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Contralateral upper tract urothelial carcinoma after nephroureterectomy: the predictive role of DNA methylation.

Zhang L, Xiong G, Fang D, Li X, Liu J, Ci W, Zhao W, Singla N, He Z, Zhou L - J. Exp. Clin. Cancer Res. (2015)

Bottom Line: High MI (P = 0.007) was significantly correlated with poor cancer-specific survival.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, National Urological Cancer Center, No. 8 Xishiku St, Xicheng District, Beijing, 100034, China. zl070501@126.com.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Estimated contralateral UTUC-free Kaplan-Meier survival curves stratified by methylation status of RASSF1A (A,P = 0.019), renal transplant history (B,P < 0.001), preoperative renal function (C,P < 0.001), bladder recurrence (D,P = 0.032).
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Fig2: Estimated contralateral UTUC-free Kaplan-Meier survival curves stratified by methylation status of RASSF1A (A,P = 0.019), renal transplant history (B,P < 0.001), preoperative renal function (C,P < 0.001), bladder recurrence (D,P = 0.032).

Mentions: Univariate analysis and multivariate analysis for contralateral UTUC recurrence after RNU is summarized in Tables 5 and 6, respectively. In multivariate analysis, unmethylated RASSF1A (P = 0.039, Figure 2A), renal transplant history (P < 0.001, Figure 2B), preoperative renal insufficiency (P = 0.002, Figure 2C), and lack of bladder recurrence before the development of contralateral UTUC (P = 0.007, Figure 2D) were found to be independent risk factors of contralateral UTUC recurrence after RNU.Table 5


Contralateral upper tract urothelial carcinoma after nephroureterectomy: the predictive role of DNA methylation.

Zhang L, Xiong G, Fang D, Li X, Liu J, Ci W, Zhao W, Singla N, He Z, Zhou L - J. Exp. Clin. Cancer Res. (2015)

Estimated contralateral UTUC-free Kaplan-Meier survival curves stratified by methylation status of RASSF1A (A,P = 0.019), renal transplant history (B,P < 0.001), preoperative renal function (C,P < 0.001), bladder recurrence (D,P = 0.032).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4307673&req=5

Fig2: Estimated contralateral UTUC-free Kaplan-Meier survival curves stratified by methylation status of RASSF1A (A,P = 0.019), renal transplant history (B,P < 0.001), preoperative renal function (C,P < 0.001), bladder recurrence (D,P = 0.032).
Mentions: Univariate analysis and multivariate analysis for contralateral UTUC recurrence after RNU is summarized in Tables 5 and 6, respectively. In multivariate analysis, unmethylated RASSF1A (P = 0.039, Figure 2A), renal transplant history (P < 0.001, Figure 2B), preoperative renal insufficiency (P = 0.002, Figure 2C), and lack of bladder recurrence before the development of contralateral UTUC (P = 0.007, Figure 2D) were found to be independent risk factors of contralateral UTUC recurrence after RNU.Table 5

Bottom Line: High MI (P = 0.007) was significantly correlated with poor cancer-specific survival.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, National Urological Cancer Center, No. 8 Xishiku St, Xicheng District, Beijing, 100034, China. zl070501@126.com.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus