Detection of methylated SEPT9 in plasma is a reliable screening method for both left- and right-sided colon cancers.

Detection of methylated SEPT9 in plasma is a reliable screening method for both left- and right-sided colon cancers.
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DOI:
10.1371/journal.pone.0046000
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Molnár B
Molnár B
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Tóth K;Sipos F;Kalmár A;Patai AV;Wichmann B;Stoehr R;Golcher H;Schellerer V;Tulassay Z;Molnár B

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甲基化Septin 9(SEPT 9)是来自外周血的结直肠癌(CRC)的敏感生物标志物。然而,其与癌症定位、基于愈创木脂的粪便潜血试验(gFOBT)和癌胚抗原(CEA)的关系尚未被描述。从结肠镜检查前无疾病证据(NED)(n =92)和手术治疗前CRC(n=92)的患者中采集血浆样本用于SEPT 9分析。   分离DNA并使用Epi proColon试剂盒2.0进行亚硫酸氢盐转化。使用Epi proColon 2.0 RT-PCR测定进行定性测定。从NED(分别为n = 17和27)和CRC(分别为n = 22和27)采集用于gFOBT和CEA分析的样本。    SEPT 9检测在NED和CRC中的阳性率分别为15.2%(14/92)和95.6%(88/92),其中II期至IV期CRC的阳性率为100%(67/67),I期CRC的阳性率为84%(21/25)。在第二次分析中(3次PCR重复中的2次),NED的特异性提高至99%(91/92),CRC中SEPT 9阳性的灵敏度为79.3%(73/92)。NED和CRC中gFOBT阳性率分别为29.4%(5/17)和68.2%(15/22),CEA阳性率分别为14.8%(4/27)和51.8%(14/27)。SEPT 9(84.8%)和CEA(85.2%)的特异性均高于gFOBT(70.6%)。SEPT 9在左半结肠癌(LSCC)和右半结肠癌(RSCC)中的阳性率分别为96.4%(54/56)和94.4%(34/36)。喉鳞状细胞癌和喉鳞状细胞癌gFOBT阳性率分别为83.3%(10/12)和50%(5/10),CEA阳性率分别为60%(9/15)和41.7%(5/12)。血浆中SEPT 9的高度敏感性和特异性使其成为比gFOBT和CEA更好的检测CRC的方法,即使对于更难检测的RSCC。
Methylated Septin 9 (SEPT9) is a sensitive biomarker for colorectal cancer (CRC) from peripheral blood. However, its relationship to cancer localization, guaiac-based fecal occult blood test (gFOBT) and carcinoembryonic antigen (CEA) have not been described. Plasma samples were collected for SEPT9 analysis from patients with no evidence of disease (NED) (n = 92) before colonoscopy and CRC (n = 92) before surgical treatment. DNA was isolated and bisulfite-converted using Epi proColon kit 2.0. Qualitative determination was performed using Epi proColon 2.0 RT-PCR assay. Samples for gFOBT and CEA analysis were collected from NED (n = 17 and 27, respectively) and CRC (n = 22 and 27, respectively). SEPT9 test was positive in 15.2% (14/92) of NED and 95.6% (88/92) of CRC, including 100% (67/67) from stage II to stage IV CRC and 84% (21/25) of stage I CRC when a sample was called positive if 1 out of 3 PCR replicates was positive. In a second analysis (2 out of 3 PCR replicates) specificity improved to 99% (91/92) of NEDs, at a sensitivity of 79.3% (73/92) of SEPT9 positives in CRC. gFOBT was positive in 29.4% (5/17) of NED and 68.2% (15/22) of CRC and elevated CEA levels were detected in 14.8% (4/27) of NED and 51.8% (14/27) of CRC. Both SEPT9 (84.8%) and CEA (85.2%) showed higher specificity than gFOBT (70.6%). SEPT9 was positive in 96.4% (54/56) of left-sided colon cancer (LSCC) cases and 94.4% (34/36) of right-sided colon cancer (RSCC) cases. gFOBT was positive in 83.3% (10/12) of cases with LSCC and 50% (5/10) of cases with RSCC, elevated CEA was detected 60% (9/15) of LSCC and 41.7% (5/12) of RSCC. The high degree of sensitivity and specificity of SEPT9 in plasma makes it a better method to detect CRC than gFOBT and CEA, even for the more difficult to detect RSCC.
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