Oncology Medical News about Nectin-4 Oncoprotein, lung cancer

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Identification of Nectin-4 oncoprotein as a diagnostic and therapeutic target for lung cancer
Cancer Research, 08/18/09

Takano A et al. - In a study to assess the activity of Nectin-4 oncoprotein in lung cancer, it was shown that Nectin-4 might play a significant role in lung carcinogenesis, and it should be a new candidate serum and tissue biomarker, as well as a therapeutic target.

Methods

Gene expression profile analysis of lung cancers revealed the transactivation of an immunoglobulin-like molecule Nectin-4 in the majority of non–small cell lung cancers (NSCLC).
Immunohistochemical staining of 422 NSCLCs showed that a high level of Nectin-4 expression was associated with poor prognosis for NSCLC pts, and multivariate analysis confirmed its independent prognostic value.

Results

We established an ELISA to measure serum Nectin-4 and found that serum Nectin-4 levels were significantly higher in NSCLC pts than in healthy volunteers.
The proportion of the serum Nectin-4–positive cases was 88 of 164 (53.7%) NSCLCs, whereas only 3 of 131 (2.3%) healthy volunteers were falsely diagnosed as positive, which was superior to carcinoembryonic antigen (CEA) and cytokeratin 19-fragment (CYFRA21-1) in sensitivity and specificity.
A combined ELISA for both Nectin-4 and CEA increased sensitivity and classified 65.0% of lung adenocarcinomas as positive with false-positive rate of 4.6%.
Use of both Nectin-4 and CYFRA21-1 classified 68.3% of lung squamous cell carcinomas as positive with false-positive rate of 6.1%.
Treatment of lung cancer cells with small interfering RNAs against Nectin-4 suppressed its expression and cell growth.
Exogenous expression of Nectin-4 increased the lamellipodia formation and the invasive ability of mammalian cells through activation of small GTPase Rac1.

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