The Expression And Clinical Significance Of Kr(?)ppel-like Factor 5 And Matrix Metalloproteinase-1 In Cervical Lesions

Objectives Cervical cancer is one of the most common gynecological cancer, the incidence rate increased year by year, and the trend was younger[1]. Kr(?)ppel like transcription factor 5, also known as BTEB2 and IKLF, belongs to KLF family. Recent researches have proved that KLF5 is related to the development of cervical cancer.Collagenase(including MMP-1, MMP-8, MMP-13) was mainly secreted by the tumor cells and stromal cells, which can degrade and modify the extracellular matrix and cell connection. MMP-1 is mainly acting on collgen Ⅰ,Ⅱ,Ⅲ,Ⅴand Ⅸ, which plays an important role in diverse physiologic processes such as development,tissue morphogenesis,and wound repair, which also in tumor′s occurrence an development. Our study was designed to detect the expression of KLF5 and MMP-1 in human cervical squmaous cell carcinoma tissues, and observe the changes of total collagen and different type of collagen,and to explore the relation between the expression KLF5, MMP-1 and cervical carcinogenesisi process, and to provide a scientific basis for clinical diagnosis and prognosis of cervical squmaous cell cancer.Methods Select patients who are from March 2013 to January 2016 in Tangshan Worker’s Hospital to cervical biopsy and surgical treatments, who have complete clinical data and did not receive preoperative radiotherapy and chemotherapy, a total of 134 cases,including parts of 48 cases of normal cervical tissues(Control group), 47 cases of high grade cervical neoplasia epithelium(HSIL group) and 39 cases of cervical squamous cell carcinoma(CSCC group). The patients’ general condition informations were collected by reviewing their electronic records. The protein level of KLF5 was semi-quantified by immuno-histochemical staining; the m RNA level of KLF5 and MMP-1were quantified by RT-q PCR; the deposition of total collagen was examined by Masson trichrome staining and the protein levels of collagen type Ⅰ, type Ⅱ and type Ⅲ were analysed by Western blot; their relationship to clinicopathologic features of cervical cancer was analyzed by Spearman rank correlation coefficient.Results 1 Compared with the patients’ age, Obstetrical history, age at menarche,menstrual cycle, menstrual days, the number of abortions, smoking, drinking, the difference was not statistically significant(P>0.05). 2 Immunohistochemical staining showed nucleus brown particles, the percentage of positive staining area in different groups were Control(18.75 ± 2.81 %), HSIL(64.33 ± 3.52 %) and CSCC(71.79 ±8.02 %), the expression of KLF5 protein were gradually increased,and the difference were statistically significant(P<0.05). 3 RT-q PCR showed that the expression of KLF5 m RNA in Control(1.00±0.381), HSIL(2.12±0.560), CSCC(4.83±0.250) were gradually increased(P < 0.05), statistical differences between groups were significant(P < 0.05); the expression of MMP-1 m RNA in Control(1.00±0.310), HSIL((2.69±0.549), CSCC(6.53±0.821) were also gradually increased(P < 0.05), statistical differences between groups were significant(P<0.05); the expression of MMP-8 m RNA in different groups have no signification(P>0.05); the expression of MMP-13 in CSCC group(2.16±0.471)was higher than in Control group(1.00±0.45)(P<0.05), there were no statistical difference between in HSIL group and in Control group(P>0.05); there was a positive correlation between KLF5 m RNA and MMP-1 m RNA expression in HSIL( r=0.311,P=0.034) and CSCC(r=0.388,P =0.015). 4 Masson trichrome staining showed collagen progressively thickens, linearizes and stiffens in cervical cancer. 5 Western blot analysis showed collagen Type Ⅰ and Ⅲ were significantly increased in cancer group( P<0.05).6 Tumor pathological grading, depth of myometrial invasion, clinical stage and lymph node metastasis of clinical parameters were positively correlated with KLF5 and MMP-1m RNA expression( P<0.05).Conclusions 1 There were high expression of KLF5 and MMP-1 in the process of cervical lesions, and there was positive correlation between KLF5 and MMP-1 expression.2 There expression were positively correlated with tumor pathological grading, depth of myometrial invasion, clinical stage and lymph node metastasis of clinical parameters,and the expression of KLF5 was also positively correlated with patients’ age,overexpression of KLF5 and MMP-1 might play active roles during the process of occurrence, development, invasion and metastasis of CSCC. 3 In carcinogenesis of cervical cancer exists the collagen remodeling, the structure showed that collagen progressively thickens, linearizes, and the number showed the expression of collagen Ⅰ, Ⅲ increased;the occurrence of cervical cancer process is a process that is likely to occur fibrosis.