Silva J M, Rodriguez R, Garcia J M, Muñoz C, Silva J, Dominguez G, Provencio M, España P, Bonilla F
Department of Medical Oncology, Clinica Puerta de Hierro, 28035-Madrid, Spain.
Gut. 2002 Apr;50(4):530-4. doi: 10.1136/gut.50.4.530.
Although circulating tumour DNA has been detected in patients with different types of cancer, little is known of free RNA in cancer patients.
We investigated the presence of RNA from epithelial tumours in plasma from patients with colorectal carcinomas, and its correlation with tumour characteristics and circulating tumour cells.
beta-actin mRNA was analysed to assess the viability of plasma RNA in samples from 53 patients with colonic cancer and 25 controls. Subsequently, nested primers were used to detect the presence of cytokeratin 19 (CK19) and carcinoembryonic antigen (CEA) RNA in the same samples. Nine clinicopathological parameters were studied to correlate the molecular and clinical parameters. Additionally, we investigated for micrometastases in blood in 18 of these patients and in 10 of the controls samples.
All samples had detectable quantities of beta-actin RNA. In the controls, one case (4%) was positive for CEA and five (20%) for CK19 RNA; of the 53 patients, 17 cases (32%) were positive for CEA and 39 (73.6%) for CK19 RNA. This was statistically significant (p=0.000001). Advanced stages (p=0.03) and soluble CEA status (p=0.03) were associated with the presence of CEA, CK19, or both RNAs in plasma. Lymph node metastases (p=0.06) and vascular invasion (p=0.07) were almost significant. On the basis of these results, we examined the possible presence of micrometastases in blood in several of these patients. The presence of plasma tumour RNA was found to be associated with circulating tumour cells in blood (p=0.04).
Epithelial tumour RNA is detectable in plasma from colon cancer patients. This molecular event is associated with advanced stages and circulating tumour cells. Our results could offer new approaches in the diagnosis and monitoring of colon cancer.
尽管已在不同类型癌症患者中检测到循环肿瘤DNA,但对癌症患者中的游离RNA了解甚少。
我们研究了结肠直肠癌患者血浆中上皮肿瘤RNA的存在情况,及其与肿瘤特征和循环肿瘤细胞的相关性。
分析β-肌动蛋白mRNA以评估53例结肠癌患者和25例对照样本中血浆RNA的活力。随后,使用巢式引物检测同一样本中细胞角蛋白19(CK19)和癌胚抗原(CEA)RNA的存在情况。研究了九个临床病理参数以关联分子和临床参数。此外,我们在其中18例患者和10例对照样本中检测了血液中的微转移情况。
所有样本均检测到可定量的β-肌动蛋白RNA。在对照组中,1例(4%)CEA呈阳性,5例(20%)CK19 RNA呈阳性;在53例患者中,17例(32%)CEA呈阳性,39例(73.6%)CK19 RNA呈阳性。这具有统计学意义(p = 0.000001)。晚期(p = 0.03)和可溶性CEA状态(p = 0.03)与血浆中CEA、CK19或两者RNA的存在相关。淋巴结转移(p = 0.06)和血管侵犯(p = 0.07)几乎具有统计学意义。基于这些结果,我们检查了其中一些患者血液中可能存在的微转移情况。发现血浆肿瘤RNA的存在与血液中的循环肿瘤细胞相关(p = 0.04)。
在结肠癌患者血浆中可检测到上皮肿瘤RNA。这一分子事件与晚期阶段和循环肿瘤细胞相关联。我们的结果可能为结肠癌的诊断和监测提供新方法。