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Microscopic view of parotid cancer tissue biopsy.
The positive data from the lab-based approach aided the development of a point-of-care device that measures the protein ratio and could be used directly in a clinic.

Changes in Protein Levels Help Diagnose Oral Cancer

Per the NIH, head and neck cancer makes up about 5 percent of all cancers worldwide and 3 percent of all malignancies in the US

Case Western Reserve University
Published:Mar 04, 2024
|2 min read
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CLEVELAND, OH — Oral cancers and precancerous mouth lesions are considered especially difficult to diagnose early and accurately. For one, biopsies are expensive, invasive, stressful for the patient, and can lead to complications. They’re also not feasible if repeated screenings of the same lesion are required.

A team of researchers at the Case Western Reserve University (CWRU) School of Dental Medicine has discovered a noninvasive, low-cost test to detect oral cancer, monitor precancerous lesions, and determine when a biopsy is warranted.

Their findings, published recently in Cell Reports Medicine, are based on a scoring system linked to the levels of two proteins in cells brushed from suspicious oral lesions of patients at dental clinics or the ear, nose, and throat department at University Hospitals (UH).

Changes in protein expression in various cancer stages

One of the proteins (human beta-defensin 3 or hBD-3) is expressed at high levels in early-stage oral cancer, while the second (hBD-2) is low or unchanged. The ratio of hBD-3 to hBD-2 in the lesion site—over the ratio of the two proteins on the opposite, normal site—generates a score, called the beta-defensin index (BDI).

A score above a predetermined threshold implies cancer; anything below does not. Determining the levels of the proteins and quantifying the BDI is done routinely in a lab. The BDI was independently validated using identical protocols at CWRU/UH, University of Cincinnati Medical Center, and West Virginia University School of Dentistry.

“When we first discovered hBD-3, we saw it acted as a ‘good guy,’ involved in wound-healing and killing microbes," said Aaron Weinberg, PhD, DMD, chair of the Department of Biological Sciences at the CWR School of Dental Medicine and the study’s lead researcher. “When we found it was regulated the same way certain cells grow uncontrollably, we started studying hBD-3 in the context of oral cancer.

“We found it was not only promoting tumor growth but was overexpressed in the early stages of the disease, while another member, hBD-2, wasn’t changing. This difference in levels of expression of the two proteins compared to the opposite side in the same patient led us to examine the BDI’s ability to distinguish cancer from benign lesions.”

Impact of the BDI testing approach

Head and neck cancer (HNC), of which oral cancer is about 90 percent, is the seventh-most prevalent malignancy in the world, and developing countries are witnessing a rise in its incidence. There are about 640,000 cases of HNC per year, resulting in about 350,000 deaths worldwide, mainly in socioeconomically disadvantaged populations and underserved communities.

The study’s lab-based approach, which is now patented, can reduce biopsies in primary care clinics by 95 percent because it can tell clinicians who actually needs a biopsy, said Weinberg. The test can also be used in developing countries where oral cancer is rampant and pathology services are questionable or lacking, he said.

The positive data from the lab-based approach has inspired the development of a point-of-care (POC) device in collaboration with Umut Gurkan, PhD, the Wilbert J. Austin Professor of Engineering at the Case School of Engineering. The POC diagnostic approach measures the protein ratio and could be used directly in a clinic, providing results within half an hour.

Working through CWR’s Technology Transfer Office, a patent for the device is pending, setting up possible manufacturing and clinical validation as the next step.

- This press release was originally published on the Case Western Reserve University website