检测肺腺癌的 BCAT1 和 IKZF1 的 DNA 甲基化的血液检测。

A blood test measuring DNA methylation of BCAT1 and IKZF1 for detection of lung adenocarcinoma.

机构信息

Department of Respiratory Sleep Medicine and Ventilation, Flinders Medical Centre, Bedford Park, SA, Australia.

Cancer Impact Program, Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia.

出版信息

Cancer Treat Res Commun. 2024;40:100838. doi: 10.1016/j.ctarc.2024.100838. Epub 2024 Aug 7.

DOI:10.1016/j.ctarc.2024.100838

PMID:39154541

Abstract

BACKGROUND

Colorectal (CRC) and lung adenocarcinoma share many genetic and pathological similarities. A circulating tumor DNA (ctDNA) test for CRC may also be useful for detection of lung adenocarcinoma. This study determined if a methylated BCAT1/IKZF1 ctDNA test for CRC can be used for detection of lung adenocarcinoma.

PATIENTS AND METHODS

Circulating cell free DNA (ccfDNA) was extracted from plasma collected prospectively from healthy controls, patients in remission from CRC, patients with lung adenocarcinoma, and patients with isolated metastatic CRC lung lesions. Plasma ccfDNA was bisulfite converted and assessed for methylated BCAT1/IKZF1 by quantitative real-time PCR. Comparisons between the different patient groups for a positive ctDNA test (BCAT1 and/or IKZF1) and ctDNA levels (% of total ccfDNA), as well as any associations with clinicopathological and demographic features, were assessed.

RESULTS

Methylated BCAT1/IKZF1 ctDNA was detected in 18/39 (46.2 %) patients with lung adenocarcinoma, which was significantly (p < 0.001) higher compared to healthy controls (49/606; 8.1 %) and patients in remission from CRC (22/171, 12.9 %). Patients with stage III/IV lung adenocarcinoma had higher BCAT1/IKZF1 ctDNA positivity compared to stage I/II cases (68.2 % vs 17.7 %, p < 0.01), where a significantly higher proportion tested positive for methylated IKZF1 ctDNA alone (54.6 % vs 5.9 %, p < 0.001). There was no difference in BCAT1/IKZF1 ctDNA test positivity between patients with stage IV primary lung adenocarcinoma (n = 17) compared to lung-metastasising CRC cases (n = 17; 70.6 % v 64.3 %).

CONCLUSION

A ctDNA test measuring methylated BCAT1/IKZF1 can sensitively detect lung adenocarcinoma and may be a promising aid for detection of advanced disease.

CLINICAL TRIAL REGISTRATIONS

Australian and New Zealand Clinical Trials Registry, www.anzctr.org.au, ACTRN12616001138471, ACTRN12611000318987.

摘要

背景

结直肠癌（CRC）和肺腺癌具有许多遗传和病理上的相似性。用于 CRC 的循环肿瘤 DNA（ctDNA）检测也可能有助于检测肺腺癌。本研究旨在确定用于 CRC 的甲基化 BCAT1/IKZF1 ctDNA 检测是否可用于检测肺腺癌。

患者和方法

前瞻性采集来自健康对照者、CRC 缓解期患者、肺腺癌患者和孤立性转移性 CRC 肺病变患者的血浆，提取游离循环细胞 DNA（ccfDNA）。用亚硫酸氢盐对血浆 ccfDNA 进行处理，并通过定量实时 PCR 检测甲基化 BCAT1/IKZF1。评估不同患者组中 ctDNA 检测阳性（BCAT1 和/或 IKZF1）和 ctDNA 水平（总 ccfDNA 的百分比）的差异，以及与临床病理和人口统计学特征的任何关联。

结果

18/39（46.2%）例肺腺癌患者检测到甲基化 BCAT1/IKZF1 ctDNA，明显高于健康对照者（49/606；8.1%）和 CRC 缓解期患者（22/171；12.9%）（p<0.001）。III/IV 期肺腺癌患者的 BCAT1/IKZF1 ctDNA 阳性率高于 I/II 期患者（68.2%比 17.7%，p<0.01），其中单独检测到甲基化 IKZF1 ctDNA 阳性的比例明显更高（54.6%比 5.9%，p<0.001）。IV 期原发性肺腺癌患者（n=17）与肺转移 CRC 病例（n=17）之间的 BCAT1/IKZF1 ctDNA 检测阳性率无差异（70.6%比 64.3%）。