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Dave et al.                                                                                                                                                                                          Nibrin expression in OSCC

           Table 2: Univariate survival analysis (Kaplan-Meier survival function) of Nibrin expression
            Variable                          n      Patients relapsed or died, n (%)  Log-rank  df      P
            Relapse free survival
            Nibrin (total patients, n = 78)
              Weak                            38               15 (39)*             0.006       1      0.937
              Strong                          40               17 (42)*
            Nibrin (early stage patients, n = 35)
              Weak                            12                1 (8)*              3.884       1      0.049
              Strong                          23               10 (43)*
            Nibrin (advanced stage patients, n = 43)
              Weak                            26               14 (54)*             0.593       1      0.441
              Strong                          17               7 (41)*
            Overall survival
            Nibrin (total patients, n = 90)
              Weak                            42               19 (45)#             0.112       1      0.737
              Strong                          48               20 (42)#
            Nibrin (early stage patients, n = 38)
              Weak                            13               2 (15)#              0.659       1      0.417
              Strong                          25               7 (28)#
            Nibrin (advanced stage patients, n = 52)
              Weak                            29               17 (59)#             0.010       1      0.920
              Strong                          23               13 (56)#
           *: patients relapsed; #: patients died

           difference in Nibrin expression between OSCC tissues   Plisiecka-Halasa et al.  also showed that in human
                                                                                  [25]
           and their corresponding adjacent normal tissues (t =   ovarian tumor tissues Nibrin expression was marked
           -0.455, df = 99, P = 0.657). Along with that in OSCC   as strong nuclear staining which was present in both
           tissues, Nibrin expression was significantly positively   tumors and normal tissues. Further, Nibrin expression
           correlated  with  tumor  differentiation  and  significantly   is up-regulated in adjacent  normal tissues of OSCC
           inversely correlated with tumor size and tumor stage,   tissue which is  compatible with the hypothesis that
                                                                                             [32]
           suggesting  that up-regulation  of Nibrin may be an   Nibrin is a tumor suppressor gene.  In contrast with
                                                                                    [30]
           early event in OSCC development. In accordance     our  findings,  Hsu  et al.  showed that Nibrin  over
                                                              expression was significantly correlated with high tumor
           with our results, Ali-Fehmi  et al.  also showed  that   size and metastatic dieses  in OSCC patients which
                                         [31]
           NBS1 does not show  markedly higher  expression  in   may be because of the inclusion of more number of
           all ovarian cancer patients compared to women with   patients with locally advanced diseases. Ehlers et al.
                                                                                                            [33]
           serous cyst adenoma and those with normal ovaries.   also showed  that Nibrin  was associated  with strong
                                                              tumor severity and metastatic death marker in uveal
                                                              melanoma. However,  similar  expression of  NBS1
                                                              in class 1 tumors and normal uveal melanocytes
                                                              suggests that up-regulation  of  NBS1 may be a late
                                                              event in melanoma progression.

                                                              Kaplan-Meier  univariate  survival  analysis  showed
                                                              that in patients with early stage disease high number
                                                              of patients relapsed with strong Nibrin  expression.
                                                              However,  our  findings  not  only  observed  increased
                                                              expression pattern  of  Nibrin  in early stage patients
                                                              but also found a strong correlation between increased
                                                              Nibrin expressions in the onset of the disease with
                                                              higher probability  of  recurrence.  This could be
                                                              attributed to the fact that since Nibrin acts as a sensor
                                                              molecule of MRN complex which further activates the
                                                              other DNA repair molecules, it might have a plausible
           Figure 2: Kaplan-Meier univariate survival analysis of patients with   role in constitutively activating these downstream
           early stage disease indicating significant high incidence of disease
           relapse in patients with strong Nibrin expression (P = 0.049). RFS:   molecules eventually leading  to  disease relapse
                                                                                        [30]
           relapse-free survival                              in patients.  While Hsu  et  al.   found that in OSCC
            440                                                             Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ November 25, 2016
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