The Expression Of Polymerase Iota And Its Correlation With Clinicopathological And Prognosis Of Human Lung Cancer

[Background and Objective]Lung cancer is one of the most common malignant tumor in mankind. The morbidity and mortality of lung cancer have grown greatly in recent years all over the world. In the big cities of Europe, America and China, the incidence has taken the first place in every kind of male tumor statistically. The 5-year survival rate is lower than 15%, because the majority of patients with lung cancer were already in the progressive phase as they are diagnosed, and have missed the optimal surgery opportunity. The accurate molecular mechanism of lung cancer has not fully elucidated. Therefore it is of great importance to explore the formation, development and metastasis molecular mechanisms of lung cancer and create a convenient method for diagnosis and prevention at the gene level. The tumor molecular genetics research generally proved that the occurrence and development of lung cancer are a process involving multi-gene participation, multi-factor dysfunction, and its basic reason lies in the gene damage and unusual repair. The proto-oncogene, tumor suppressor gene, and the DNA repair gene are the so-called three tumor genes. All of them exist in the human normal cells, interact with each other, and maintain cell normal growth, differentiation, proliferation and function together. Activation of the proto-oncogene and deactivation of the anti-oncogene result in malfunction, and eventually the carcinoma occurs. Some studies indicate that besides activation of the proto-oncogene and deactivation of the anti-oncogene, the mutation of the DNA damage repair genes cause the dysfunction of the gene, and result in accumulation of DNA damage, the increased instability of the genome, and finally causes the mutation cell of the cell phenotype. So mutation of the DNA damage repair genes may be one of the most important molecular mechanisms which mediate the tumors occur.Poli gene is one of kind the DNA damage repair genes participating in the gene repair. Product of the gene is DNA polymerase Y family's member, namely the DNA polymerase Iota (Polymerase iota, Poli). In recent years the Poli gene studied in lung cancer draws of great concerns. Because the high mispairing tendency of Poli in the damage repair process, it is prone to induce gene mutations, the DNA damage's repair is important to maintained cell integrity, therefore it is important to study the DNA polymerase iota expression in the patients with lung cancer and its correlation with clinicopathological and prognosis. The goal of the research is to examine the expression of the DNA polymerase Iota in lung cancer patient tumor tissue, the tissue nearby and the normal control, and reveal the relationship among the Poli, clinicopathological and prognosis in patients with lung cancer. It can provide a theoretical basis in order to explore a new gene therapy targets.【Materials and Methods】62 patients treated at the Shandong University QiLu hospital from January,2001 to august 2003 were admitted in the study. All of the patients were with explicit pathological diagnosis of primary lung cancer, and without tradiotherapy and chemotherapy before the operation treatment. And 30 samples were taken from the tumor boundary 0.5 cm, tumor edge 5 cm the normal lung tissue were takes as the negative control. Immunochemisty and RT-PCR were applied to examine the Poli expression level. And each of the dyeing slice was read by experienced pathology doctor under the identical condition with the Olympus optical microscope using double blind method. Positive Poli protein dyings were yellow and yellowish brown in cytoplasma. Grading were carried out according to the dying intensity and the positive cell number. SPSS 13.0 software were used to make statistics analysis. P<0.05 were taken as having statistics significance.[Results]The expression rate of Poli protein in lung cancer tissue was 54.8%, the expression rate of the tissue nearby the cancer was 33.3%, in the normal lung tissue Poli the expression rate was 10.0%. Poli expression in lung cancer tissue and neighboring tissue was significantly higher than those in the normal lung tissue (x2=16.906,4.812, P<0.05); In the different pathological types Poli expression showed no differences(χ2=1.893, P>0.05); Among the different differentiated lung cancer Poli expression had the statistically difference, and Poli expression of the low differentiation stage was higher (x2=8.036, P<0.05); Poli expression of stage III and IV was obviously higher than those of stage I and II (χ2=9.389, P<0.05); Poli expression of survival rates below 3 years was higher than those above 3 years (χ2=4.987, P<0.05); Poli expression in the smokers was higher than in the non-smokers (χ2=6.120, P<0.05); Poli gene expression level is higher in the cancer tissue than nearby cancer tissue.【Conclusions】Poli expression level in the cancer tissue and neighboring tissue was statistically higher than in the normal lung tissue, suggesting that the high expression of Poll may play an important role in the occurrence and development of lung cancer. So possibly it could be applied as a biologic marker for diagnosis and prognosis of lung cancer. Expression of Poli in the tumor with different differentiation degree, different TNM stage were obviously different, and had a positive correlation, so Poli possibly played great roles in the lung cancer development and invasion, and produce huge influence on the prognosis of the lung cancer patient.