Hence the present study intended to investigate whether DNA

Hence, the present study intended to investigate whether DNA promoter hypermethylation can further amplify the stratifying effectiveness in this clinically debating patient population. Four candidate iepd were selected for validation, of which we mainly focused on RASSF1A and DAPK due to their potential role in predicting clinical outcomes in oral cancers.[27], [29]
Materials and methods
Results
Discussion
Study limitations The present study has several limitations. First, this study was conducted retrospectively; thus, selection bias inevitably exists and cannot be adequately adjusted even after multivariate analysis. Second, a relatively small sample size is noted despite the pros of the unique study population. Third, as mentioned above, it is not available to perform a match-paired analysis by using an internal-control group that contained patients with unexpected close margin of⩽5 mm but not treated with post-operative RT. Therefore, interpreting our data should be cautioned; other large and prospective studies should be conducted to confirm the results.
Conclusions In buccal cancer patients who were radically resected but encountered an unexpected close pathological margin, combined very close margin and DAPK promoter hypermethylation predict poor post-irradiation clinical outcomes. Thus, for these patients, more aggressive management should be considered, such as re-dissection to gain a wider margin or a combination of chemotherapy, RT, and de-methylating therapies, rather than post-operative observation or RT alone.
Conflict of interest statement
Role of the funding source
Acknowledgments
Introduction Death-associated protein kinase (DAPK; also known as DAPK1) is a calmodulin (CaM)-regulated serine/threonine kinase and possesses multiple structural and functional domains, including a kinase domain, a CaM binding motif, eight ankyrin repeats (ARs), a cytoskeleton binding region, and a death domain (Deiss et al., 1995). Several lines of evidence indicate a role of DAPK in tumor suppression. DAPK expression is frequently reduced in various human tumor cell lines and tissues, and this DAPK downregulation correlates with the recurrence, metastatic progression, or unfavorable prognosis of several human cancers (Raveh and Kimchi, 2001, Bialik and Kimchi, 2004). Furthermore, DAPK is capable of suppressing oncogenic transformation in vitro (Raveh et al., 2001) and blocking tumor metastasis in vivo (Inbal et al., 1997). DAPK was identified based on its death-promoting effect (Deiss et al., 1995) and has been subsequently found to mediate apoptotic and autophagic death induced by a wide spectrum of stimuli (Cohen et al., 1997, Cohen et al., 1999, Inbal et al., 1997, Inbal et al., 2002, Raveh et al., 2001, Jang et al., 2002, Pelled et al., 2002). The proapoptotic function of DAPK is attributed in part to its effect on integrin inactivation, thereby suppressing adhesion-mediated survival signal (Wang et al., 2002). In addition to promoting cell death, DAPK elicits cytoskeleton remodeling effect through phosphorylating myosin light chain 2 (MLC) (Kuo et al., 2003, Bialik et al., 2004). Furthermore, DAPK functions as a potent inhibitor of cell migration (Kuo et al., 2006). It is believed that the proapoptotic and antimigratory activities of DAPK could act as a double safeguard mechanism to prevent malignancy.