relation in between pATM expression and 10-year general (left panels) and disease-specific (correct panels) survival of melanoma sufferers classified as negative (Neg), weak-to-moderate (Weak-Mod) & strong (A and B), and as negative-to-moderate (Neg-Mod) & strong (C and D).
Next we tested the prognostic significance of p-ATM expression by studying its ability to independently predict patient survival, using multivariate Cox regression analysis. We used p-ATM, age, AJCC stage and gender as a variables 
and analyzed the survival of the individuals. p-ATM was categorized as adverse to moderate vs strong, age as 60 vs 60, AJCC as 1801747-11-4 stages I & II vs stages III & IV, and gender as male vs female. As illustrated in Table 2, p-ATM was found to be significantly associated with 5-year survival, but not with 10-year survival of patients.
Melanoma is one of the most commonly diagnosed cancers in fair skinned populations as shown by the recent report from the USA ranking it as the fifth most common cancer in men and seventh most common cancer in women [44]. Patients with advanced stages of melanoma have a very low survival rate (15%) and an overall survival duration amongst 8 to 18 months [44]. There are only a few treatment options available for metastatic melanoma due to its resistance to conventional chemo and radiotherapy [389]. The success of available treatment options is also limited with effectiveness restricted to a subset of sufferers, development of lethal resistance, or only a small increase in median survival time [389]. Consequently, the search for alternative drugs is ongoing. Among the various origins of cancer, genomic instability is recognized as one of the major causes and UV radiation, a well-known genotoxic agent, is considered as one of the leading causes of melanoma [34, 45]. Previous studies identified that expression of several proteins involved in DNA repair were decreased or lost in melanoma sufferers, and that the loss of expression significantly correlated with poor patient survival [258, 31]. Our results here are partly in line with the previous data suggesting that a loss of mechanisms maintaining genomic integrity could be one of the critical events in melanoma pathogenesis. The significance of ATM in cancer progression and patient prognosis has been shown in studies on tissue samples from gastric, pancreatic, bladder and endometrial cancers [190, 22, 468]. Previous studies on nodular metastatic melanoma samples showed an upregulation of ATM at both transcript and protein levels [24]. The sample size in that study was relatively low and the study did not report any association amongst ATM expression and patient survival. The study also did not analyze p-ATM expression in melanoma sufferers. Moreover, very few studies reported the relationship among p-ATM expression and patient survival [23]. 21593435 Since ATM is a kinase, and its activation by phosphorylation at ser-1981 position allows it to associate itself with other DNA repair proteins as well as its down stream targets, analyzing p-ATM expression in individuals could yield more accurate results [1, 3, 33, 40]. Accordingly, our findings illustrate an association among p-ATM expression, melanoma progression, and patient survival. ATM has important functions in DNA repair and maintenance of genomic integrity and understandably, loss of ATM could be associated with initiation and cancer progression [49]. On the other hand, ATM mediated regulation of signalling cascades could also drive
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