Detection Of Circulating Tumor Cells From Peripheral Blood In Patients With Cervical Squamous Cell Carcinoma And Its Clinical Significance

Objective:This article explores the significance of detecting circulating tumor cells(CTCs)in patients with cervical squamous cell carcinoma,and analyzes the relationship between circulating tumor cell test results and clinicopathological factors as well as tumor markers.Also,the correlation among CTCs occurrence,invasion and metastasis of cervical squamous cell carcinoma is discussed,consequently providing theoretical basis for clinical application.Methods:From March 2019 to January 2020,a total of 132 research objects in Department of Gynaecology,the Affiliated Hospital of Qingdao University,was selected.There were 38 healthy people,12 lower-level cervical intraepithelial neoplasia and 38 high-level ones and 44 patients with early cervical squamous cell carcinoma.They were detected by using subtraction enrichment and immunostainingfluorescence in situ hybridization(SE-i FISH)technology.After that,we collected and sort out clinical and pathological information and biological test results of patients with cervical squamous cell carcinoma.We analyzed the correlation between the number of CTCs and the clinical information of patients’,such as age,FIGO stage,tumor differentiation,pelvic lymph node metastasis,lymphovascular space invasion(LVSI),cervical interstitial infiltration,para-uterine metastasis and squamous cell carcinoma-related antigen(SCC-Ag)level.We evaluated its correlation with pathological factors and clinical indicators comprehensively,and judged its clinical application value.Statistical analysis was processed by SPSS 25.0 software.Mann-Whitney U non-parametric test was performed for binary categorical variables.Grade data were compared and analyzed for multiple groups by Kruskal-Wallis non-parametric test.The Bonfferroni correction method was selected for comparison;the correlation between serum SCC-Ag and circulating tumor cells in peripheral blood was analyzed by Spearman’s rank correlation,and P<0.05 indicated that the difference was statistically significant.Results:The SE-i FISH technology was used to detect CTCs in patients with cervical squamous cell carcinoma,high-grade cervical intraepithelial neoplasia,low-grade cervical intraepithelial neoplasia,and healthy volunteers.It is found that the number of CTCs detected in the peripheral blood of different groups is different,which shows the statistical difference(P<0.001).We found the number of CTCs detected in 44 patients with cervical squamous cell carcinoma is more than any other group with median 9 cells/6ml;38 people with high-level intraepithelial neoplasia were detected the number of CTCs with the median4 cells/6ml in the peripheral blood;and similarly,the number of CTCs in peripheral blood in 12 people with low-level intraepithelial neoplasia and 38 normal people are 2 cells/6ml and 1 cells/6ml respectively.The number of CTCs detected in patients with cervical squamous cell carcinoma is significantly higher than that of healthy people,low-grade cervical intraepithelial neoplasia and high-grade cervical intraepithelial neoplasia patients(with all P<0.001).The number of CTCs detected in the cervical high-grade intraepithelial neoplasia group was significantly higher than that in the healthy control group(P=0.006).It may be related to the occurrence and development of cervical squamous cell carcinoma.It was found that there were significant differences in the number of CTCs in patients with pelvic lymph node metastasis(or vessel carcinoma embolus)VS non-pelvic lymph node metastasis(or non-pelvic lymph node metastasis)P=0.017(or P=0.043),and of course,they have significantly more CTCs than those without.The patients with pelvic lymph node metastasis have more CTCs than those without lymph node metastasis.The number of circulating tumor cells detected in peripheral blood increases as per FIGO stage.There is significant difference of the number of CTCs among patients in different stages,with P=0.017.Further,the number of CTCs detected in patients with stage III cervical cancer was significantly more than that in patients with stage I(P=0.038),while the tendency does not exist in other groups(P>0.05).However,the number of CTCs in the peripheral blood of patients who suffered from cervical cancer was not associated with age,cervical interstitial infiltration and degree of differentiation.The levels of SCC-Ag and were positively correlated with the number of CTCs in peripheral blood,with(r_s=0.728,P<0.001).Conclusion:1.The number of CTCs detected in patients with cervical squamous cell carcinoma is significantly higher than that of healthy people,low-grade cervical intraepithelial neoplasia and high-grade cervical intraepithelial neoplasia patients.It may be related to the invasion and metastasis of cervical squamous cell carcinoma.2.In our survey,the number of CTCs in cervical squamous cell carcinoma patients with pelvic lymph node metastasis and vascular tumor thrombus was higher than that of patients without pelvic lymph node metastasis;moreover,the number of CTCs in patients with cervical squamous cell carcinoma of LVSI is higher than that of patients without,which suggests CTCs might be correlated with the invasion and metastasis of cervical squamous cell carcinoma.3.The number of CTCs detected in patients with cervical squamous cell carcinoma is associated with FIGO stage.4.The levels of SCC-Ag and the number of CTCs were positively correlated,which illustrates that these factors play synergistic roles in the occurrence,progression and invasion of cervical squamous cell carcinoma.