Authors: | Wang, D.; Narula, N.; Azzopardi, S.; Smith, R. S.; Nasar, A.; Altorki, N. K.; Mittal, V.; Somwar, R.; Stiles, B. M.; Du, Y. C. N. |
Article Title: | Expression of the receptor for hyaluronic acid mediated motility (RHAMM) is associated with poor prognosis and metastasis in non-small cell lung carcinoma |
Abstract: | 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. |
Keywords: | immunohistochemistry; adult; cancer survival; controlled study; human tissue; protein expression; aged; unclassified drug; human cell; major clinical study; histopathology; drug targeting; cancer staging; protein analysis; gene; metastasis; gene expression; tumor differentiation; cohort analysis; genetic variability; lung cancer; cancer genetics; lung adenocarcinoma; messenger rna; alternative rna splicing; gene silencing; tissue microarray; short hairpin rna; migration inhibition; non small cell lung cancer; cancer prognosis; prognosis; human; male; female; article; lung cancer cell line; squamous cell lung carcinoma; receptor for hyaluronic acid-mediated motility; hyaluronic acid binding protein; receptor for hyaluronic acid mediated motility protein; h1975 cell line; h3255 cell line; rhammv3 gene |
Journal Title: | Oncotarget |
Volume: | 7 |
Issue: | 26 |
ISSN: | 1949-2553 |
Publisher: | Impact Journals |
Date Published: | 2016-06-28 |
Start Page: | 39957 |
End Page: | 39969 |
Language: | English |
PROVIDER: | scopus |
PUBMED: | 27220886 |
DOI: | 10.18632/oncotarget.9554 |
PMCID: | PMC5129984 |
DOI/URL: | |
Notes: | Article -- Export Date: 1 September 2016 -- Source: Scopus |