| Objective: Lung cancer was the most common malignant tumor in the world, of which the morbidity and mortality is the fastest growing,and was one of the greatest threats of malignant tumor to human health and life. The non small cell lung cancer(NSCLC) accounted for 80% of all lung cancer. In the process of treatment, founding tumor markers with strong specificity and high sensitivity, contributed to the early detection of disease, early diagnosis and subsequent specific targeted therapy. Protein tyrosine phosphatase(PTP) played an important role in the human body physiological, pathological processes, which controlled the dynamic balance of phosphorylation and dephosphorylation in vivo. And this balance was crucial to maintain the body’s normal physiological function.When this balance was broken, it would cause the body’s normal physiological function abnormal, then lead to disease. Regeneration of liver cell phosphatase family was a subgroup of protein tyrosine phosphatase family, as well as protein tyrosine phospholipid, which widely participated variety of physiological and pathological behaviors in the body. In recent years, PTP was been widely concerned because it played an important role in the malignant biological behavior of the tumor such as metastasis, tumor cell invasion. The phosphatases of regenerating liver 1(PRL-1, also known as protein tyrosine phosphatase type IVA,member 1, PTP4A1) was a member of the family of Liver cell regeneration phosphatase. The study found that PTP4A1 could promote tumor cell invasion and metastasis when it was high expression in a variety of solid tumors and tumor cell lines. The expression level of PTP4A1 was related with the malignant degree of tumor cells and its malignant biological behavior. But the report was less on the expression of PTP4A1 in non small cell lung cancer. By studying the expression of PTP4A1 molecule in non small cell lung cancer tissues, and analyzing the relationship between the expression level and tumor invasion, metastasis and the overall survival and relapse rate of patients, the purpose of the experiment was to provide certain theoretical basis for the clinical pathology diagnosis and prognosis estimation for non small cell lung cancer and provide a new idea for its specific molecular target therapy research.Methods: All the tumor tissue specimens and the corresponding part of para-carcinoma tissue and normal tissue specimens of 150 patients with non small cell lung cancer underwent operation treatment in department of thoracic surgery, the fourth hospital of Hebei medical university between January 2006 and January 2014 were collected and made into tissue microarray. Among them, 89 cases of patients with adenocarcinoma and 61 cases of patients with squamous carcinoma; male 115 cases, female 35 cases; age 34-78 years old, mean age 57.96 ± 8.45 years old; according to histological grading: 7 cases with well-differentiated(I), 96 cases with moderately differentiated(II), 47 cases with poorly differentiated(III); according to clinical stage: 32 patients with stage IA, stage IB 40 cases, stage IIA 38 cases, stage IIB10 cases, stage IIIA 29 cases and stage IIIB 1 cases; 50 patients with Lymph node metastasis and 100 patients without lymph node metastasis. The expression of PTP4A1 in different tissues was detected by immunohistochemistry and tissue microarray technology. And then analyze the relationship between PTP4A1 expression and clinical pathological parameters.The SPSS19.0 statistical software package was used for statistical analysis. Measurement data was expressed as mean ±standard deviation, and the comparison of positive rate was use of x2 test; The Kaplan- Meire method was used for single factor analysis, and the log-rank method was used for examining the relationship between the 9 factors and the expression level of PTP4A1. For the variable with stronger professional significance and the variable with statistical significance through single factor analysis, they were incorporated into the Cox proportional regression hazard model for further analysis.Results : The differences of the expression level of PTP4A1 in different tissues specimens of patients with lung cancer were statistically significant.( x2=7.738, P=0.025<0.05). Further more, though pairwise comparison, it showed that the difference between tumor tissue and nomal tissue was statistically significant(x2= 6.946, P=0.008 <0.0125), but there was no significant difference between tumor tissue and para-carcinoma tissue( x2= 0.097, P=0.341 >0.0125) and there was no significant difference between para-carcinoma tissue and nomal tissue(x2=1.905, P=0.168 >0.0125).The statistical analysis between the expression level of PTP4A1 and various clinical parameters showed that the expression level of PTP4A1 was correlated with metastasis of lymph node, the expression of PTP4A1 was higher for patients with lymph node metastasis higher compared with patients without lymph node metastasis, the difference was statistically significant(P=0.011<0.05). And the expression of PTP4A1 in late stage patients was higher than that in early stage patients, the difference was statistically significant(P=0.022<0.05). But there were no significant differences between the expression of PTP4A1 and other clinical parameters such as age, gender, pathological classification, degree of differentiation and smoking history(P>0.05).In these 150 patients, we made a single factor analysis between the expression of PTP4A1 and the survival rate and recurrence rate. The results showed that,the overall survival rate of PTP4A1 high expression group was lower than that of PTP4A1 low expression group(P=0. 006<0. 05), but the recurrence rate was higher than that of PTP4A1 low expression group(P=0. 014<0. 05). In order to further verify the results, the variable with statistical significance through single factor analysis was incorporated into the Cox proportional regression hazard model. The results showed that, the overexpression of PTP4A1 was the high risk factors affecting postoperative survival time( HR=1.660, 95%CI: 1.016-2.712, P=0. 043). In addition, the tissue differential degree, pathologic type and lymph node metastasis were also the high risk factors affecting postoperative survival rate and recurrence rate.Conclusions: PTP4A1 protein molecule is expressed in both tumor tissue and normal tissue, but the expression of which in tumor tissues is higher than that of the normal tissues, this suggests that it may play a role in the occurrence, development process of NSCLC.The expression level of PTP4A1 was correlated with clinical staging and lymph node metastasis of NSCLC. PTP4A1 is the high risk factor affecting postoperative overall survival rate and recurrence rate. The above results provide new evidence what suggests that PTP4A1 protein molecules may be involved in malignant transformation of tumor cells and theirs invasion, metastasis, which indicate that it not only can be used as reference index of prognosis estimation, but also it is expected to become a new study target in the gene therapy of NSCLC.There is no significant difference of PTP4A1 expression between adenocarcinoma and squamous cell carcinoma, which suggests that PTP4A1 cannot be used as the identification index of carcinoma and squamous cell carcinoma.Tissue microarray technology has the advantages of high information content, small volume and so on, and can improve the efficiency, save the cost and reduce the error, which has an obvious advantage in the large sample study. |
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