The Expression Of HPV And TSLC1 In Cervical Lesions

Objective: Cervical cancer is one of the major cause of cancer-related mortality diseases in women. Infection with high-risk (i.e., carcinogenic) human papillomavirus (HR-HPV) types is causally involved in the onset of cervical carcinogenesis. and high-risk HPV DNA can be detected in almost all cervical carcinomas. To date, different HPV types have been associated with the development of cervical cancer and have been classified as high-risk or low-risk HPV types. High risk human papillomavirus especially HPV16 have direct bearing on the occurrence of cervical carcinomas. The cancer gene products of HPV 16E6/E7 often lead to the inactivation, variation and abnormal expression of cell gene during causing the cervical epithelium cell's immortality. But the carsinogenesis does not be interpreted totally now. The subsequent progression from premalignant cervical intraepithelial neoplasia (CIN) to invasive cancer is driven by both genetic and epigenetic processes. The relationship between cell apoptosis and tumor is hot study spot over the past several years. Recently, The adhesion molecule has close relation with the occurrence, development and prognosis of tumor. In which encoding a member of the immunoglobulin superfamily was named TSLC1 (tumor suppressor in lung cancer 1) and was identified as a tumor suppressor gene on chromosome 11q23.2 in NSCLC(non-small cell lung cancer) and the cancer cell growth was significantly suppressed. Through the suppression of tumor formation implying its involvement in various human cancers. Encoding an immunoglobulin (Ig)–like cell-surface glycoprotein protein that belongs to the family of Nectin and Nectin-like (Necl) molecules and is called Necl-2. The significant homology of its extracellular domain with those of other Ig superfamily cell adhesion molecules (IgCAMs),Loss of TSLC1 expression was strongly correlated with the promoter hypermethylation and loss of heterozygosity (LOH) in non-small cell lung cancer and other various epithelial tumours. In addition,The loss or reduction of TSLC1 expression was associated with a poor prognosis, indicating that the TSLC1 represents a central effector gene for controlling the biological aggressiveness of the tumor and that it is an essential biomarker for predicting the patient's prognosis. But the molecule mechanism of the tumor suppressor in cancers remain unclear.The research focused on the interdependencies by checking the gene expression of HPV 16E6/E7 and TSLC1 during cervical carcinomas or before cervical carcinomas, and explored the cause mechanism of cervical carcinomas further.Methods: 74 cases at surgical removal and cervical biopsy under colposcopy were obtained at gynecology in the secong hospital from 2005 to 2006. All the specimen have been confirmed by pathology, the 25 cases of them were CIN I , 22 cases were CINⅡ～Ⅲand 27 cases were invasive carcinoma of cervix uteri. 15 normal cervical tissues were chosen as comparison (hysterectomy specimen form uterine leiomyoma). The cervical carcinomas patients did not be treated by radiotherapy,chemotherapy. Histological type: 22 Squamous carcinoma, 5 Adenocarcinoma; Grading: 12 cases were high differentiated, 10 cases were moderate differentiated and the low one were 5. Stage of disease was determined according to FIGO criteria in1995: 14 cases were in I stage, 9 cases were in II stage , 4 cases were inⅢ～Ⅳstage. RT-PCR method was used to test the expression of HPV16E6/E7 and TSLC1 gene.The statistical software SPSS11.5 was used to analyze the data.Results: (1) The expression level of HPV16E6/E7 gene was in normal cervical group, CIN I, CINⅡ～Ⅲand cervical carcinomas group were 0.368±0.102,0.447±0.113,0.761±0.122,0.839±0.187 respectively. The increasing trends were showed. The expression of HPV16E6/E7 in cervical carcinomas group were higher than that in CIN groups, CIN groups was higher than that in normal cervical group; CINⅡ～Ⅲgroups was higher than that in CINⅠgroup, Differences were considered to be statistically significant at P<0.05. (P<0.05). But differences were not considered to be statistically significant between normal cervical group and CINⅠgroup, between CINⅡ～Ⅲgroup and cervical carcinomas group (P>0.05). (2) The relations between the expression level of HPV16E6/E7 gene and the cervical carcinomas clinical pathology parameter: Differences were not considered to be statistically significant between the expression level of HPV16E6/E7 and the different Age Groups, clinical stages, histology grades and histology types in cervical carcinomas (P>0.05). (3) The expression level of TSLC1 gene in normal cervical group, CIN I, CINⅡ～Ⅲand cervical carcinomas group were 0.917±0.143,0.819±0.36,0.727±0.180,0.639±0.178 respectively,the decreasing trend was showed. The normal cervical group was higher than that in CINⅡ～Ⅲgroups and cervical carcinomas group,CINⅠgroup was higher than that in cervical carcinomas group,Differences were considered to be statistically significant (P<0.05);But differences were not considered to be statistically significant between normal cervical group and CINⅠgroup, between CINⅠgroup and CINⅡ～Ⅲgroup, between CINⅡ～Ⅲgroup and cervical carcinomas group (P>0.05). (4) The relations between the expression level of TSLC1 gene and the cervical carcinomas clinical pathology parameter:in low differentiateed cervical carcinomas organization,the expression level of TSLC1 gene was significantly lower than that in high,moderate differentiated cervical carcinomas organization, Differences were considered to be statistically significant (P<0.05), Differences were not considered to be statistically significant between the expression level of TSLC1 gene and the different Age Groups, clinical stages, histology grades and histology types in cervical carcinomas (P>0.05). (5) The relativity between HPV16E6/E7 and TSLC1 gene in cervical carcinomas group:The expression level of HPV16E6/E7 was not relativly with that of TSLC1 gene,the correlation coefficient r=0.281,Differences were considered to be statistically significant at P>0.05.Conclusion: (1) The expression level of HPV16E6/E7 gene is closely relative with the development of cervical lesions.(2)TSLC1 gene levels is expressed in normal cervical biopsy,TSLC1 gene silencing is a frequent event in the progression from high-risk HPV–containing high-grade CIN lesions to invasive cervical cancer. (3) The HPV16E6/E7,TSLC1 gene might show a synergistic effect during the occurrence and development of cervical carcinomas, indicated the two gene has important reference value for clinical earlier diagnosis of cervical carcinomas and judgment prognosis. (4) TSLC1 silencing is likely to be associated with the transition from an immortal to a tumorigenic phenotype. TSLC1 gene provides theory foundation for curing cervical lesions.