Scientists have identified a blood protein biomarker that can help diagnose early-stage lung cancer without the need for invasive procedures, and could potentially represent a therapeutic target. The protein is a stable variant of the nuclear matrix-associated DNA replication factor Ciz1, which in its native form plays a key role in DNA replication. A team at the U.K.’s University of York has now found that a truncated version of the protein is expressed by lung tumor cells, but not normal lung tissue surrounding the tumor, and can be detected in the blood. The discovery has led to the founding of University of York spinout Cizzle Biotech, which aims to exploit the Ciz1 IP for diagnostic and potentially therapeutic applications.
The reported studies by Dawn Coverley, Ph.D., and colleagues, showed that presence of the Ciz1 variant in blood plasma could accurately identify patients with stage 1 lung cancer. Blood tests on two separate cohorts of patients confirmed that Ciz1 levels above a specific threshold correctly classified 95–98% of small cell lung cancers (SCLC) and non-SCLC patients, with a specificity of 71–75%. Their calculations indicated that if the test were applied as a secondary screen to high-risk individuals with suspicious CT results it could halve the number of individuals who need to be referred for invasive follow-up procedures.
Encouragingly, using a short-hairpin RNA to knock down production of the Ciz1 variant, either in vitro or in a xenograft model of SCLC, led to a dramatic reduction in tumor growth, which the York team says identifies the protein as a functionally relevant driver of tumor cell proliferation. The researchers report their findings in PNAS, in a paper titled “Variant Ciz1 is a circulating biomarker for early-stage lung cancer.”
“By looking for variant Ciz1 in the blood we can pick out people who have small tumors in their lungs, without the need to take a biopsy or undergo surgery,” Dr. Coverley states. “We think that the test will be especially powerful when combined with X-ray or CT imaging, and will offer doctors an alternative way to test whether an abnormal growth is cancerous. For the patient, this means that many could avoid invasive diagnostic procedures altogether.”