既往未经治疗的转移性结直肠癌患者血液RNA生物标志物与循环肿瘤细胞的关联
Associations of blood RNA biomarkers and circulating tumour cells in patients with previously untreated metastatic colorectal cancer.
作者信息
Valladares-Ayerbes Manuel, Toledano-Fonseca Marta, Graña Begoña, Jimenez-Fonseca Paula, Pulido-Cortijo Gema, Gil Silvia, Sastre Javier, Salud Antonieta, Rivera Fernando, Salgado Mercedes, García-Alfonso Pilar, López López Rafael, Guillén-Ponce Carmen, Rodríguez-Ariza Antonio, Vieitez Jose Mª, Díaz-Rubio Eduardo, Aranda Enrique
机构信息
Department of Medical Oncology, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina (IBIS), Seville, Spain.
Department of Medical Oncology, IMIBIC, Universidad de Córdoba, CIBERONC, Instituto de Salud Carlos III, Hospital Universitario Reina Sofía, Córdoba, Spain.
出版信息
BMC Cancer. 2025 Apr 21;25(1):743. doi: 10.1186/s12885-025-14098-9.
BACKGROUND
In patients with metastatic colorectal cancer, analysis of the number of basal circulating tumour cells (bCTCs) has been shown to be a strong prognostic indicator. In this study, we aim to explore the potential associations between whole blood mRNA and microRNA expression profiles and bCTC counts, tumour mutations and prognosis in untreated metastatic colorectal cancer patients.
METHODS
A total of 151 patients previously screened for inclusion in two clinical trials (VISNÚ1 and VISNÚ2) were enrolled in this study. Real-time quantitative PCR (qPCR) analyses were performed to determine the whole blood expression of selected RNAs (mRNAs and microRNAs) involved in the metastatic process. The CellSearch system was used to enumerate circulating tumour cells. The primary objective was to correlate RNA expression with the number of bCTCs, while the secondary objectives were to investigate the relationship between the levels of circulating RNA biomarkers in whole blood and the clinical, pathological, and molecular characteristics and prognosis of patients with metastatic colorectal cancer.
RESULTS
bCTC count was significantly associated with AGR2 mRNA in the entire cohort of 151 patients. AGR2, ADAR1 and LGR5 were associated with the number of bCTC, both in the subgroup with bCTC ≥ 3 and in the subgroup with native RAS/BRAF/PIK3 CA tumours. In patients with RAS/BRAF/PIK3 CA mutations no correlations with bCTC were detected, but an upregulation of miR-224-5p and the stemness marker LGR5 and a downregulation of immune regulatory CD274 were found. Lower levels of miR-106a-5p/miR-26a-5p were associated with shorter overall survival, with independent statistical significance in the multivariate analysis.
CONCLUSIONS
A correlation was identified between the levels of a subset of whole blood RNAs, including AGR2, ADAR1, and LGR5, and the number of bCTC and RAS/BRAF/PIK3 CA mutational status. Furthermore, another set of whole blood RNAs, specifically miR-106a-5p and miR-26a-5p, was found to be associated with poor prognosis. This may be helpful for risk stratification.
TRIAL REGISTRATION
Clinical Trials Gov. NCT01640405 and NCT01640444. Registered on 13 June 2012. https://clinicaltrials.gov/ .
背景
在转移性结直肠癌患者中，基础循环肿瘤细胞（bCTC）数量分析已被证明是一个强有力的预后指标。在本研究中，我们旨在探讨未经治疗的转移性结直肠癌患者全血mRNA和微小RNA表达谱与bCTC计数、肿瘤突变及预后之间的潜在关联。
方法
本研究纳入了151名先前筛选以纳入两项临床试验（VISNÚ1和VISNÚ2）的患者。采用实时定量PCR（qPCR）分析来确定参与转移过程的选定RNA（mRNA和微小RNA）的全血表达。使用CellSearch系统对循环肿瘤细胞进行计数。主要目的是将RNA表达与bCTC数量相关联，次要目的是研究全血中循环RNA生物标志物水平与转移性结直肠癌患者的临床、病理、分子特征及预后之间的关系。
结果
在151名患者的整个队列中，bCTC计数与AGR2 mRNA显著相关。AGR2、ADAR1和LGR5与bCTC数量相关，在bCTC≥3的亚组以及具有野生型RAS/BRAF/PIK3 CA肿瘤的亚组中均如此。在RAS/BRAF/PIK3 CA突变患者中，未检测到与bCTC的相关性，但发现miR - 224 - 5p和干性标志物LGR5上调以及免疫调节因子CD274下调。较低水平的miR - 106a - 5p/miR - 26a - 5p与较短的总生存期相关，在多变量分析中具有独立统计学意义。
结论
确定了包括AGR2、ADAR1和LGR5在内的全血RNA子集水平与bCTC数量及RAS/BRAF/PIK3 CA突变状态之间的相关性。此外，发现另一组全血RNA，特别是miR - 106a - 5p和miR - 26a - 5p，与不良预后相关。这可能有助于进行风险分层。
试验注册
Clinical Trials Gov. NCT01640405和NCT01640444。于2012年6月13日注册。https://clinicaltrials.gov/ 。
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