Enhanced detection of circulating tumor cells using a MUC1 promoter-driven recombinant adenovirus

IntroductionCirculating 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...

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Main Authors: Cheng Wang, Huihui Gu, Jia Cai, Chuandong Zhu, Qin Zheng, Hanfeng Xu, Lixue Wang, Yuan Wan
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2024.1506968/full
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author Cheng Wang
Huihui Gu
Jia Cai
Chuandong Zhu
Qin Zheng
Hanfeng Xu
Lixue Wang
Yuan Wan
author_facet Cheng Wang
Huihui Gu
Jia Cai
Chuandong Zhu
Qin Zheng
Hanfeng Xu
Lixue Wang
Yuan Wan
author_sort Cheng Wang
collection DOAJ
description IntroductionCirculating 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.MethodsWe 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.ResultsIn 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.ConclusionIn 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.
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spelling doaj-art-ac0f4d6fc56f4078ab77e329231193552025-01-16T06:10:34ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-01-011410.3389/fonc.2024.15069681506968Enhanced detection of circulating tumor cells using a MUC1 promoter-driven recombinant adenovirusCheng Wang0Huihui Gu1Jia Cai2Chuandong Zhu3Qin Zheng4Hanfeng Xu5Lixue Wang6Yuan Wan7Department of Radiation Oncology, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine (The Second Hospital of Nanjing), Jiangsu, Nanjing, ChinaDepartment of Radiation Oncology, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine (The Second Hospital of Nanjing), Jiangsu, Nanjing, ChinaDepartment of Radiation Oncology, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine (The Second Hospital of Nanjing), Jiangsu, Nanjing, ChinaDepartment of Oncology, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine (The Second Hospital of Nanjing), Jiangsu, Nanjing, ChinaDepartment of Oncology, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine (The Second Hospital of Nanjing), Jiangsu, Nanjing, ChinaDepartment of Oncology, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine (The Second Hospital of Nanjing), Jiangsu, Nanjing, ChinaDepartment of Radiation Oncology, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine (The Second Hospital of Nanjing), Jiangsu, Nanjing, ChinaThe Pq Laboratory of BiomeDx/Rx, Department of Biomedical Engineering, Binghamton University, Binghamton, NY, United StatesIntroductionCirculating 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.MethodsWe 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.ResultsIn 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.ConclusionIn 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.https://www.frontiersin.org/articles/10.3389/fonc.2024.1506968/fullbreast cancercirculating tumor cellDF3/MUC1hTERTadenovirus
spellingShingle Cheng Wang
Huihui Gu
Jia Cai
Chuandong Zhu
Qin Zheng
Hanfeng Xu
Lixue Wang
Yuan Wan
Enhanced detection of circulating tumor cells using a MUC1 promoter-driven recombinant adenovirus
Frontiers in Oncology
breast cancer
circulating tumor cell
DF3/MUC1
hTERT
adenovirus
title Enhanced detection of circulating tumor cells using a MUC1 promoter-driven recombinant adenovirus
title_full Enhanced detection of circulating tumor cells using a MUC1 promoter-driven recombinant adenovirus
title_fullStr Enhanced detection of circulating tumor cells using a MUC1 promoter-driven recombinant adenovirus
title_full_unstemmed Enhanced detection of circulating tumor cells using a MUC1 promoter-driven recombinant adenovirus
title_short Enhanced detection of circulating tumor cells using a MUC1 promoter-driven recombinant adenovirus
title_sort enhanced detection of circulating tumor cells using a muc1 promoter driven recombinant adenovirus
topic breast cancer
circulating tumor cell
DF3/MUC1
hTERT
adenovirus
url https://www.frontiersin.org/articles/10.3389/fonc.2024.1506968/full
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