结直肠癌患者SorCS1基因启动子甲基化检测的临床价值

doi:10.3969/j.issn.1673-8640.2022.04.006

摘要/Abstract

摘要：

目的探讨结直肠癌患者SorCS1基因启动子甲基化检测的临床价值。方法收集17例结直肠癌患者的癌组织和癌旁组织,采用MassARRAY平台检测结直肠癌患者癌组织与癌旁组织相关基因启动子甲基化水平,筛选出癌组织与癌旁组织基因启动子甲基化存在差异的基因,并与肿瘤基因图谱计划（TCGA）数据库进行比对。同时检测 SEPT9基因甲基化水平。用癌组织基因启动子甲基化检测值与癌旁组织基因启动子甲基化检测值的差值（Δ）表示结直肠癌患者癌组织基因启动子甲基化水平相对于癌旁组织的差异。结果共筛选出2个基因（SorCS1、CASR）。结直肠癌患者癌组织SorCS1、CASR、SEPT9基因启动子甲基化水平均显著高于癌旁组织（P<0.001）。与TCGA数据库的比对结果显示,膀胱尿路上皮癌、宫颈鳞状细胞癌、结肠腺癌、多形性胶质母细胞瘤、直肠腺癌、胃腺癌患者的SorCS1基因相对表达量均低于正常对照者（P<0.05）,结肠癌、直肠癌、肺腺癌患者SorCS1基因启动子甲基化水平明显高于正常对照者（P<0.05）;结直肠癌患者与正常对照者之间CASR基因相对表达量差异无统计学意义（P>0.05）,且TCGA数据库中无CASR基因启动子甲基化的数据。Ⅲ~Ⅳ期、有淋巴结转移的结直肠癌患者ΔSorCS1基因、SEPT9基因启动子甲基化水平分别高于Ⅰ~Ⅱ期患者和无淋巴结转移的患者（P<0.05）,而不同性别、年龄、肿瘤部位、肿瘤直径的患者之间ΔSorCS1基因和SEPT9基因启动子甲基化差异均无统计学意义（P>0.05）;不同临床病理特征结直肠癌患者之间ΔCASR基因甲基化水平差异均无统计学意义（P>0.05）。SorCS1基因甲基化阳性率为82.35%（14/17）,SEPT9基因甲基化阳性率为70.58%（12/17）,两者联合检测的阳性率为88.24%（15/17）。结论结直肠癌患者SorCS1基因启动子甲基化阳性率较高,可与SEPT9基因启动子甲基化检测形成互补,或可作为结直肠癌新的分子标志物。

关键词: SorCS1基因, SEPT9基因, 甲基化, 结直肠癌

Abstract:

Objective To investigate the clinical value of the SorCS1 gene promoter methylation determination in patients with colorectal cancer. Methods Cancer and adjacent tissues from 17 colorectal cancer patients were collected. The MassARRAY platform was used to determine the levels of gene promoter methylation in cancer tissues and adjacent tissues of patients with colorectal cancer,and the genes with different promoter methylation between cancer tissues and adjacent tissues were screened out and then compared with the Cancer Genome Atlasc（TCGA） database. Meanwhile,the methylation levels of SEPT9 gene were determined. The difference （Δ） determined by subtracting the determination value of gene promoter methylation in adjacent tissue from that in cancer tissue indicated the difference. Results A total of 2 genes（SorCS1 and CASR） were screened out. The levels of SorCS1,CASR and SEPT9 methylation in colorectal cancer tissues were higher than those in adjacent cancer tissues（P<0.001）. The comparison with TCGA database revealed that the expressions of SorCS1 gene were lower in patients with bladder urothelial carcinoma,cervical squamous cell carcinoma,colon adenocarcinoma,glioblastoma multiforme,rectum adenocarcinoma and stomach adenocarcinoma than that in healthy controls（P<0.05）,while the promoter methylation level of SorCS1 gene was higher in colon adenocarcinoma,rectum adenocarcinoma and lung adenocarcinoma than that in healthy controls（P<0.05）. The difference of CASR gene expression between colorectal cancer patients and healthy controls was not statistically significant（P>0.05）,and the data of CASR gene promoter methylation was not available in TCGA database. The differences between ΔSorCS1 and SEPT9 gene promoter methylation levels in colorectal cancer patients were associated with tumor stage,and those in progression stage（Ⅲ-Ⅳ） were higher than those in early stage（Ⅰ-Ⅱ）（P<0.05）. The gene promoter methylation differences were also associated with lymph node metastasis,and the higher level of ΔSorCS1 and SEPT9 gene promoter methylation levels appeared in the group of lymph nodes with metastasis than those without metastasis（P<0.05）,independent of sex,age,tumor site and maximum diameter of tumors（P>0.05）. However,there was no statistical significance in ΔCASR between different clinicopathological characteristics of patients（P>0.05）. The positive rate of SorCS1 gene methylation was 82.35%（14/17）,while that of SEPT9 gene methylation was 70.58%（12/17）,respectively. The positive rate of combined determination was 88.24%（15/17）. Conclusions SorCS1 gene promoter methylation determination has a high positive rate in colorectal cancer patients,and it is complementary to SEPT9 gene promoter methylation,which can be a potential new molecular marker for colorectal cancer development.

