Expression of the receptor for hyaluronic acid mediated motility (RHAMM) is associated with poor prognosis and metastasis in non-small cell lung carcinoma
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Dunrui Wang1,*, Navneet Narula2,*, Stephanie Azzopardi2, Roger S. Smith3, Abu Nasar4, Nasser K. Altorki4, Vivek Mittal4, Romel Somwar3, Brendon M. Stiles4, Yi-Chieh Nancy Du2
1Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
2Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, USA
3Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
4Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, NY 10065, USA
*These authors contributed equally to this work
Yi-Chieh Nancy Du, email: firstname.lastname@example.org
Keywords: lung cancer, receptor for hyaluronic acid-mediated motility, metastasis, prognosis
Received: November 17, 2015 Accepted: May 09, 2016 Published: May 23, 2016
The receptor for hyaluronic acid-mediated motility (RHAMM) is upregulated in various cancers, but its role in primary and metastatic non-small cell lung carcinoma (NSCLC) remains to be determined. Here, we investigate the clinical relevance of RHAMM expression in NSCLC. RHAMM protein expression correlates with histological differentiation stages and extent of the primary tumor (T stages) in 156 patients with primary NSCLC. Importantly, while focal RHAMM staining pattern is present in 57% of primary NSCLC, intense RHAMM protein expression is present in 96% of metastatic NSCLC cases. In a publicly available database, The Cancer Genome Atlas (TCGA), RHAMM mRNA expression is 12- and 10-fold higher in lung adenocarcinoma and squamous lung carcinoma than in matched normal lung tissues, respectively. RHAMM mRNA expression correlates with stages of differentiation and inferior survival in more than 400 cases of lung adenocarcinoma in the Director’s Challenge cohort. Of 4 RHAMM splice variants, RHAMMv3 (also known as RHAMMB) is the dominant variant in NSCLC. Moreover, shRNA-mediated knockdown of RHAMM reduced the migratory ability of two lung adenocarcinoma cell lines, H1975 and H3255. Taken together, RHAMM, most likely RHAMMv3 (RHAMMB), can serve as a prognostic factor for lung adenocarcinomas and a potential therapeutic target in NSCLC to inhibit tumor migration.
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