High-risk human papillomavirus infection associated with telomere elongation in patients with esophageal squamous cell carcinoma with poor prognosis.
BACKGROUND
Telomere maintenance is crucial in carcinogenesis and tumor progression. The results of a previous study from the authors indicated that infection with high-risk human papillomavirus (HR-HPV) types 16, 18, and 58 was a risk factor for esophageal squamous cell carcinoma (ESCC) in the Shantou region of China. In the current study, the authors explored the association between HR-HPV infection, telomere length (TL), and DNA methylation and their significance in the prognosis of patients with ESCC.


METHODS
TL and DNA methylation were analyzed by real-time polymerase chain reaction and methylation-specific polymerase chain reaction in 70 cases of ESCC tumor (T) and paired nontumor (NT) tissues and 50 cases of normal esophagus (NE). The prognostic value of TL and DNA methylation in ESCC was analyzed.


RESULTS
TL gradually decreased from NE to NT to T tissue. TL in tumor tissue (T-TL) was found to be longer in tissue that was positive for HR-HPV compared with negative tissue and was found to be positively associated with viral load (Spearman correlation, 0.410; P = .037) and integration (represented by the ratio of HR-HPV E2 to E6/E7 genes; P = .01). The DNA methylation ratio of human telomerase reverse transcriptase was more prevalent with long (≥ 0.7) compared with short (< 0.7) T-TL and was positively correlated with T-TL (Spearman correlation, 0.318; P = .007) and HR-HPV integration (P = .036). Furthermore, Cox proportional hazards modeling revealed a high ratio of T-TL to NT-TL (≥ 0.80) as a factor of poor prognosis, independent of other clinicopathologic variables.


CONCLUSIONS
HR-HPV infection and integration related to telomere elongation and DNA methylation of human telomerase reverse transcriptase may be a potential biomarker of prognosis in patients with ESCC.
Department of Clinical Laboratory, Peking Union Medical College Hospital and Peking Union Medical College, Beijing, China.
Dong-Hong
DH
Zhang
Jiong-Yu
JY
Chen
Chao-Qun
CQ
Hong
De-Qing
DQ
Yi
Fei
F
Wang
Wei
W
Cui
D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000821:virology*; D019175:DNA Methylation; D004938:Esophageal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000821:virology*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D018628:Gene Dosage; D054884:Host-Pathogen Interactions; D052162:Human papillomavirus 16 / Q000502:physiology*; D052161:Human papillomavirus 18 / Q000502:physiology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000235:genetics / Q000473:pathology / Q000821:virology*; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D019098:Telomerase / Q000235:genetics; D016615:Telomere / Q000235:genetics / Q000378:metabolism / Q000821:virology; D059505:Telomere Homeostasis; D035341:Telomeric Repeat Binding Protein 2 / Q000235:genetics
C504753:TERF2 protein, human; D035341:Telomeric Repeat Binding Protein 2; C509186:TERT protein, human; D019098:Telomerase
DNA methylation; esophageal squamous cell carcinoma; human papillomavirus; prognosis; telomere length