Key words: SorCS1, SEPT9, Methylation, Colorectal cancer

中图分类号:

R446.7

刘凯, 张沛茹, 谢素红, 郭林, 卢仁泉. 结直肠癌患者SorCS1基因启动子甲基化检测的临床价值[J]. 检验医学, 2022, 37(4): 330-335.

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.

图/表 4

参考文献 24

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组织类型	例数	SEPT9基因启动子甲基化（ΔΔCt）
癌组织	17	5.170（4.015~5.510）
癌旁组织	17	1.210（1.445~2.410）
Z值		-3.243
P值		<0.001

组织类型	例数	SEPT9基因启动子甲基化（ΔΔCt）
癌组织	17	5.170（4.015~5.510）
癌旁组织	17	1.210（1.445~2.410）
Z值		-3.243
P值		<0.001

病理特征	例数	ΔSorCS1基因	ΔCASR基因	SEPT9基因
性别
男性	9	0.330（0.205~0.545）	0.280（0.075~0.440）	31.779（4.509~109.597）
女性	8	0.425（0.253~0.488）	0.245（0.225~0.500）	17.380（4.065~81.032）
U值		30.500	33.500	36.000
P值		0.606	0.810	1.000
年龄
≤60岁	7	0.290（0.150~0.480）	0.280（0.030~0.540）	7.890（1.376~77.708）
>60岁	10	0.445（0.300~0.543）	0.225（0.080~0.415）	39.478（4.650~226.364）
U值		48.500	33.500	24.000
P值		0.193	0.884	0.283
肿瘤分期
Ⅰ~Ⅱ	4	0.205（0.143~0.283）	0.235（0.070~0.355）	2.802（0.401~5.797）
Ⅲ~Ⅳ	13	0.480（0.325~0.520）	0.300（0.070~0.515）	47.177（8.508~116.131）
U值		46.000	21.500	3.000
P值		0.023	0.610	0.009
淋巴结转移
无	8	0.275（0.173~0.443）	0.145（0.008~0.475）	6.340（2.436~41.102）
有	9	0.490（0.360~0.545）	0.380（0.120~0.440）	82.139（25.634~455.087）
U值		56.500	25.000	21.000
P值		0.046	0.290	0.015
病理特征	例数	ΔSorCS1基因	ΔCASR基因	EPT9基因
肿瘤部位
直肠	10	0.400（0.218~0.513）	0.285（0.075~0.550）	8.508（2.612~41.791）
结肠	7	0.400（0.260~0.500）	0.280（0.050~0.380）	69.071（4.509~302.605）
U值		33.500	27.500	10.000
P值		0.887	0.464	0.149
肿瘤直径^①
≤5 cm	12	0.345（0.173~0.498）	0.290（0.045~0.528）	8.508（3.149~75.549）
>5 cm	4	0.390（0.323~0.518）	0.240（0.063~0.388）	64.658（15.387~783.230）
U值		30.000	22.500	14.000
P值		0.521	0.856	0.225

病理特征	例数	ΔSorCS1基因	ΔCASR基因	SEPT9基因
性别
男性	9	0.330（0.205~0.545）	0.280（0.075~0.440）	31.779（4.509~109.597）
女性	8	0.425（0.253~0.488）	0.245（0.225~0.500）	17.380（4.065~81.032）
U值		30.500	33.500	36.000
P值		0.606	0.810	1.000
年龄
≤60岁	7	0.290（0.150~0.480）	0.280（0.030~0.540）	7.890（1.376~77.708）
>60岁	10	0.445（0.300~0.543）	0.225（0.080~0.415）	39.478（4.650~226.364）
U值		48.500	33.500	24.000
P值		0.193	0.884	0.283
肿瘤分期
Ⅰ~Ⅱ	4	0.205（0.143~0.283）	0.235（0.070~0.355）	2.802（0.401~5.797）
Ⅲ~Ⅳ	13	0.480（0.325~0.520）	0.300（0.070~0.515）	47.177（8.508~116.131）
U值		46.000	21.500	3.000
P值		0.023	0.610	0.009
淋巴结转移
无	8	0.275（0.173~0.443）	0.145（0.008~0.475）	6.340（2.436~41.102）
有	9	0.490（0.360~0.545）	0.380（0.120~0.440）	82.139（25.634~455.087）
U值		56.500	25.000	21.000
P值		0.046	0.290	0.015
病理特征	例数	ΔSorCS1基因	ΔCASR基因	EPT9基因
肿瘤部位
直肠	10	0.400（0.218~0.513）	0.285（0.075~0.550）	8.508（2.612~41.791）
结肠	7	0.400（0.260~0.500）	0.280（0.050~0.380）	69.071（4.509~302.605）
U值		33.500	27.500	10.000
P值		0.887	0.464	0.149
肿瘤直径^①
≤5 cm	12	0.345（0.173~0.498）	0.290（0.045~0.528）	8.508（3.149~75.549）
>5 cm	4	0.390（0.323~0.518）	0.240（0.063~0.388）	64.658（15.387~783.230）
U值		30.000	22.500	14.000
P值		0.521	0.856	0.225