Clinical significance on the detection of serum methylated tissue factor pathway inhibitor 2 gene in the diagnosis of gastric cancer

doi:10.3969/j.issn.1673-8640.2014.07.005

Abstract

Abstract:

Objective　Through the detection of serum and tissue methylated tissue factor pathway inhibitor 2（TFPI-2） gene， to investigate its clinical significance as a tumor marker for the diagnosis of gastric cancer. Methods　A total of 32 gastric cancer patients and 29 atrophic gastritis patients were enrolled， and 32 healthy subjects including superficial gastritis were enrolled as control group. Methylated TFPI-2 gene was detected by methylation-specific polymerase chain reaction（MSP）. Carcinoembryonic antigen（CEA） and carbohydrate antigen 199（CA199） were determined by electrochemiluminescence immunoassay. Results　The positive rates of methylated TFPI-2 gene in tissue were 53.13% in gastric cancer group， 37.93% in atrophic gastritis group and 3.33% in control group. Tissue methylated TFPI-2 gene was significantly higher in gastric cancer group than in control group（P＜0.05）. The positive rates of methylated TFPI-2 gene in serum were 28.13% in gastric cancer group， 6.90% in atrophic gastritis group， but none in control group. Serum methylated TFPI-2 gene was significantly higher in gastric cancer group than in atrophic gastritis group（P＜0.05） and in control group（P＜0.05）. The sensitivity and specificity of serum methylated TFPI-2 gene for the diagnosis of gastric cancer were 28.13% and 96.61%. The 37.93% positive rate was got in serum against tissue. The TFPI-2 gene methylation in serum showed no correlation with sex， age， Borrmann′ s classification， CEA and CA199 in gastric cancer group（P＞0.05）. In gastric cancer group， the positive rates of methylated TFPI-2 gene， CEA and CA199 were 28.13%， 21.88% and 18.75%， respectively. If performing the combined determination of all the 3 parameters， the positive rate was 53.13%， and the positive rate was significantly higher than those of the single determinations（P＜0.05）. Conclusions　The TFPI-2 gene methylation in serum derives from gastric cancer tissues， and it shows high specificity for the diagnosis of gastric cancer， but the sensitivity is relatively low. It can improve the sensitivity if performing the combined determination with CEA and CA199. The detection of serum TFPI-2 gene methylation has certain significance for diagnosing gastric cancer.

Key words: Tissue factor pathway inhibitor 2 gene, Methylation, Serum free DNA, Gastric cancer

CLC Number:

R446.11

ZHU Liyue,GUAN Ming,KANG Zhihua,GAO Jianping,WENG Lizhen,ZHANG Li,HU Leiguang. Clinical significance on the detection of serum methylated tissue factor pathway inhibitor 2 gene in the diagnosis of gastric cancer[J]. , 2014, 29(7): 712-717.

References

[1] Zou HZ, Yu BM, Wang ZW, et al. Detection of aberrant p16 methylation in the serum of colorectal cancer patients[J]. Clin Cancer Res, 2002, 8(1): 188-191.
[2] Monk D, Wagschal A, Arnaud P, et al. Comparative analysis of human chromosome 7q21 and mouse proximal chromosome 6 reveals a placental-specific imprinted gene, TFPI2/Tfpi2, which requires EHMT2 and EED for allelic-silencing[J]. Genome Res, 2008, 18(8):1270-1281.
[3] Khan S, Coulson JM, Woll PJ. Genetic abnormalities in plasma DNA of patients with lung cancer and other respiratory diseases[J]. Int J Cancer, 2004, 110(6): 891-895.
[4] Jee CD, Kim MA, Jung EJ, et al. Identification of genes epigenetically silenced by CpG methylation in human gastric carcinoma[J]. Eur J Cancer, 2009, 45(7): 1282-1293.
[5] Takada H, Wakabayashi N, Dohi O, et al. Tissue factor pathway inhibitor 2 (TFPI2) is frequently silenced by aberrant promoter hypermethylation in gastric cancer[J]. Cancer Genet Cytogenet, 2010, 197(1): 16-24.
[6] Hibi K, Goto T, Kitamura YH, et al. Methylation of the TFPI2 gene is frequently detected in advanced gastric carcinoma[J]. Anticancer Res, 2010, 30(10): 4131-4133.
[7] Glckner SC, Dhir M, Yi J M, et al. Methylation of TFPI2 in stool DNA: a potential novel biomarker for the detection of colorectal cancer[J]. Cancer Res, 2009, 69(11): 4691-4699.
[8] Qu Y, Dang S, Hou P. Gene methylation in gastric cancer[J]. Clin Chim Acta, 2013, 424:53-65.
[9] Kong D, Ma D, Bai H, et al. Expression and characterization of the first kunitz domain of human tissue factor pathway inhibitor-2[J]. Biochem Biophys Res Commun, 2004, 324(4): 1179-1185.
[10] Takada H, Wakabayashi N, Dohi O, et al. Tissue factor pathway inhibitor 2 (TFPI2) is frequently silenced by aberrant promoter hypermethylation in gastric cancer[J]. Cancer Genet Cytogenet, 2010, 197(1): 16-24.
[11] 冷雪,孙保存,臧凤琳,等. 胃癌中组织因子途径抑制剂2的表达及其与预后和肿瘤血管生成模式的相关性研究[J]. 中国肿瘤临床, 2012, 39(8):433-438.
[12] 马晓杰,李景鹏,赵勇. 血浆中游离核酸: 分子诊断的新靶点[J]. 生命的化学,2006,26(2): 147-149.
[13] 胡影,倪虹. 人体游离循环 DNA 的研究进展[J]. 遗传,2008,30(7): 815-820.
[14] 孙振阳,汤志刚. TFPI-2基因与消化道肿瘤关系的研究进展[J]. 中华肿瘤防治杂志,2008,15(3): 227-230.
[15] 陆俊骏,钱烨,连强.胃癌遗传学及表遗传学研究进展[J]. 中国医药导报,2013,10(19):43-46.
[16] Lo Nigro C, Wang H, McHugh A, et al. Methylated tissue factor pathway inhibitor 2 (TFPI2) DNA in serum is a biomarker of metastatic melanoma[J]. J Invest Dermatol, 2013, 133(5): 1278-1285.

