Aptamer-based analysis of plasma proteome of growing tumors

Background

In most cases, detecting malignancies at an early-stage increases treatment options, minimizes the risk of metastases and dramatically improves long-term survival. Nevertheless, tumors are typically discovered at more advanced stages, either with onset of symptoms or as part of unrelated procedures. Non-invasive means of detecting tumors in systemic circulation has long held considerable appeal, but also enormous challenges. A major difficulty is related to the need to detect a small volume of a malignancy remotely, after massive dilution of tumor-associated analytes in the total circulating volume of blood. To date, such “liquid biopsies” have mainly focused on the identification of genetic material unique to transformed cells, typically derived from circulating tumor cells, or cell-free DNA. With proteins, the presence of a tumor is more often accompanied with changes in the levels of endogenous, unmutated proteins in circulation. In this context, knowing which proteins represent the earliest markers or tumor presence would be enormously useful. So what are the first tumor-associated proteins that can be detected in blood as the initial transformed cells establish residence in their tissues of origin?

Methods

To answer this question, we used aptamer-based SomaScan® assay to monitor the time course of changes in the plasma proteome of mice carrying transplanted human tumors.

Results

Our study shows that tumor cells representing human lung, ovarian, breast and colon cancer produce both unique and common sentinel proteomic signatures in plasma that could be used to identify both the early presence as well as the identity of tumors growing remotely.

Conclusions

• Mouse models of human tumor growth reveal the emergence of early protein markers of tumor presence in plasma
• Unique and common markers exist for lung, colon, ovarian and breast cancer cell lines
• Tests based on multiple protein analytes reveal tumors at an early stage
• Protein-based tests can enhance the performance of liquid biopsies

Authors

Shashi Gupta¹
Matthew Westacott¹
Deborah G. Ayers¹
Daniel J. Schneider¹
Anis Karimpour-Fard²
Lawrence E. Hunter²
Daniel W. Drolet¹
Nebojsa Janjic¹

^1. SomaLogic Operating Co., Inc., Boulder, CO, USA
^2. University of Colorado School of Medicine, Aurora, CO, USA