Modelling metastasis

A protein-based metastasis risk prediction tool could reduce unnecessary colon cancer surgeries.

Simplified graphical illustration depciting the anatomy of the human body. Image credit: (CC0)

Most patients with early-stage colorectal cancer can be treated with a minimally invasive procedure. Surgeons use a flexible tool to remove precancerous or cancerous cells, cutting the risk of death from colorectal cancer in half. But a small number of early-stage colorectal cancer patients are at risk of their cancer spreading to the lymph nodes. These patients need more extensive surgery. Clinicians use risk stratification tools to decide which patients need more extensive surgery.

Unfortunately, the existing risk stratification tools are not very accurate. The current approach, which analyzes colon tissue for cancerous changes, classifies 70% to 80% of early-stage colorectal cancer patients as high risk for cancer spread. But only about 8% to 16% of patients in the high risk group have lymph node metastasis. As a result, many patients undergo unnecessary, invasive surgery.

Zhuang, Zhuang, Chen, Qin, et al. developed a more accurate way to predict which patients are at risk of lymph node metastasis using proteins. In the experiments, the team analyzed the proteins in tumor samples from 143 patients with early colorectal cancer who did not have lymph node metastases and 78 patients with metastases. Zhuang et al. then used machine learning to build a prediction tool that used 55 proteins to identify patients at risk of metastases. The new approach was more accurate than existing tools and simplified versions with only nine or five proteins also performed better than existing tools.

This work provides preliminary evidence that protein-based models using as few as five proteins can more accurately identify which patients are at risk of metastasis. These models may reduce the number of patients who undergo unnecessary invasive surgery. The experiments also identified potential targets for therapies to prevent or treat lymph metastases. For example, they showed that low levels of the RHOT2 protein predict metastasis.