Perrone Federica, Lampis Andrea, Bertan Claudia, Verderio Paolo, Ciniselli Chiara M, Pizzamiglio Sara, Frattini Milo, Nucifora Martina, Molinari Francesca, Gallino Gianfranco, Gariboldi Manuela, Meroni Emanuele, Leo Ermanno, Pierotti Marco A, Pilotti Silvana
Tumori. 2014 Mar-Apr;100(2):115-21. doi: 10.1177/030089161410000201.
The quantification and molecular characterization of circulating free DNA (cfDNA) have attracted much interest as new and promising, noninvasive means of detecting and monitoring the presence of surgical resectable colorectal cancer (CRC). Instead, the role of cfDNA in the early detection of malignant and premalignant colorectal lesions is still unclear. The aim of this study was to evaluate the predictive power of the quantification and KRAS status of cfDNA in detecting early colorectal lesions in plasma from healthy high-risk subjects.
The study population consisted of 170 consecutive healthy high-risk subjects aged >50 years who participated in the screening program promoted by the Local Health Service (ASL-Milano) for early CRC detection and who underwent endoscopic examination after being found positive at fecal occult blood test (FOBT). Thirty-four participants had malignant lesions consisting of 12 adenocarcinomas (at an early stage in half of the cases) and 22 instances of high-grade intraepithelial neoplasia (HGIN) in adenomas; 73 participants had premalignant lesions (adenomas and hyperplasia), and 63 participants had no lesions. Plasma cfDNA was quantified by quantitative real-time PCR and analyzed for KRAS mutations by a mutant-enriched PCR. KRAS status was assessed also in matched adenocarcinoma and HGIN tissues. The distribution of cfDNA concentrations among FOBT-positive subjects with diagnosed lesion (cases) was compared with that of FOBT-positive subjects without lesions (controls) and its predictive capability (AUC) was assessed.
The predictive capability of cfDNA levels was satisfactory in predicting adenocarcinomas (AUC 0.709; 95% CI, 0.508-0.909) but not HGIN and premalignant lesions. The rate of KRAS mutations in plasma was low (5/170 = 3%) compared with the rate observed in the matched adenocarcinoma and HGIN tissues (45%).
The use of cfDNA quantification to predict adenocarcinoma at an early stage in high-risk (aged >50 years and FOBT positive) subjects seems to be promising but needs more sensitive methods to improve cfDNA detection.
循环游离DNA（cfDNA）的定量分析和分子特征作为检测和监测可手术切除的结直肠癌（CRC）的新的、有前景的非侵入性手段，已引起广泛关注。然而，cfDNA在结直肠癌恶性和癌前病变早期检测中的作用仍不明确。本研究旨在评估cfDNA定量和KRAS状态在检测健康高危人群血浆中早期结直肠病变的预测能力。
研究人群包括170名年龄大于50岁的连续健康高危受试者，他们参加了当地卫生服务机构（ASL - 米兰）推动的早期CRC筛查项目，并在粪便潜血试验（FOBT）呈阳性后接受了内镜检查。34名参与者有恶性病变，包括12例腺癌（其中一半处于早期阶段）和22例腺瘤中的高级别上皮内瘤变（HGIN）；73名参与者有癌前病变（腺瘤和增生），63名参与者无病变。通过定量实时PCR对血浆cfDNA进行定量，并通过突变富集PCR分析KRAS突变情况。还对匹配的腺癌和HGIN组织进行了KRAS状态评估。将已诊断病变的FOBT阳性受试者（病例）中cfDNA浓度分布与无病变的FOBT阳性受试者（对照）进行比较，并评估其预测能力（AUC）。
cfDNA水平在预测腺癌方面的预测能力令人满意（AUC 0.709；95%CI，0.508 - 0.909），但对HGIN和癌前病变的预测能力不佳。与匹配的腺癌和HGIN组织中观察到的突变率（45%）相比，血浆中KRAS突变率较低（5/170 = 3%）。
在高危（年龄大于50岁且FOBT阳性）人群中，使用cfDNA定量预测早期腺癌似乎有前景，但需要更敏感的方法来提高cfDNA检测。
