|Contralateral upper tract urothelial carcinoma after nephroureterectomy: the predictive role of DNA methylation|
|Zhang, Lei1; Xiong, Gengyan1; Fang, Dong1; Li, Xuesong1; Liu, Jin1; Ci, Weimin2; Zhao, Wei3; Singla, Nirmish4; He, Zhisong1; Zhou, Liqun1|
|关键词||Methylation Upper Tract Urothelial Carcinoma Contralateral Recurrence Radical Nephroureterectomy Predictors|
|刊名||JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH|
|WOS标题词||Science & Technology|
|关键词[WOS]||UPPER URINARY-TRACT ; TRANSITIONAL-CELL-CARCINOMA ; INVASIVE BLADDER-CANCER ; PROMOTER HYPERMETHYLATION ; RENAL PELVIS ; TUMORS ; NEPHROPATHY ; ASSOCIATION ; EXPRESSION ; PROGNOSIS|
Background: Aberrant methylation of genes is one of the most common epigenetic modifications involved in the development of urothelial carcinoma. However, it is unknown the predictive role of methylation to contralateral new upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). We retrospectively investigated the predictive role of DNA methylation and other clinicopathological factors in the contralateral upper tract urothelial carcinoma (UTUC) recurrence after radical nephroureterectomy (RNU) in a large single-center cohort of patients.
Methods: In a retrospective design, methylation of 10 genes was analyzed on tumor specimens belonging to 664 consecutive patients treated by RNU for primary UTUC. Median follow-up was 48 mo (range: 3-144 mo). Gene methylation was accessed by methylation-sensitive polymerase chain reaction, and we calculated the methylation index (MI), a reflection of the extent of methylation. The log-rank test and Cox regression were used to identify the predictor of contralateral UTUC recurrence.
Results: Thirty (4.5%) patients developed a subsequent contralateral UTUC after a median follow-up time of 27.5 (range: 2-139) months. Promoter methylation for at least one gene promoter locus was present in 88.9% of UTUC. Fewer methylation and lower MI (P = 0.001) were seen in the tumors with contralateral UTUC recurrence than the tumors without contralateral recurrence. High MI (P = 0.007) was significantly correlated with poor cancer-specific survival. Multivariate analysis indicated that unmethylated RASSF1A (P = 0.039), lack of bladder recurrence prior to contralateral UTUC (P = 0.009), history of renal transplantation (P < 0.001), and preoperative renal insufficiency (P = 0.002) are independent risk factors for contralateral UTUC recurrence after RNU.
Conclusions: Our data suggest a potential role of DNA methylation in predicting contralateral UTUC recurrence after RNU. Such information could help identify patients at high risk of new contralateral UTUC recurrence after RNU who need close surveillance during follow up.
|项目编号||BMU20120318 ; 7122183 ; 81172419 ; 81372746|
|资助机构||Collaborative Research Foundation of Peking University Health Science Center ; College of Medicine ; Natural Science Foundation of Beijing ; Natural Science Foundation of China ; Research Foundation of Peking University First Hospital ; National Taiwan University|
|作者单位||1.Peking Univ, Hosp 1, Inst Urol, Natl Urol Canc Ctr,Dept Urol, Beijing 100034, Peoples R China|
2.Chinese Acad Sci, Beijing Inst Genom, Beijing 100101, Peoples R China
3.Peking Univ, Canc Hosp & Inst, Minist Educ, Dept Cell Biol,Key Lab Carcinogenesis & Translat, Beijing 100142, Peoples R China
4.Univ Texas SW Med Ctr Dallas, Dept Urol, Dallas, TX 75390 USA
|Zhang, Lei,Xiong, Gengyan,Fang, Dong,et al. Contralateral upper tract urothelial carcinoma after nephroureterectomy: the predictive role of DNA methylation[J]. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,2015,34.|
|APA||Zhang, Lei.,Xiong, Gengyan.,Fang, Dong.,Li, Xuesong.,Liu, Jin.,...&Zhou, Liqun.(2015).Contralateral upper tract urothelial carcinoma after nephroureterectomy: the predictive role of DNA methylation.JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,34.|
|MLA||Zhang, Lei,et al."Contralateral upper tract urothelial carcinoma after nephroureterectomy: the predictive role of DNA methylation".JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 34(2015).|