Prognostic Relevance of Methylenetetrahydrofolate Reductase Polymorphisms for Prostate Cancer.
Prognostic Relevance of Methylenetetrahydrofolate Reductase Polymorphisms for Prostate Cancer.
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亚甲基四氢叶酸还原酶多态性与前列腺癌的预后相关性。
DOI：
10.3390/ijms17121996
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发表时间：
2016-11-29
影响因子：
5.6
通讯作者：
Bao BY
中科院分区：
文献类型：
--
作者：
Lin VC;Lu TL;Yin HL;Yang SF;Lee YC;Liu CC;Huang CY;Yu CC;Chang TY;Huang SP;Bao BY
叶酸代谢通过核苷酸合成、DNA甲基化和DNA修复的改变与癌症相关。我们假设，亚甲基四氢叶酸还原酶（MTHFR），叶酸代谢的关键酶的遗传变异，将影响前列腺癌的预后。在458例接受根治性前列腺切除术的临床局限性前列腺癌患者中，对MTHFR基因区域的三个单倍型标记单核苷酸多态性（SNP）进行基因分型。一个SNP，rs9651118，与疾病复发相关，并且在调整已知风险因素的多变量分析后，这种关联仍然存在。公共数据集分析表明，rs9651118影响MTHFR表达。实时定量聚合酶链反应分析显示，MTHFR的表达显着上调前列腺肿瘤组织与相邻的正常组织相比。此外，在两个独立的公开可用的前列腺癌数据集中，MTHFR的过表达与癌症复发和死亡相关。总之，我们的数据提供了进一步验证MTHFR rs9651118作为前列腺癌预后生物标志物的临床效用的理论基础。
Folate metabolism has been associated with cancers via alterations in nucleotide synthesis, DNA methylation, and DNA repair. We hypothesized that genetic variants in methylenetetrahydrofolate reductase (MTHFR), a key enzyme of folate metabolism, would affect the prognosis of prostate cancer. Three haplotype-tagging single-nucleotide polymorphisms (SNPs) across the MTHFR gene region were genotyped in a cohort of 458 patients with clinically localized prostate cancer treated with radical prostatectomy. One SNP, rs9651118, was associated with disease recurrence, and the association persisted after multivariate analyses adjusting for known risk factors. Public dataset analyses suggested that rs9651118 affects MTHFR expression. Quantitative real-time polymerase chain reaction analysis revealed that MTHFR expression is significantly upregulated in prostate tumor tissues when compared with adjacent normal tissues. Furthermore, overexpression of MTHFR correlates with cancer recurrence and death in two independent publicly available prostate cancer datasets. In conclusion, our data provide rationale to further validate the clinical utility of MTHFR rs9651118 as a biomarker for prognosis in prostate cancer.
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来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
14.9
作者：
Ward LD;Kellis M
通讯作者：
Kellis M
影响因子：
4.5
作者：
Huang, Shu-Pin;Lan, Yu-Hsuan;Bao, Bo-Ying
通讯作者：
Bao, Bo-Ying
影响因子：
3.7
作者：
Nakagawa T;Kollmeyer TM;Morlan BW;Anderson SK;Bergstralh EJ;Davis BJ;Asmann YW;Klee GG;Ballman KV;Jenkins RB
通讯作者：
Jenkins RB
影响因子：
30.8
作者：
Lonsdale, John;Thomas, Jeffrey;Salvatore, Mike;Phillips, Rebecca;Lo, Edmund;Shad, Saboor;Hasz, Richard;Walters, Gary;Garcia, Fernando;Young, Nancy;Foster, Barbara;Moser, Mike;Karasik, Ellen;Gillard, Bryan;Ramsey, Kimberley;Sullivan, Susan;Bridge, Jason;Magazine, Harold;Syron, John;Fleming, Johnelle;Siminoff, Laura;Traino, Heather;Mosavel, Maghboeba;Barker, Laura;Jewell, Scott;Rohrer, Dan;Maxim, Dan;Filkins, Dana;Harbach, Philip;Cortadillo, Eddie;Berghuis, Bree;Turner, Lisa;Hudson, Eric;Feenstra, Kristin;Sobin, Leslie;Robb, James;Branton, Phillip;Korzeniewski, Greg;Shive, Charles;Tabor, David;Qi, Liqun;Groch, Kevin;Nampally, Sreenath;Buia, Steve;Zimmerman, Angela;Smith, Anna;Burges, Robin;Robinson, Karna;Valentino, Kim;Bradbury, Deborah;Cosentino, Mark;Diaz-Mayoral, Norma;Kennedy, Mary;Engel, Theresa;Williams, Penelope;Erickson, Kenyon;Ardlie, Kristin;Winckler, Wendy;Getz, Gad;DeLuca, David;MacArthur, Daniel;Kellis, Manolis;Thomson, Alexander;Young, Taylor;Gelfand, Ellen;Donovan, Molly;Meng, Yan;Grant, George;Mash, Deborah;Marcus, Yvonne;Basile, Margaret;Liu, Jun;Zhu, Jun;Tu, Zhidong;Cox, Nancy J.;Nicolae, Dan L.;Gamazon, Eric R.;Im, Hae Kyung;Konkashbaev, Anuar;Pritchard, Jonathan;Stevens, Matthew;Flutre, Timothee;Wen, Xiaoquan;Dermitzakis, Emmanouil T.;Lappalainen, Tuuli;Guigo, Roderic;Monlong, Jean;Sammeth, Michael;Koller, Daphne;Battle, Alexis;Mostafavi, Sara;McCarthy, Mark;Rivas, Manual;Maller, Julian;Rusyn, Ivan;Nobel, Andrew;Wright, Fred;Shabalin, Andrey;Feolo, Mike;Sharopova, Nataliya;Sturcke, Anne;Paschal, Justin;Anderson, James M.;Wilder, Elizabeth L.;Derr, Leslie K.;Green, Eric D.;Struewing, Jeffery P.;Temple, Gary;Volpi, Simona;Boyer, Joy T.;Thomson, Elizabeth J.;Guyer, Mark S.;Cathy Ng;Abdallah, Assya;Colantuoni, Deborah;Insel, Thomas R.;Koester, Susan E.;Little, A. Roger;Bender, Patrick K.;Lehner, Thomas;Yao, Yin;Compton, Carolyn C.;Vaught, Jimmie B.;Sawyer, Sherilyn;Lockhart, Nicole C.;Demchok, Joanne;Moore, Helen F.
通讯作者：
Moore, Helen F.