title: The relationship between HPV16 and expression of cyclooxygenase-2, P53 and their prognostic roles in esophageal squamous cell carcinoma.
abstract: OBJECTIVE
  This study aimed to investigate the relationship between human papillomavirus type 16 (HPV16) and expression of cyclooxygenase-2 (COX-2), P53 in esophageal squamous cell carcinoma (ESCC), which has not yet been elucidated.
  
  
  METHODS
  HPV16 was detected by amplifying the HPV16 E6 gene by the PCR method, and the expression of COX-2, P53 protein in 69 ESCCs and 32 normal esophageal mucosa (NEM) from Shaanxi Province was examined by the streptavidin-peroxidase method. Estimation of overall survival by HPV16, COX-2, and P53 was calculated with the Kaplan-Meier method and analyzed with the log-rank test.
  
  
  RESULTS
  The infection rate of HPV16 in ESCCs (35 of 69, 50.7%) was significantly higher than that in NEMs (two of 32, 6.25%) (P<0.01). The expression rate of COX-2 in ESCCs (44 of 69, 63.8%) was higher than that in NEMs (two of 32, 6.25%) (P<0.01). The expression intensity of COX-2 expression had statistical difference in histological grade (R = 0.4453, P = 0.0019), tumor stage (R = 0.438, P = 0.000), and metastasis (R = 0.417, P = 0.002). P53 expression rate was 49.3% (34 of 69) in ESCC and 18.8% (six of 32) in NEMs. The expression rate of P53 proteins in ESCC was statistically higher than that in N67EMs (P = 0.0037). The infection of HPV16 had inverse correlation with the overexpression of COX-2 in ESCCs (R = -0.321, P = 0.008). The HPV16 DNA in ESCC had no statistical correlation with P53 protein (R = -0.014, P = 0.9055) and the elevated expression of COX-2 had positive correlation with P53 protein in ESCC (R = 0.441, P = 0.000). No statistical correlation was observed between the infection of HPV16 and clinicopathological features in ESCCs including sex, age, tumor stage, and lymph node metastasis, respectively (P>0.05). The COX-2 had no statistical correlation with sex and age (P>0.05), but had association with tumor stage and lymph node metastasis, respectively (P<0.05). The expression of P53 protein had significant association with lymph node metastasis (P = 0.0005), but not with sex, age, and tumor stage, respectively (P>0.05). The overexpression of COX-2, infection of HPV16, and P53 protein in ESCC were not correlated with survival during the 5-year follow-up period (P>0.05).
  
  
  CONCLUSIONS
  We first concluded that the increased expression of COX-2 had inverse correlation with HPV16 in ESCC. COX-2, HPV16, and P53 had no significant effect on the survival of patients with ESCC. These observations might help us to further understand the significant association between HPV16 and other molecules involved in the carcinogenesis and progression of ESCC.
authors.affiliation: The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science & Technology, Xi'an Jiaotong University, Xi'an, Shaanxi Province 710048, China. lwk2001@263.net
authors.forename: Wen-Kang
authors.initials: WK
authors.lastname: Liu
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Jiang
authors.forename: Mei-Ping
authors.initials: MP
authors.lastname: Zhang
authors.forename: Zhen-Xi
authors.initials: ZX
authors.lastname: Zhang
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000556:secondary / Q000821:virology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004279:DNA, Viral / Q000032:analysis; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D005260:Female; D052162:Human papillomavirus 16 / Q000302:isolation & purification*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D009367:Neoplasm Staging; D030361:Papillomavirus Infections / Q000150:complications*; D011379:Prognosis; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D004279:DNA, Viral; D016159:Tumor Suppressor Protein p53; D051546:Cyclooxygenase 2