Value of combined detection of SFRP2 and SDC2 methylation in fecal samples for colorectal cancer screening and prognostic assessment
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摘要:
目的 探究粪便中SFRP2和SDC2基因甲基化联合检测在结直肠癌(CRC)筛查、诊断及预后评估中的临床价值，为无创筛查和个体化治疗提供依据。 方法 纳入2019年1—12月在蚌埠医科大学第一附属医院接受结肠镜检查的323例受试者，根据检查结果分为CRC组(149例)、腺瘤组(60例)、健康组(114例)。采用实时荧光定量PCR技术检测受试者粪便样本中SFRP2和SDC2基因的甲基化水平。使用χ2检验分析不同患者临床病理特征CRC患者甲基化状态差异；采用Kaplan-Meier法比较生存差异；运用Cox回归模型分析影响预后的独立危险因素。 结果 CRC组SFRP2、SDC2甲基化阳性率均显著高于腺瘤组和健康组(P < 0.001)，且联合检测结果显示CRC组阳性检出率为91.95%(137/149)，不同分化程度及TNM分期结直肠癌患者SFRP2和SDC2基因甲基化阳性率差异均有统计学意义(P＜0.001)。生存分析显示，SFRP2(log-rank χ2=14.300)、SDC2(log-rank χ2=23.240)甲基化阳性患者总生存率更低(P < 0.001)。Cox多因素分析结果显示，分化程度、TNM分期及SFRP2、SDC2甲基化可能是结直肠癌预后的独立影响因素(P < 0.05)。 结论 粪便中联合检测SFRP2和SDC2基因甲基化可提高结直肠癌检出率，其水平与肿瘤分化、TNM分期及生存率相关，这对早期筛查和个体化治疗具有重要的临床价值。 Abstract:Objective To investigate the clinical value of combined detection of SFRP2 and SDC2 gene methylation in faeces for the screening, diagnosis and prognostic assessment of colorectal cancer (CRC), providing a molecular basis for non-invasive screening and individualized treatment. Methods A total of 323 subjects who underwent colonoscopy at the First Affiliated Hospital of Bengbu Medical University between January 2019 and December 2019 were enrolled in the study. The subjects were categorized based on pathological diagnosis, they were divided into the CRC group (n=149), the adenoma group (n=60), and the healthy control group (n=114). The methylation levels of the SFRP2 and SDC2 genes in faecal samples were detected using quantitative real-time PCR (qRT-PCR). The χ2 test was utilized to analyze the differences in methylation status among the clinical and pathological characteristics of different patients with CRC. The survival differences between the two groups were then compared using the Kaplan-Meier method. Cox regression models were utilized in order to analyze the independent risk factors affecting prognosis. Results The methylation-positive rates of both SFRP2 and SDC2 in the CRC group were significantly higher than those in the adenoma and healthy control groups (P < 0.001). The application of combined detection techniques resulted in a positive detection rate of 91.95% (137/149) within the CRC group. Statistically significant differences were identified in the positive rates of SFRP2 and SDC2 gene methylation among patients with different degrees of differentiation and different TNM stages of colorectal cancer (P < 0.001). Survival analysis revealed that patients positive for SFRP2 methylation (log-rank χ2=14.300) and SDC2 methylation (log-rank χ2=23.240) exhibited significantly lower overall survival rates (P < 0.001). Cox multivariate analysis identified differentiation degree, TNM stage, and SFRP2 / SDC2 methylation as independent risk factors affecting CRC prognosis (P < 0.05). Conclusion The combined detection of SFRP2 and SDC2 gene methylation in faeces has been demonstrated to enhance the detection rate of CRC. Their levels correlate with tumor differentiation, TNM stage and survival rate, which provides important clinical value for early screening and individualized treatment. -
