Low Levels of 1-Asparaginase Predict Cancer Recurrence

Loss of expression of the enzyme ASRGL1 (l-asparaginase) was shown to be an independent biomarker for disease-specific survival in uterine cancer (endometrioid endometrial carcinoma).

Endometrial cancer of the uterus is the most common form of gynecologic cancer in Europe and North America. The treatment primarily consists of removing the uterus with follow-up chemotherapy in cases where the risk of recurrence is deemed high. Investigators at Uppsala University, the University of Turku, and the University of Bergen searched for a biomarker to facilitate determination of risk of the disease reoccurring.

The investigators used The Human Protein Atlas, to identify l-asparaginase (ASRGL1) as an endometrial carcinoma biomarker candidate. They then used a microarray immunohistochemical technique to evaluate ASRGL1 expression in samples collected from 500 women who had been diagnosed with uterine cancer between the years 1981 and 2007.

Results revealed that the ASRGL1 enzyme was highly expressed in normal endometrium and heterogeneously expressed in endometrial carcinoma. Patients with little or no ASRGL1 expression in their tumor cells were found to have a much higher risk of cancer recurrence or death, while patients with sustained high levels of ASRGL1 had a much lower risk of recurrence. ASRGL1 was found to be an independent prognostic factor, even after compensating for other risk factors such as tumor stage and tumor grade.

"I view the results as a first step towards personal treatment of uterine cancer. Today, 10-15% of the patients suffer recurrences, even though they were considered low risk patients according to classic diagnostics. By using ASRGL1, the chance of identifying such hidden high-risk patients and offer them more aggressive treatment after their operation increases," said first author Dr. Per-Henrik Edqvist, associate professor of immunology, genetics, and pathology at Uppsala University. "The Protein Atlas project enabled our discovery, and our study is an excellent example of how The Human Protein Atlas database can be used by researchers across the world to find interesting leads to follow up on."

The work was published in the April 6, 2017, online edition of the journal Gynecologic Oncology.