A Multi-index Integral System Including P53, CyclinD1, HIF-1α Predicts Radiotherapy Sensitivity In NPC Patients

Objective:We screened the statistically significant index from five alternative index such as P53,CyclinD1,Ki67,HIF-1αand ATM, and then establish a multi-index integral system in order to predict the radiotherapy sensitivity of nasopharyngeal carcinoma(NPC).Methods:We investigated and selected retrospectively 30 pathological specimens of NPC patients who received radiotherapy. All of these patients were in xiangya second hospital from 2005 to 2010. And the pharynx nasalis of these patients were isocenter irradiated by 6MVX-Ray.The tumor dose of routine division were 70-80Gy/35-40 times. Cervical region were irradiated by 6MVX-Ray and electron-Ray,which totally dose were 50-66Gy,25-33times. The 30 patients were assigned to three groups by therapeutic effect for groupA(Radiation sensitive group), groupB(two years Recurrence group),groupC(Residual group). Each group included ten patients. All of these specimens were paraffin embeded. The pathological type of them were poorly differentiated squamous cell carcinoma. We observed tissue slice made from specimens by light microscope, staining with hematoxylin and eosin, then comfirmed pathologic diagnosis again. Five kinds of protein expression levels including P53,CyclinD1,Ki-67,HIF-1αand ATM in NPC pathology organization were tested by immunohistochemisty. All results were caculated in a statistic software(SPSS 13.0). We analyzed the correlation between five kinds of protein and radiotherapy sensitivity,and set up integrated system by protein expression levels. Then screened the statistically significant index to compose a integral system in order to predict the radiotherapy sensitivity in NPC.Finally we found the standard of the integral system is:P53 (-) 0; P53 (+) 1; P53 (++-～++) 2 HIF-1α(-) 0; HIF-1α(+) 1; HIF-1α(++～+++) 2 Cyclin D1 (-) 2; Cyclin D1 (+) 1; Cyclin D1 (++～+++) 0 Results:1.Compared among three groups, the level of P53 protein in group A was lower than group B (U=20.00,ρ<0.05), as well as group C (U=21.00,ρ<0.05), between group B and C there was no difference (U=40.50,ρ>0.05)2. Compared among three groups, the level of CyclinDl protein in group A was significantly higher than group B (U=24.50,ρ<0.05), and the same as group C (U=24.50,ρ<0.05), no difference was found between group B and C (U=47.00,ρ<0.05)3. Compared among three groups, the level of Ki-67 protein was no statistically significant differences between group A and B (U=50.00,ρ>0.05), no difference was found between group A and C either (U=46.00,ρ>0.05), the same as between group B and C (U=46.00,ρ>0.05).4. The level of HIF-1αprotein compared among three groups, in group A was lower than group B (U=23.50,ρ<0.05), and also lower than group C (U=19.00,ρ<0.05), between group B and C was no difference (U=45.00,ρ>0.05)5. Compared among three groups, there was no statistically significant differences of ATM protein between group A and B (U=50.00,ρ>0.05), also no difference between group A and C(U=36.00,ρ>0.05), in the same between group B and C (U=32.50,ρ>0.05).6. The integral mean value of group A was 1.80, in group B which was 4.00. In group C the integral mean value was 4.40. The total score compared among three groups by ANOVA, in group A was lower than group B((ρ<0.01), and also lower than group C(ρ<0.01), between group B and C there was no difference (U=0.308,ρ>0.05)Conclusion:1. Radiotherapy sensitivity was significantally lower in NPC patients whose P53 and HIF-1αexpressed higher. Radiotherapy sensitivity was significantally higher in NPC patients whose CyclinDl express higher.2. No significant relativeness was found with radiotherapy sensitivity either the level of ATM protein expression nor the Ki-67. 3.The radiotherapy sensitivity of NPC could be predicted by integral system preliminary. When the total value is less than three points, the radiotherapy sensitivity is higher. Vise versa, when the total value is more than three points, the radiotherapy sensitivity is lower.