HOXA1 is overexpressed in oral squamous cell carcinomas and its expression is correlated with poor prognosis

Abstract

BackgroundHOX genes encode homeodomain-containing transcription factors involved in the regulation of cellular proliferation and differentiation during embryogenesis. However, members of this family demonstrated oncogenic properties in some malignancies. The present study investigated whether genes of the HOXA cluster play a role in oral cancer.MethodsIn order to identify differentially expressed HOXA genes, duplex RT-PCR in oral samples from healthy mucosa and squamous cell carcinoma was used. The effects of HOXA1 on proliferation, apoptosis, adhesion, invasion, epithelial-mesenchymal transition (EMT) and anchorage-independent growth were assessed in cells with up- and down-regulation of HOXA1. Immunohistochemical analysis using a tissue microarray (TMA) containing 127 oral squamous cell carcinomas (OSCC) was performed to determine the prognostic role of HOXA1 expression.ResultsWe showed that transcripts of HOXA genes are more abundant in OSCC than in healthy oral mucosa. In particular, HOXA1, which has been described as one of the HOX members that plays an important role in tumorigenesis, was significantly more expressed in OSCCs compared to healthy oral mucosas. Further analysis demonstrated that overexpression of HOXA1 in HaCAT human epithelial cells promotes proliferation, whereas downregulation of HOXA1 in human OSCC cells (SCC9 cells) decreases it. Enforced HOXA1 expression in HaCAT cells was not capable of modulating other events related to tumorigenesis, including apoptosis, adhesion, invasion, EMT and anchorage-independent growth. A high number of HOXA1-positive cells was significantly associated with T stage, N stage, tumor differentiation and proliferative potential of the tumors, and was predictive of poor survival. In multivariate analysis, HOXA1 was an independent prognostic factor for OSCC patients (HR: 2.68; 95% CI: 1.59-2.97; p = 0.026).ConclusionOur findings indicate that HOXA1 may contribute to oral carcinogenesis by increasing tumor cell proliferation, and suggest that HOXA1 expression might be helpful as a prognostic marker for patients with OSCC.

Knowledge of Brazilian Dentists about Oral Cancer

“…Suggested that hypothesis based on fact that 10 to 20% of patients with oral cancer no related to use of tobacco and alcohol [11]. In literature, among oncogenic virus, Human Papilomavirus (HPV) is the most frequent in individuals with head and neck cancer [8,26,30]. In our study, no interviewed cited viruses infections as risk factor for oral cancer.…”

“…Oral cancer refers to all neoplasms that occur in oral cavity and lower lip [7][8][9]. Tobacco use is a major risk factor for the development of malignant lesions in the oral cavity.…”

“…Clinically, oral cancer presents as leukoplakic or erythroplastic blots or ulcerated lesions. In the early stages, is an asymptomatic lesion [5,8,13,[16][17][18]. The diagnosis of oral cancer is often performed late, and about 75 percent of cases are detected in advanced stages of the disease [3,19], causing a lower survival of 5-years in at least 50% of these patients [19].…”

Dynamic regulation of Nanog and stem cell-signaling pathways by Hoxa1 during early neuro-ectodermal differentiation of ES cells

“…Loss-of-function and lineage studies have implicated Hoxa1 in development of the inner ear, heart, neural crest specification, and hindbrain patterning (31)(32)(33). Growing evidence suggests roles for Hoxa1 in etiology of various cancers through modulation of cell proliferation, invasion, and metastasis (34)(35)(36)(37). These diverse functional roles for Hoxa1 appear to be at least partially related to its ability to influence key signaling pathways in differentiating cells (35).…”

Let-7c Inhibits NSCLC Cell Proliferation by Targeting HOXA1

“…Previous studies have suggested that HOXA1 is overexpressed in various cancers, including breast, liver, oral and lung cancer (Chariot et al, 1996;Abe et al, 2006;Bitu et al, 2012;Zha et al, 2012). The forced expression of HOXA1 promoted oncogenic transformation by modulating the p44/42 MAP kinase pathway and bcl-2 in MCF-10 cells (Mohankumar et al, 2007).…”