Zhang Xie, Song Yu-Fei, Lu Hong-Na, Wang Dan-Ping, Zhang Xue-Song, Huang Shi-Liang, Sun Bei-Lei, Huang Zhi-Gang
Xie Zhang, Yu-Fei Song, Hong-Na Lu, Xue-Song Zhang, Shi-Liang Huang, Bei-Lei Sun, Department of Gastroenterology, Ningbo Medical Treatment Center Li Huili Hospital, Ningbo 315040, Zhejiang Province, China.
World J Gastroenterol. 2015 Mar 7;21(9):2629-37. doi: 10.3748/wjg.v21.i9.2629.
To investigate GATA5, SFRP2, and ITGA4 methylation in plasma DNA as noninvasive biomarkers for colorectal cancer (CRC) or adenomas.
There were 57 CRC patients, 30 adenomas patients, and 47 control patients enrolled in this study. Methylation-specific polymerase chain reaction was used to determine the promoter methylation status of GATA5, SFRP2, and ITGA4 genes in plasma DNA, and their association with clinical outcome in CRC. The predictive ability of GATA5, SFRP2, and ITGA4 methylation, individually or in combination, to detect CRC or adenomas was further analyzed.
Hypermethylated GATA5 was detected in plasma in 61.4% (35/57) of CRC cases, 43.33% (13/30) of adenoma cases, and 21.28% (10/47) of control cases. The hypermethylation of SFRP2 was detected in 54.39% (31/57), 40.00% (12/30), and 27.66% (13/47) in plasma samples from CRC, adenomas, and controls, respectively. ITGA4 methylation was detected in 36.84% (21/57) of plasma samples of CRC patients and in 30.00% (9/30) of plasma samples from patients with colorectal adenomas, and the specificity of this individual biomarker was 80.85% (9/47). Moreover, GATA5 methylation in the plasma was significantly correlated with larger tumor size (P = 0.019), differentiation status (P = 0.038), TNM stage (P = 0.008), and lymph node metastasis (P = 0.008). SFRP2 and ITGA4 methylation in plasma significantly correlated with differentiation status (SFRP2, P = 0.012; ITGA4, P = 0.007), TNM stage (SFRP2, P = 0.034; ITGA4, P = 0.021), and lymph node metastasis (SFRP2, P = 0.034; ITGA4, P = 0.021). From the perspective of predictive power and cost-performance, using GATA5 and SFRP2 together as methylation markers seemed the most favorable predictor for CRC (OR = 8.06; 95%CI: 2.54-25.5; P < 0.01) and adenomas (OR = 3.35; 95%CI: 1.29-8.71; P = 0.012).
A combination of GATA5 and SFRP2 methylation could be promising as a marker for the detection and diagnosis of CRC and adenomas.
研究血浆DNA中GATA5、SFRP2和ITGA4甲基化作为结直肠癌（CRC）或腺瘤的非侵入性生物标志物。
本研究纳入57例CRC患者、30例腺瘤患者和47例对照患者。采用甲基化特异性聚合酶链反应检测血浆DNA中GATA5、SFRP2和ITGA4基因的启动子甲基化状态及其与CRC临床结局的关系。进一步分析GATA5、SFRP2和ITGA4甲基化单独或联合检测CRC或腺瘤的预测能力。
CRC病例中61.4%（35/57）、腺瘤病例中43.33%（13/30）和对照病例中21.28%（10/47）的血浆中检测到GATA5高甲基化。CRC、腺瘤和对照血浆样本中SFRP2高甲基化的检出率分别为54.39%（31/57）、40.00%（12/30）和27.66%（13/47）。CRC患者血浆样本中36.84%（21/57）和结直肠腺瘤患者血浆样本中30.00%（9/30）检测到ITGA4甲基化，该单一生物标志物的特异性为80.85%（9/47）。此外，血浆中GATA5甲基化与肿瘤较大尺寸（P = 0.019）、分化状态（P = 0.038）、TNM分期（P = 0.008）和淋巴结转移（P = 0.008）显著相关。血浆中SFRP2和ITGA4甲基化与分化状态（SFRP2，P = 0.012；ITGA4，P = 0.007）、TNM分期（SFRP2，P = 0.034；ITGA4，P = 0.021）和淋巴结转移（SFRP2，P = 0.034；ITGA4，P = 0.021）显著相关。从预测能力和性价比来看，联合使用GATA5和SFRP2作为甲基化标志物似乎是CRC（OR = 8.06；95%CI：2.54 - 25.5；P < 0.01）和腺瘤（OR = 3.35；95%CI：1.29 - 8.71；P = 0.012）最有利的预测指标。
GATA5和SFRP2甲基化联合检测有望成为CRC和腺瘤检测与诊断的标志物。
