Expression Of GRO-1, HGF, PDGF-AA And SE-selectin In Serum Of Cervical Squamous Cell Carcinoma And Their Correlation With High Risk HPV Infection

Objective:1.To explore the positive rate of high-risk Human Papillomavirus in the CSCC patients and the CIN patients.2. To investigate the relationship between high-risk HPV infection and clinicopathological variables.3. To detect the prognostic value of high-risk HPV infection in the CSCC patients.Methods:A total of426cases were enrolled in our study, of which292cases were patients with CSCC,43were cervical intraepithelial neoplasia (CIN) patients and91were healthy controls. Two-channel fluorescent real time PCR was used to determine HPV DNA in cervical scrapings of CSCC and CIN patients.Results:1.The higher high-risk HPV infection was found in the CSCC patients compared with the CIN patients (P=0.013) and HPV16was the most common genotype in the CSCC patientsand the CIN patients.2. The high-risk HPV infection was not associated with age, FIGO stage, metastasis, grading, pelvic lymph node metastasis or tumor size of the CSCC patients (P>0.05).3. The HPV-positive patients had shorter OS and PFS compared with the HPV-negative patients (OS, P=0.027; PFS, P=0.023).Conclusion:The high infection rate was found in the CSCC patients, and it has some correlation with the prognosis of the patients with CSCC. Objective:1. To explore the differential expression of growth-regulated oncogene-1(GRO-1), hepatocyte growth factor (HGF), platelet-derived growth factor-AA (PDGF-AA) and soluble E-selectin (sE-selectin)in the serum of the CSCC patients, the CIN patients and the healthy controls.2. To investigate the relations of serum levels of GRO-1, HGF, PDGF-AA and sE-selectin with clincopathological variables in the CSCC patients.3. To detect the diagnostic value of GRO-1, HGF, PDGF-AA and sE-selectin in the CSCC patients.4. To explore the prognostic value of GRO-1, HGF, PDGF-AA and sE-selectin in the CSCC patients.Methods:Luminex xMAP technology was used to detect the serum levels of GRO-1, HGF, PDGF-AA and sE-selectin in the CSCC patients, the CIN patients and the healthy controls.Results:1. The serum levels of GRO-1in CSCC were significantly higher than those of the patients with CIN and the healthy controls (P<0.0001), and that the serum levels were associated with FIGO stage (P=0.001), metastasis (P<0.0001), pathological grading (P<0.0001)and pelvic lymph node metastasis(P=0.003).2. The serum levels of HGF in the CSCC patients significantly increased compared with the CIN patients and healthy controls, and that the serum levels were correlated with FIGO stage (P=0.02), pathological grade (P<0.0001), pelvic lymph node metastasis (P<0.0001), tumor size (P<0.0001) and HPV infection (P=0.039).3. There was no relationship of PDGF-AA between the CSCC patients and the other two groups. The concentrations of PDGF-AA in the serum of CSCC patients were correlated with FIGO stage (P=0.004), pathological grading (P=0.021) and pelvic lymph node metastasis (P<0.0001).4. The serum levels of sE-selectin significantly increased in the CSCC patients sE-selectin were correlated with age (P<0.0001), FIGO stage (P<0.0001) and tumor size (P=0.001).5. There were several positive correlations of the serum levels of HGF with the other three factors:serum levels of HGF was correlated with GRO-1(R=0.194, P=0.001), PDGF-AA (R=0.202, P=0.0005), sE-selectin (R=0.214, P=0.0002) and the concentrations of PDGF-AA was correlated with GRO-1(R=0.361, P<0.0001), while we could not find the relationships of sE-selectin with GRO-1(R=0.001, P=0.991) and PDGF-AA (R=-0.002, P=0.971).6. The receiver operating characteristic (ROC) curves showed that HGF obtained the highest diagnostic value compared with the other three factors.7. The log-rank analysis showed that low expression of GRO-1(<748.43pg/ml) had significantly longer OS and PFS than those with high expression of GRO-1(>748.43pg/ml)(OS, P=0.049; PFS, P=0.048), and that high expression of HGF (>724.35pg/ml) had significantly shorter OS and PFS than those with low expression of HGF (<724.35pg/ml)(OS, P<0.0001; PFS, P<0.0001), the analysis also indicated the significant differences of OS and PFS between the high (>22176.68pg/ml) and low expression (<22176.68pg/ml) of sE-selectin (OS, P=0.048; PFS, P=0.028), but we could not find the differences of OS and PFS between the high (>13311.48pg/ml) and low expression (<13311.48pg/ml) of PDGF-AA (OS, P=0.209; PFS, P=0.207).8. The multivariate Cox regression analysis showed that the serum levels of HGF (P<0.0001), FIGO stage (P<0.0001) and pelvic lymph node metastasis (P=0.001) were independent prognostic factors in the patients with CSCC, while high-risk HPV infection did not show any significance in this analysis.Conclusion:These results demonstrated that HGF may be a useful diagnostic and prognostic biomarker in the patients with CSCC, while high-risk HPV infection did not show any significance in this study.