Novel Biomarkers for Prostate Cancer Including Noncoding Transcripts

Novel Biomarkers for Prostate Cancer Including Noncoding Transcripts
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DOI:
10.2353/ajpath.2009.080868
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发表时间:
2009-12-01
影响因子:
6
通讯作者:
Sadar, Marianne D.
Sadar, Marianne D.
中科院分区:
医学2区
文献类型:
--
作者:
Romanuik, Tammy L.;Ueda, Takeshi;Sadar, Marianne D.

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研究了 27 种转录本的水平作为前列腺癌的潜在新标志物,包括编码质膜蛋白的基因(ADAM2、ELOVL5、MARCKSL1、RAMP1、TMEM30A 和 TMEM66);分泌蛋白(SPON2、TMEM30A、TMEM66 和截短的 TMEFF2(称为 POP4));细胞内蛋白(CAMK2N1、DHCP24、GLO1、NGFP-4P1、PGK1、PSMA 7、SBDS 和 YWMQ);和非编码转录本(来自 mRNA AK000023 的 POP1(100 kb))、POP2(来自 mRNA AL832227 的 4 kb)、POP3(来自 FSF CF140309 的 50 kb)、POP5(NGAM2 的内含子,登录号 DO668384)、POP6(FHIT 的内含子、POP`7(TNFAIP8 的内含子)、 POP8(EFNA5 的内含子)、POP9(DSTN 的内含子)、POP10(ADAM2 的内含子,登录号 DO668396)、POP11(来自 EST BG194644 的 87kb)和 POP12(EST BQ226050 的内含子)。 POP3 的表达具有前列腺特异性,而 ADAM2、POP1、POP4、POP10、ELOVL5、RAMP1 和 SPON2 的组织表达有限。 ELOVL5、MARCKSL1、NGFRAP1、PGK1、POP2、POP5、POP8、PSMA 7、RAMP1 和 SPON2 在激光显微切割的前列腺组织恶性与良性临床样本之间表达显着差异。 PGK1、POP2 和 POP12 与临床参数相关。在后来生化失败的原发性前列腺癌患者中,CAMK2N1、GLO1、SDBS 和 TMEM30A 转录物的水平往往会升高。与雄激素依赖性原发性前列腺癌相比,转移性去势复发性疾病中 GLO1、DHCR24、NGFRAP1、KLK3 和 RAMP1 的表达显着降低。因此,这些新的潜在生物标志物可能有助于前列腺癌的诊断/预后。 (Am J Pathol 2009, 175.,2264 -2276; DOI: 10.2353/ajpath.2009.080868)
Levels of 27 transcripts were investigated as potential novel markers for prostate cancer, including genes encoding plasma membrane proteins (ADAM2, ELOVL5, MARCKSL1, RAMP1, TMEM30A, and TMEM66); secreted proteins (SPON2, TMEM30A, TMEM66, and truncated TMEFF2 (called POP4)); intracelhilar proteins (CAMK2N1, DHCP24, GLO1, NGFP-4P1, PGK1, PSMA 7, SBDS, and YWMQ); and noncoding transcripts (POP1 (100 kb) from mRNA AK000023), POP2 (4 kb from mRNA AL832227), POP3 (50 kb from FSF CF140309), POP5 (intron of NGAM2, accession DO668384), POP6 (intron of FHIT, POP`7 (intron of TNFAIP8), POP8 (intron of EFNA5), POP9 (intron of DSTN), POP10 (intron of ADAM2, accession DO668396), POP11 (87kb from EST BG194644), and POP12 (intron of EST BQ226050)). Expression of POP3 was prostate specific, whereas ADAM2, POP1, POP4, POP10, ELOVL5, RAMP1, and SPON2 had limited tissue expression. ELOVL5, MARCKSL1, NGFRAP1, PGK1, POP2, POP5, POP8, PSMA 7, RAMP1, and SPON2 were significantly differentially expressed between laser microdissected malignant versus benign clinical samples of prostate tissue. PGK1, POP2, and POP12 correlated to clinical parameters. Levels of CAMK2N1, GLO1, SDBS, and TMEM30A transcripts tended to be increased in primary prostate cancer from patients who later had biochemical failure. Expression of GLO1, DHCR24, NGFRAP1, KLK3, and RAMP1 were significantly decreased in metastatic castration-recurrent disease compared with androgen-dependent primary prostate cancer. These novel potential biomarkers may therefore be useful in the diagnosis/prognosis of prostate cancer. (Am J Pathol 2009, 175.,2264 -2276; DOI: 10.2353/ajpath.2009.080868)