International Journal of Hematology and Oncology 2019, Vol 29, Num 4 Page(s): 198-209
Deregulated Expression of SIRT3/FOXO3a/SOD2 Axis is Associated with Poor Survival in HNC Patients

Malik Waqar AHMED1, Azhar MEHMOOD1, Shazma GUL1, Anum KHURSHEED1, Faisal RAHMAN2, Mahmood Akhtar KAYANI1, Ishrat MAHJABEEN1

1COMSATS University Islamabad, Department of Biosciences, Islamabad, PAKISTAN
2Federal Govt Education Institution, Rawalpindi, Department of Statistics, Rawalpindi, PAKISTAN

Keywords: UPRmt genes, SIRT3, FOXO3a, SOD2, HNC
Current study was conducted to assess the expression variations of UPRmt genes such as SIRT3, FOXO3a and SOD2 in head and neck cancer (HNC). In present study 200 HNC tumors and adjacent uninvolved sections, taken as controls, were used. q-RT PCR was performed for expression analysis of selected genes in HNC. Data analysis showed significant down-regulation of SIRT3 (p< 0.0001) and significant up-regulation of FOXO3a (p< 0.0001) and SOD2 (p< 0.0001) in HNC tumors compared to control sections. Expression levels of selected genes were correlated using spearman correlation and SIRT3 showed significant negative association with SOD2 (r= -0.372; p< 0.02) and FOXO3a (r= -0.669; p< 0.01). A significant positive association was observed between the FOXO3a with SOD2 (r= 0.447**; p< 0.01) and SIRT3 with Ki-67 (r= 0.391; p< 0.02) in HNC patients. Kaplan-Meier analysis showed down regulation of SIRT3 (logrank p= 0.02, HR= 1.90, 95% CI= 1.63-2.21) and up-regulation of FOXO3a (logrank p= 0.03, HR= 1.88, 95% CI= 1.41-2.49) and SOD2 (logrank p= 0.0009, HR= 2.54, 95% CI= 1.31-4.90) was observed associated with decreased survival of HNC patients. These data suggest that deregulated expression of UPRmt genes act as the independent prognostic markers in HNC.