Maximum allele frequency observed in plasma: A potential indicator of liquid biopsy sensitivity

Tang,Yong; Liu,Xianling; Ou,Zhu'an; He,Zhe; Zhu,Qihang; Wang,Ye; Yang,Mei; Ye,Junyi; Han‑Zhang,Han; Qiao,Guibin

doi:10.3892/ol.2019.10490

Maximum allele frequency observed in plasma: A potential indicator of liquid biopsy sensitivity

Authors:
- Yong Tang
- Xianling Liu
- Zhu'an Ou
- Zhe He
- Qihang Zhu
- Ye Wang
- Mei Yang
- Junyi Ye
- Han Han‑Zhang
- Guibin Qiao
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Affiliations: Department of Thoracic Surgery, General Hospital of Southern Theater Command, Guangzhou, Guangdong 510010, P.R. China, Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China, Department of Cadre Treatment, The Third Affiliated Hospital of Kunming Medical University (Yunnan Province Tumor Hospital), Kunming, Yunnan 650118, P.R. China, Burning Rock Biotech, Guangzhou, Guangdong 510300, P.R. China, Department of Thoracic Surgery, Guangdong General Hospital, Guangzhou, Guangdong 510245, P.R. China
Published online on: June 18, 2019 https://doi.org/10.3892/ol.2019.10490
Pages: 2118-2124

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Abstract

Personalized medicine is revolutionizing the diagnosis and treatment of cancer; however, for personalized medicine to be used accurately, patient information is essential to determine the appropriate diagnosis, prognosis and treatment. The detection of genomic mutations in liquid biopsy samples is a non‑invasive method of characterizing the genotype of a tumor. However, next generation sequencing‑based plasma genotyping only has a sensitivity of ~70%. Identifying potential indicators that may reflect the sensitivity of a liquid biopsy analysis could offer important information for its clinical application. In the present study, 47 pairs of patient‑matched plasma and tumor tissue samples obtained from patients with advanced lung cancer were sequenced using a panel of 56 cancer‑associated genes. The plasma maximum allele frequency (Max AF) was identified as a novel biomarker to indicate the sensitivity of plasma genotyping. Using the identified somatic mutations in patient tissue biopsy samples as a reference, the sensitivity of the corresponding patient plasma test was investigated. The by‑variant sensitivity of the plasma test was 68.1%, with 79 matched and 37 missed genetic aberrances. The by‑patient sensitivity was calculated as 83%. Patients with a high plasma Max AF value (>2.2%) demonstrated a higher concordance with the range of mutations identified in the patient‑matched tissue samples. The Max AF observed in patient plasma samples was positively correlated with liquid biopsy sensitivity and could be used as a potential indicator of liquid biopsy sensitivity. Therefore, patients with a low plasma Max AF (≤2.2%) may need to undergo further tissue biopsy to allow personalized oncology treatment. In summary, the present study may offer a non‑invasive testing method for a sub‑group of patients with advanced lung cancer.

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