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LGALS4、CEACAM6、TSPAN8 和 COL1A2:粪便免疫化学检测结果阳性受试者队列中的结直肠癌血液标志物——验证研究。

LGALS4, CEACAM6, TSPAN8, and COL1A2: Blood Markers for Colorectal Cancer-Validation in a Cohort of Subjects With Positive Fecal Immunochemical Test Result.

机构信息

Department of Experimental, Diagnostic and Specialty Medicine, Unit of Histology, Embryology and Applied Biology, University of Bologna, Bologna, Italy.

Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

出版信息

Clin Colorectal Cancer. 2018 Jun;17(2):e217-e228. doi: 10.1016/j.clcc.2017.12.002. Epub 2017 Dec 12.

Abstract

BACKGROUND

A noninvasive blood test for the early detection of colorectal cancer (CRC) is highly required. We evaluated a panel of 4 mRNAs as putative markers of CRC.

MATERIALS AND METHODS

We tested LGALS4, CEACAM6, TSPAN8, and COL1A2, referred to as the CELTiC panel, using quantitative reverse transcription polymerase chain reaction, on subjects with positive fecal immunochemical test (FIT) results and undergoing colonoscopy. Using a nonparametric test and multinomial logistic model, FIT-positive subjects were compared with CRC patients and healthy individuals.

RESULTS

All the genes of the CELTiC panel displayed statistically significant differences between the healthy subjects (n = 67), both low-risk (n = 36) and high-risk/CRC (n = 92) subjects, and those in the negative-colonoscopy, FIT-positive group (n = 36). The multinomial logistic model revealed LGALS4 was the most powerful marker discriminating the 4 groups. When assessing the diagnostic values by analysis of the areas under the receiver operating characteristic curves (AUCs), the CELTiC panel reached an AUC of 0.91 (sensitivity, 79%; specificity, 94%) comparing normal subjects to low-risk subjects, and 0.88 (sensitivity, 75%; specificity, 87%) comparing normal and high-risk/CRC subjects. The comparison between the normal subjects and the negative-colonoscopy, FIT-positive group revealed an AUC of 0.93 (sensitivity, 82%; specificity, 97%).

CONCLUSION

The CELTiC panel could represent a useful tool for discriminating subjects with positive FIT findings and for the early detection of precancerous adenomatous lesions and CRC.

摘要

背景

人们强烈需要一种非侵入性的血液检测方法来早期发现结直肠癌(CRC)。我们评估了一组 4 个 mRNA,将其作为 CRC 的潜在标志物。

材料和方法

我们使用定量逆转录聚合酶链反应(qRT-PCR)检测 LGALS4、CEACAM6、TSPAN8 和 COL1A2,简称 CELTiC 面板,用于检测粪便免疫化学检测(FIT)阳性结果并接受结肠镜检查的受试者。使用非参数检验和多项逻辑回归模型,将 FIT 阳性受试者与 CRC 患者和健康个体进行比较。

结果

CELTiC 面板的所有基因在健康受试者(n=67)、低风险受试者(n=36)和高风险/CRC 受试者(n=92)以及阴性结肠镜检查、FIT 阳性组(n=36)之间均显示出统计学显著差异。多项逻辑回归模型显示 LGALS4 是区分 4 组的最有力标志物。通过分析接收者操作特征曲线(ROC)下的面积(AUC)评估诊断价值,CELTiC 面板在将正常受试者与低风险受试者进行比较时,AUC 为 0.91(灵敏度为 79%,特异性为 94%),在将正常和高风险/CRC 受试者进行比较时,AUC 为 0.88(灵敏度为 75%,特异性为 87%)。将正常受试者与阴性结肠镜检查、FIT 阳性组进行比较时,AUC 为 0.93(灵敏度为 82%,特异性为 97%)。

结论

CELTiC 面板可作为区分 FIT 阳性发现受试者的有用工具,并可早期发现癌前腺瘤性病变和 CRC。

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