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.
Highlights
Lung cancer is the leading cause of cancer-related deaths worldwide, and in the United States an estimated 221,200 new cases were expected to be diagnosed in 2015 [1]
To study whether receptor for hyaluronic acid-mediated motility (RHAMM) expression correlates with proliferation of primary lung adenocarcinomas, we stained a subset of lung adenocarcinomas (n = 12) with a proliferation marker, Ki67
We found no significant correlation between RHAMM expression and proliferation as measured by Ki67 (p = 0.335, Figure 1B)
Summary
Lung cancer is the leading cause of cancer-related deaths worldwide, and in the United States an estimated 221,200 new cases were expected to be diagnosed in 2015 [1]. Despite the improvements in diagnosis and therapy made during the past few years, the overall survival of lung cancer patients remains poor because the majority (57%) are diagnosed after the cancer has metastasized. Some Food and Drug Administration (FDA) approved drugs for stage IV lung adenocarcinoma target molecular alterations including mutations in epidermal growth factor receptor (EGFR) and rearrangements of anaplastic lymphoma kinase (ALK) [4]. These molecular alterations are present in only 20% of patients with lung adenocarcinoma. There is a critical need to develop predictive biomarkers of the metastatic potential of NSCLC, to prevent metastases from developing, and to treat metastatic lung cancer
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