Plasma protein biomarker discovery for ovarian cancer

Ovarian cancer (OvCa) is the fifth deadliest cancer in females with over 300,000 new cases and over 200,000 deaths per year. OvCa has an overall 5-year survival of only 30-50%. Survival increases to over 90% when detected in stage I, but is only 20% when detected in stage IV. Thus, there is a pressing clinical need for accurate biomarkers that enable the early detection of OvCa.

This study measured plasma protein levels in two independent cohorts with women surgically diagnosed with benign or malign conditions after suspicion of OvCa. In total, plasma protein levels of 404 women were measured using the Olink® Explore HT (5400+ unique proteins) platform and its predecessor, Olink® Explore 3072 (~3000 unique proteins). Technical comparisons of 2,844 assays overlapping between the two platforms revealed a strong median R correlation of 0.91, demonstrating that Olink Explore HT delivers the same high data quality as Olink Explore 3072, even with its expanded proteome coverage.

Using one of the investigated cohorts as discovery, we searched for biomarkers that were indicative of early (stage I-II), late (stage III-IV), or any stage cancer compared to benign tumors, and after strict adjustment for multiple hypothesis testing, we found a total of 327 such associations. These associations corresponded to 191 unique proteins, including early-stage cancers compared to benign and with both increased or decreased circulating levels in malign cases compared to benign. Using the second cohort as validation, 99.7% (326) of these associations were then replicated. All of the biomarker candidates were found to have similar fold change (Pearson"s R=0.93, p < 3.0 x 10-140) between the two cohorts. Thirty-six of the 191 proteins (19%) were unique to the Olink Explore HT platform. MUCIN-16 (CA-125), a well-known OvCa marker used in the clinic, was not found to be significantly different between early-stage cancers and benign tumors and was not among the top 5 ranked biomarker candidates.

This study highlights the potential of Olink Explore HT to enhance the discovery of biomarkers for early-stage OvCa detection, deepen our understanding of disease biology, and open new avenues for potential therapeutics.