Background & Aims

An algorithm based on fecal levels of 2 microRNAs (miR-421 and miR-27a-3p), fecal hemoglobin concentration, and patient age and sex can identify patients with advanced colorectal neoplasia. We investigated whether this algorithm, called miRFec, could increase effectiveness and efficiency of fecal immunochemical test (FIT)-based colorectal cancer (CRC) screening programs.

Methods

We obtained data and fecal samples from 767 persons with a positive result from the FIT who then underwent colonoscopy examination while participating a population-based CRC screening program, from March 2011 through May 2017 in Barcelona, Spain. Fecal miRNAs were isolated from the buffer contained in the original FIT collection device and analyzed by quantitative reverse transcription PCR. Aims were to evaluate the usefulness of the miRFec algorithm in identifying persons at greatest risk for CRC who should be prioritized for colonoscopy examination and individuals at low risk for whom colonoscopy could be avoided.

Results

Of the 767 study subjects, 414 (54.0%) were found by colonoscopy to have advanced colorectal neoplasia (67 with CRC and 347 with advanced adenomas) and 353 (46.0%) were found to have either non-advanced adenomas (n = 136) or a normal examination (n = 217). MiRFec algorithm scores (1–4) were independently associated with the presence of advanced colorectal neoplasia (P < .001). The miRFec algorithm differentiated patients with CRC from those with non-advanced adenomas or normal colonoscopy with an area under the receiver operating characteristic curve of 90% (95% CI, 86–94). Subjects with miRFec scores in the 4th quartile (above 3.09, high-risk group) were 8-fold more likely to have advanced colorectal neoplasia than subjects with miRFec scores in the 1st quartile (below 2.14, low-risk group). Subjects in the low-risk group had a positive predictive value below 30% for detection of advanced colorectal neoplasia. When we used a 50% specificity cut-off value, the miRFec algorithm identified 97% of patients with CRC and would allow 264 subjects (34.4%) to avoid colonoscopy examination.

Conclusions

An algorithm based on fecal levels of 2 miRNAs and hemoglobin, patient age and sex (miRFec) differentiated patients with CRC from those with non-advanced adenomas or normal colonoscopy with an area under the receiver operating characteristic curve value of 90% and avoided 34% of colonoscopies. Inclusion of this algorithm in FIT-based CRC screening programs could increase their effectiveness and efficiency.

中文翻译：

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基于粪便 MicroRNA 的算法提高了基于粪便免疫化学测试的结直肠癌筛查的有效性。

背景与目标

基于 2 个 microRNA（miR-421 和 miR-27a-3p）的粪便水平、粪便血红蛋白浓度以及患者年龄和性别的算法可以识别晚期结直肠肿瘤患者。我们研究了这种称为 miRFec 的算法是否可以提高基于粪便免疫化学测试 (FIT) 的结直肠癌 (CRC) 筛查项目的有效性和效率。

方法

我们从 2011 年 3 月至 2017 年 5 月在西班牙巴塞罗那参加基于人群的 CRC 筛查计划时，从 767 名 FIT 结果呈阳性的人中获得了数据和粪便样本，这些人随后接受了结肠镜检查。从包含在原始 FIT 收集装置中的缓冲液中分离粪便 miRNA，并通过定量逆转录 PCR 进行分析。目的是评估 mirFec 算法在识别 CRC 风险最高且应优先进行结肠镜检查的人群和可避免结肠镜检查的低风险人群方面的有用性。

结果

在 767 名研究对象中，通过结肠镜检查发现 414 名（54.0%）患有晚期结直肠肿瘤（67 名患有 CRC，347 名患有晚期腺瘤），353 名（46.0%）被发现患有非晚期腺瘤（n = 136）或正常检查（n = 217）。MiRFec 算法评分 (1-4) 与晚期结直肠肿瘤的存在独立相关 (P < .001)。MiRFec 算法将 CRC 患者与非晚期腺瘤患者或结肠镜检查正常的患者区分开来，受试者工作特征曲线下面积为 90%（95% CI，86-94）。MiRFec 评分在第 4 个四分位数（高于 3.09，高风险组）的受试者患晚期结直肠肿瘤的可能性是 miRFec 评分在第 1 个四分位数（低于 2.14，低风险组）的受试者的 8 倍。低风险组的受试者对晚期结直肠肿瘤的检测阳性预测值低于 30%。当我们使用 50% 的特异性截止值时，mirFec 算法识别出 97% 的 CRC 患者，并允许 264 名受试者 (34.4%) 避免结肠镜检查。

结论

基于 2 种 miRNA 和血红蛋白的粪便水平、患者年龄和性别 (miRFec) 的算法将 CRC 患者与非晚期腺瘤患者或结肠镜检查正常的患者区分开来，受试者工作特征曲线下面积值为 90%，避免率为 34%结肠镜检查。将此算法纳入基于 FIT 的 CRC 筛查程序可以提高其有效性和效率。