Wang Cheng, Gu Huihui, Cai Jia, Zhu Chuandong, Zheng Qin, Xu Hanfeng, Wang Lixue, Wan Yuan
Department of Radiation Oncology, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine (The Second Hospital of Nanjing), Jiangsu, Nanjing, China.
Department of Oncology, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine (The Second Hospital of Nanjing), Jiangsu, Nanjing, China.
Front Oncol. 2025 Jan 16;14:1506968. doi: 10.3389/fonc.2024.1506968. eCollection 2024.
Circulating tumor cells (CTCs) have attracted significant interest as a biomarker for cancer diagnosis. In this study, we judiciously constructed a recombinant MUC1-dependent adenovirus (rAdF35-MUC1) that can selectively replicate and overexpress copepod super green fluorescent proteins (copGFP) in MUC1-positive tumor cells to investigate its role in the detection of CTCs.
We conducted a comparative study between rAdF35-MUC1 and the existing hTERT-dependent adenovirus (rAdF35-hTERT). Breast cancer cell lines and healthy human peripheral blood mononuclear cells (PBMCs) were infected with both viral constructs to evaluate infection efficiency and the incidence of false-positive cells. CTC Model Samples were employed to determine detection rates, and clinical samples from breast cancer patients were analyzed to preliminarily evaluate the efficacy of CTC detection in a clinical context.
In preclinical and clinical studies, rAdF35-MUC1 exhibited a significantly high detection efficiency for breast cancer cells, outperforming the existing hTERT-dependent adenovirus (rAdF35-hTERT), especially in detecting CTCs at low quantities. Moreover, rAdF35-MUC1 demonstrated reduced incidence of false positives in healthy PBMCs compared to rAdF35-hTERT.
In brief, rAdF35-MUC1 emerges as a potent tool for the sensitive and specific identification of CTCs derived from breast cancer patients, holding clinical translation potential for advancing cancer (early) diagnosis, treatment monitoring, and prognosis.
循环肿瘤细胞（CTCs）作为一种癌症诊断生物标志物已引起广泛关注。在本研究中，我们精心构建了一种重组MUC1依赖性腺病毒（rAdF35-MUC1），它能在MUC1阳性肿瘤细胞中选择性复制并过表达桡足类超绿色荧光蛋白（copGFP），以研究其在CTCs检测中的作用。
我们对rAdF35-MUC1和现有的hTERT依赖性腺病毒（rAdF35-hTERT）进行了比较研究。用这两种病毒构建体感染乳腺癌细胞系和健康人外周血单个核细胞（PBMCs），以评估感染效率和假阳性细胞的发生率。采用CTCs模型样本确定检测率，并对乳腺癌患者的临床样本进行分析，以初步评估CTCs检测在临床环境中的效果。
在临床前和临床研究中，rAdF35-MUC1对乳腺癌细胞表现出显著高的检测效率，优于现有的hTERT依赖性腺病毒（rAdF35-hTERT），尤其是在检测少量CTCs时。此外，与rAdF35-hTERT相比，rAdF35-MUC1在健康PBMCs中显示出较低的假阳性发生率。
简而言之，rAdF35-MUC1成为一种用于灵敏且特异鉴定乳腺癌患者来源CTCs的有力工具，在推进癌症（早期）诊断、治疗监测和预后方面具有临床转化潜力。
