(HealthDay News) — Elevated salivary levels of CD44 and total protein (TP) can identify head and neck cancer patients with an increased risk for cancer recurrence, according to a study published online Aug. 15 in JAMA Otolaryngology-Head and Neck Surgery.
Elizabeth J. Franzmann, M.D., from the University of Miami Health System and Jackson Memorial Hospital, and colleagues conducted a multi-institutional nonrandomized clinical trial testing a novel diagnostic/screening assay to examine whether soluble CD44 and TP are useful for monitoring head and neck cancer recurrence in a point-of-care (POC) test. Oral rinses were collected at pretreatment baseline and at three, six, 12, and 18 months after completion of therapy. To define disease status, participants were followed for three years.
Among the 172 patients who were enrolled, the researchers found an association for tumor site with test results at baseline; a higher baseline positive POC test rate was seen for patients with oral cavity cancer versus oropharyngeal cancer (92.2 versus 77.3 percent). A higher CD44 level showed a significant association with a higher risk for recurrence using Cox regression models with CD44 or TP level as a time-varying covariate (hazard ratio, 1.06). Higher CD44 and TP levels were associated with increased hazard ratios of recurrence of 1.13 and 3.51, respectively, in a multivariate adjusted analysis.
“Our study suggests biomarker detection in saliva collected from an oral rinse after initial treatment offers potential to readily assess recurrence risk,” Franzmann said in a statement. “Elevated levels of either of two biomarkers were associated with disease return.”
One author disclosed ties to the biopharmaceutical industry and is the inventor of the intellectual property used in the study.
What is CD44?
CD44, a type I transmembrane glycoprotein, plays a crucial role in various cellular functions, including adhesion, migration, and signaling. It is abundantly expressed on the surface of most normal and tumor cells. In the context of cancer, CD44 has been extensively studied due to its involvement in tumor progression, metastasis, and chemoresistance.
One of the key functions of CD44 in cancer is its ability to mediate cell adhesion and migration. CD44 interacts with extracellular matrix (ECM) components, such as hyaluronic acid, facilitating cell attachment and migration. This interaction is essential for tumor invasion and metastasis, as cancer cells must detach from the primary tumor, migrate through the ECM, and colonize distant organs. Overexpression of CD44 has been correlated with increased tumor invasiveness and metastasis in various cancer types.
In addition to its role in cell adhesion and migration, CD44 also functions as a signaling molecule. CD44 can interact with various signaling pathways, including the MAPK, PI3K-AKT, and NF-κB pathways, which are involved in cell proliferation, survival, and invasion. Activation of these pathways by CD44 can promote tumor growth and progression. Moreover, CD44 has been implicated in the development of chemoresistance, as it can activate signaling pathways that confer resistance to chemotherapy drugs.
CD44 exists in various isoforms generated by alternative splicing. These isoforms differ in their expression patterns and functional properties. For example, the standard form (CD44s) is expressed on most cell types, while variant isoforms (CD44v) are preferentially expressed in certain cell types, including cancer cells. Specific CD44 isoforms have been associated with different stages of tumor progression and metastasis.
Targeting CD44 has emerged as a promising therapeutic strategy for cancer treatment. Several approaches are being investigated, including the use of antibodies that block CD44-mediated interactions, small molecule inhibitors that target CD44 signaling pathways, and vaccines that induce an immune response against CD44. However, further research is needed to fully understand the complex role of CD44 in cancer and to develop effective therapeutic interventions.
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