血浆多基因甲基化检测对结直肠癌的早期诊断效能分析

盛宁宁; 郭毅; 侯先存; 王怡裕; 徐银海

doi:10.12182/20251160604

血浆多基因甲基化检测对结直肠癌的早期诊断效能分析

Performance of Plasma Multigene Methylation Testing in Early Diagnosis of Colorectal Cancer

摘要

摘要:
目的探讨基于血浆多基因甲基化检测构建的诊断模型在结直肠癌（colorectal cancer, CRC）诊断中的效能。
方法纳入2022年7月–2024年6月在徐州医科大学附属医院接受检查的可疑CRC患者688例，术前检测其血浆隔膜蛋白9（SEPTIN9）、支链氨基酸转氨酶1（branched chain amino acid transaminase 1, BCAT1）、IKAROS家族锌指1（IKAROS family zinc finger 1, IKZF1）、短软骨素（brevican, BCAN）、Vav3鸟嘌呤核苷酸交换因子（vav guanine nucleotide exchange factor 3, VAV3）基因的甲基化状态。将上述5种基因甲基化检测结果与其病理结果进行比较，构建基于SEPTIN9、BCAT1、IKZF1、BCAN、VAV3基因甲基化的诊断模型，并评估其对CRC的诊断效能。
结果 688例患者中，48例病理确诊为CRC。单基因甲基化检测诊断CRC的效能如下：SEPTIN9灵敏度为47.92%，特异度96.72%，预测曲线下面积（area under the curve, AUC）为0.804〔95%可信区间（confidence interval, CI）：0.672～0.899）〕；BCAT1灵敏度52.08%，特异度96.88%，预测AUC为0.753（95%CI：0.702～0.864）；IKZF1灵敏度50.00%，特异度98.28%，预测AUC为0.740（95%CI：0.635～0.881）；BCAN灵敏度33.33%，特异度98.75%，预测AUC为0.690（95%CI：0.572～0.785）；VAV3灵敏度为35.42%，特异度97.66%，预测AUC为0.686（95%CI：0.597～0.734）。整合5种基因构建的诊断模型灵敏度为85.42%，特异度93.40%，预测AUC为0.916（95%CI：0.835～0.972）。该模型对不同CRC分期的诊断灵敏度分别为：Ⅰ期85.71%、Ⅱ期92.86%、Ⅲ期78.95%、分期不明87.50%。
结论基于血浆SEPTIN9、BCAN、IKZF1、BCAT1、 VAV3基因甲基化水平构建的诊断模型具有良好的CRC诊断效能，特别是针对早期CRC。

Abstract:
Objective To explore the performance of a predictive model based on plasma multigene methylation testing in the early diagnosis of colorectal cancer (CRC).
Methods A total of 688 patients with suspected CRC who underwent diagnostic examination at the Affiliated Hospital of Xuzhou Medical University between July 2022 and June 2024 were enrolled. The plasma methylation status of 5 genes, including SEPTIN9 (septin 9), BCAT1 (branched chain amino acid transaminase 1), IKZF1 (IKAROS family zinc finger 1), BCAN (brevican), and VAV3 (vav guanine nucleotide exchange factor 3), was assessed before pathological biopsy. The negative or positive results of the methylation testing of the 5 genes were compared with the clinical pathological diagnosis results of the same participants to construct a predictive model based on the methylation status of SEPTIN9, BCAT1, IKZF1, BCAN, and VAV3 genes, and the performance of the predictive model in the early diagnosis of CRC patients was evaluated.
Results Of the 688 patients, 48 had a pathologically confirmed diagnosis of colorectal carcinoma. The diagnostic performance of a single-gene methylation status for CRC was as follows: SEPTIN9 showed a sensitivity of 47.92%, specificity of 96.72%, and AUC of 0.804 (95% CI: 0.672-0.899); BCAT1 showed a sensitivity of 52.08%, specificity of 96.88%, and AUC of 0.753 (95% CI: 0.702-0.864); IKZF1 showed a sensitivity of 50.00%, specificity of 98.28%, and AUC of 0.740 (95% CI: 0.635-0.881); BCAN showed a sensitivity of 33.33%, specificity of 98.75%, and AUC of 0.690 (95% CI: 0.572-0.785); VAV3 showed a sensitivity of 35.42%, specificity of 97.66%, and AUC of 0.686 (95% CI: 0.597-0.734). A diagnostic model integrating the 5 genes achieved a sensitivity of 85.42%, specificity of 93.40%, and AUC of 0.916 (95% CI: 0.835-0.972). The diagnostic sensitivities of the model for CRC of different stages were 85.71% for stage Ⅰ, 92.86% for stage Ⅱ, 78.95% for stage Ⅲ, and 87.50% for unstaged cases.
Conclusion A diagnostic model based on the methylation levels of the SEPTIN9, BCAT1, IKZF1, BCAN, and VAV3 genes in plasma demonstrates good diagnostic performance for CRC, particularly in early-stage cases.

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