Biomarker Associated With Longer Survival Uncovered in Ovarian Cancer

September 25, 2018

A new proteomic analysis found that CT45 is an independent prognostic factor in patients with high-grade serous ovarian cancer, and a potential target of immunotherapies.

A new proteomic analysis found that cancer/testis antigen 45 (CT45) is an independent prognostic factor in patients with high-grade serous ovarian cancer (HGSOC), and a potential target of immunotherapeutics. Patients with higher levels of CT45 had substantially better disease-free survival (DFS).

Standard treatment for HGSOC includes surgery and carboplatin/paclitaxel chemotherapy, and 80% of patients experience intra-abdominal recurrence requiring subsequent rounds of chemotherapy. “However, one in six patients remains disease free for more than 10 years after an initial diagnosis of advanced-stage metastatic disease,” wrote study authors led by Fabian Coscia, PhD, of the Max Planck Institute of Biochemistry in Martinsried, Germany. “At present, no known molecular mechanisms are associated with this prolonged survival, and no good predictor markers exist to distinguish these patients from others with HGSOC who do poorly.”

The investigators conducted a proteomic analysis of paraffin-embedded patient samples, including 11 HGSOC patients who were chemoresistant (median DFS, 190 days) and 14 patients who were chemosensitive (median DFS, 1,160 days). The results of this analysis were published in Cell.

From an overall collection of more than 9,000 proteins, the researchers identified CT45 as a significant variable between the groups. Patients with high CT45 expression (top quartile) had a median DFS of 2,754 days, compared with a median of 366 days for all other patients (P = .008). Overall survival was also significantly better, at 2,903 days compared with 1,078 days (P = .016).

They confirmed the finding in a separate set of more than 200 cases of primary and metastatic epithelial ovarian cancer. In that cohort, CT45 expression was correlated with chemosensitivity in 124 patients with advanced-stage disease (P = .005). In 42 patients with high CT45 expression, DFS was prolonged compared with those with no expression (363 days vs 153.5 days; P = .02). One further cohort of 284 HGSOC patients from the Cancer Genome Atlas again confirmed the finding.

The investigators found that CT45 is connected to DNA damage pathways via interaction with the PP4 phosphatase complex. “We suspect that CT45 plays a major role in the response of tumors to carboplatin,” said Marion Curtis, PhD, a co-author at the University of Chicago, in a press release. “This gives us hope that future strategies that activate CT45 expression in the tumor could make it more sensitive to carboplatin treatment.”

The authors wrote that there could be significant clinical implications to these findings, given the apparent connection between CT45 and long-term survival. “A treatment strategy in which CT45 expression is reactivated using demethylating agents, which are in clinical trials, may be effective against tumors lacking CT45,” they wrote. “Based on our results, expression of CT45 is expected to improve the efficacy of platinum-based chemotherapy or immunotherapy for patients with advanced-stage ovarian cancer.”