Key words:
- Colorectal cancer /
- SFRP2 /
- SDC2 /
- Prognosis
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图 1 不同SFRP2和SDC2表达状态结直肠癌患者的生存曲线
Figure 1. Kaplan-Meier survival curves for colorectal cancer patients stratified by combined SFRP2 and SDC2 expression status
表 1 3组受试者基线资料比较(例)
Table 1. Comparison of baseline data among the three groups of subjects (cases)
组别 例数 性别 年龄 男性 女性 ＜60岁 ≥60岁 CRC组 149 89 60 94 55 腺瘤组 60 40 20 35 25 健康组 114 70 44 68 46 χ2值 0.873 0.540 P值 0.646 0.764 
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表 2 3组受试者粪便SFRP2和SDC2基因甲基化阳性检出率比较[例(%)]
Table 2. Comparison of positive detection rates of SFRP2 and SDC2 gene methylation in stool samples among the three groups [cases (%)]
组别 例数 SFRP2 SDC2 联合检测 CRC组 149 104(69.80)ab 97(65.10)ab 137(91.95)ab 腺瘤组 60 15(25.00) 21(35.00) 34(56.67) 健康组 114 0 0 0 χ2值 139.666 118.127 219.575 P值 ＜0.001 ＜0.001 ＜0.001 注：与腺瘤组比较，aP＜0.001；与健康组比较，bP＜0.001。
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表 3 不同临床病理特征结直肠癌患者SFRP2及SDC2甲基化阳性率比较(例)
Table 3. Comparison of positive detection rates of SFRP2 and SDC2 methylation by clinicopathological characteristics in colorectal cancer patients (cases)
项目 例数 SFRP2 χ2值 P值 SDC2 χ2值 P值 阳性 阴性 阳性 阴性 性别 1.097 0.295 < 0.001 0.983 男性 89 65 24 58 31 女性 60 39 21 39 21 年龄(岁) 0.780 0.377 0.005 0.945 ＜60 55 36 19 36 19 ≥60 94 68 26 61 33 分化程度 17.659 ＜0.001 17.179 ＜0.001 高分化 91 75 16 71 20 中低分化 58 29 29 26 32 TNM分期 30.890 ＜0.001 17.688 ＜0.001 Ⅰ~Ⅱ 71 34 37 34 37 Ⅲ 78 70 8 63 15
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表 4 结直肠癌患者预后影响因素的单因素Cox回归分析
Table 4. Univariate Cox regression analysis of prognostic factors in colorectal cancer patients
变量 B SE Waldχ2 HR值 95% CI P值 性别(男性) 0.103 0.237 0.190 1.109 0.697~1.765 0.663 年龄(≥60岁) 0.215 0.245 0.767 1.239 0.767~2.003 0.381 分化程度(高分化) 0.755 0.262 8.319 2.127 1.274~3.552 0.004 TNM分期(Ⅲ期) 2.043 0.308 43.875 7.713 4.214~14.118 ＜0.001 SFRP2(阳性) 1.165 0.327 12.693 3.207 1.689~6.008 ＜0.001 SDC2(阳性) 1.446 0.327 19.492 4.245 2.234~8.064 ＜0.001 注：各变量赋值如下，女性=0，男性=1；年龄＜60岁=0，≥60岁=1；分化程度为中低分化=0，高分化=1；TNM分期为Ⅰ~Ⅱ期=0，Ⅲ期=1；甲基化水平阴性=0，阳性=1。
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表 5 结直肠癌患者预后影响因素的多因素Cox回归分析
Table 5. Multivariate Cox regression analysis of prognostic factors in colorectal cancer patients
变量 B SE Waldχ2 HR值 95% CI P值 分化程度(高分化) -1.802 0.386 21.754 0.165 0.077~0.352 ＜0.001 TNM分期(Ⅲ期) 2.792 0.458 37.162 16.315 6.649~40.037 ＜0.001 SFRP2(阳性) 1.087 0.370 8.632 2.964 1.436~6.119 0.003 SDC2(阳性) 1.628 0.348 21.914 5.091 2.576~10.064 ＜0.001
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