[1]	GAO Feng. Clinical application of novel tumor biomarkers：prospects and challenges [J]. Laboratory Medicine, 2023, 38(4): 303-306.
[2]	LIU Ruili, LI Lanjun, JIA Minlei, WANG Yihui, HAO Weina. Correlation between tumor miR-7-5p and NOVA2 levels and clinical prognosis in cancer tissues of patients with gastric cancer [J]. Laboratory Medicine, 2023, 38(4): 325-329.
[3]	GUO Shuang, LIU Hongli, LI Ya. Progression of migration and invasion-related miRNA and lncRNA in Epstein-Barr virus-associated gastric cancer [J]. Laboratory Medicine, 2023, 38(10): 987-996.
[4]	WANG Rui, LI Zhaoyan, ZHAO Aiguang. Application of circulating tumor DNA detection in the diagnosis and treatment of gastric cancer [J]. Laboratory Medicine, 2022, 37(9): 877-881.
[5]	NIE Tian, RAN Zihan, JIN Lei. Research progress on the relationship between interleukin gene polymorphisms and gastric cancer [J]. Laboratory Medicine, 2022, 37(9): 882-886.
[6]	JI Ye, YUAN Xiaosun, ZHANG Lei, MA Huili, DONG Wei, LI Changsheng, ZHANG Jingwei, REN Zhonghai, ZHANG Yifei. Expression level of lncRNA SNHG15 in gastric cancer and clinical significance [J]. Laboratory Medicine, 2022, 37(5): 409-412.
[7]	LIANG Chunfang, ZHU Kangning, ZHANG Qi. Serum miR-21 and miR-135a expression levels in predicting the recurrence and metastasis of gastric cancer patients after chemotherapy [J]. Laboratory Medicine, 2022, 37(5): 417-422.
[8]	GONG Zhiyun, JIANG Minglei, SHI Weizhong, LU Renquan, GUO Lin. Application value of fecal SDC2 gene methylation determination in the auxiliary diagnosis of colorectal cancer [J]. Laboratory Medicine, 2022, 37(4): 325-329.
[9]	LIU Kai, ZHANG Peiru, XIE Suhong, GUO Lin, LU Renquan. Clinical value of the SorCS1 gene promoter methylation determination in patients with colorectal cancer [J]. Laboratory Medicine, 2022, 37(4): 330-335.
[10]	MAO Zheng, QIAN Zengkun, YING Fei, WANG Zhaoli, XIAO Qun, CUI Fan. Correlation between E-Cad,G-17,HER-2 and postoperative recurrence risk of gastric cancer [J]. Laboratory Medicine, 2022, 37(1): 41-46.
[11]	XIONG Zhongbo, WANG Lei, YIN Beiqi, DAI Yue, WEI Xiaoqing, LU Pei. Clinical roles of SAA and CRP in pathological staging and metastasis of gastrointestinal cancer [J]. Laboratory Medicine, 2022, 37(1): 51-55.
[12]	SHI Yue, DONG Dong. Research progress of circulating tumor DNA in renal cell carcinoma [J]. Laboratory Medicine, 2020, 35(9): 952-956.
[13]	HANG Chen, HUANG Biao, PENG Haixia, WEI Xin, XU Weihong, SHENG Huiming, LI Ningli. Role of TRFIA for detecting pepsinogen in screening ulcer gastric cancer [J]. Laboratory Medicine, 2020, 35(7): 721-725.
[14]	JIN Shu, ZHU Qi, ZHU Yuan, YUAN Ya, CAI Xiaoyao, ZHANG Ji, YAN Peiyi. Methylation level and mRNA expression of CpG island of HER2 gene in breast cancer and its adjacent tissues [J]. Laboratory Medicine, 2020, 35(5): 481-486.
[15]	ZHOU Fengli, CHU Yimin, LI Ji, YANG Daming, PENG Haixia, XU Ying. LncRNA SNHG1 promoting the growth of gastric cancer through binding to miR-145 [J]. Laboratory Medicine, 2020, 35(10): 1062-1069.