BMC Cancer 2009, 9:11 http://www.biomedcentral.com/1471-2407/9/11 1.0 0.9 0.8 ig0.7 n ivvg0.6 r su0.5 iton0.4 rpo0.3 o rP0.2 0.1 0.0 1.0 0.9 0.8 g0.7 ivn0.6 i v rsu0.5 ino0.4 t rop0.3 roP0.2 0.1 0.0 0 A 0 C 10 20 30 Follow-up time (months) p= 0.003 40 50 10 20 30 Follow-up time (months) p=0.049 40 50 1.0 0.9 0.8 ing 0.7 ivv 0.6 r su 0.5 n ito 0.4 rpo 0.3 o rP 0.2 0.1 0.0 p= 0.002 0 10 20 30 Follow-up time (months) 40 50 B GLUT3 (+) GLUT3 (-) N= 49 FKiagpularne-M3eier plot showing over-all survival Kaplan-Meier plot showing over-all survival. A; relapse-free survival. B; and disease-free survival. C in patients demon- strating GLUT3 over-expression. Malignant cells show an increased glucose uptake in vitro and in vivo [21,22]. This process is thought to be medi- ated by glucose transporters (GLUTs), the expression and activity of which is regulated by oncogenes, growth factors and cytokines [23,24]. Studies of GLUT genes in human cancers have shown over-expression of GLUT1 and GLUT3 in cancers of various sites including the head and neck [25-28]. Recent studies in laryngeal carcinoma dem- onstrated an association between GLUT3 protein levels and poorer outcome [29]. HSAL2 is a member of a gene family that encodes a group of putative transcription fac- tors. Evidence from various studies suggests that the HSAL gene family is necessary for normal embryonic develop- ment and genetic alterations can lead to human congeni- tal defects and cancer [30,31]. HSAL2 is thought to have a role as a tumor suppressor gene in ovarian cancer [32]. The present study suggests the potential role of GLUT3 and HSAL2 in oral tongue SCC. Proprotein convertases (PC) are a family of serine endoproteases that play impor- tant roles in regulating cell function by converting propro- teins to biologically active molecules such as neuropeptides and polypeptide hormones, protein tyro- sine phosphatases, growth factors and their receptors, and enzymes including MMPs. Numerous members of the PC family have been associated with invasion and prolifera- tion in various cancers including head and neck, breast and lung cancers [33-35]. PCs are thought to activate cer- tain substrates that may play a significant role in carcino- genesis. Among these substrates are MMPs which are known to be involved in the degradation of extracellular matrix, a key process in the initiation of tumor microinva- sion into the connective tissue. PACE4, a member of the PC family, activates membrane type MMPs (MT-MMPs). Bassi et al. demonstrated that PACE4 expression results in enhanced susceptibility to carcinogenesis in vivo [35]. In the present study, PACE4 failed to show clinical signifi- cance when validated by real-time RT-PCR likely due to the small sample size and heterogeneous nature of the specimens. There is growing literature on the use of microarray tech- nology to examine genomewide genetic expression changes associated with head and neck SCC development and to identify biomarkers as it relates to response to ther- apy and clinical outcome [5-10]. However, there is dis- cordance among the studies. Furthermore, the biomarkers Page 9 of 13 (page number not for citation purposes)