent in the omental samples compared to the primary tumors.

“Overall, our analysis reveals novel aspects of metastatic transformation of HGSOC, with potentially important implications for prognosis and therapy,” the researchers wrote.

Ovarian cancer is the 7th most common cancer in females worldwide, with a rate of 6 per 100,000. By the time of diagnosis, almost 70% of patients with ovarian cancer have widely disseminated disease with intraperitoneal carcinosis and ascites.

HGSOC accounts for more than 60% of epithelial ovarian cancers and over 70% of all ovarian cancer deaths, according to a 2018 article in Cancers. Therefore, not only is HGSOC the most common ovarian cancer, but also the deadliest.2

References:
1. Sallinen H, Janhonen S, Pölönen P et al. Comparative transcriptome analysis of matched primary and distant metastatic ovarian carcinoma. BMC Cancer 19, 1121 (2019). doi:10.1186/s12885-019-6339-0.
2. Jaeyeon K, Park EY, Kim O, Schilder JM, Coffey DM, Cho CH, Bast RC Jr. Cell Origins of High-Grade Serous Ovarian Cancer. Cancers. doi:10.3390/cancers10110433.