Circulating Tumor DNA Analyses Predict Disease Recurrence in Non-Muscle-Invasive Bladder Cancer

Jinghua Zhang; Daofeng Dai; Junqiang Tian; Lifeng Li; Jing Bai; Yaping Xu; Zhiping Wang; Aifa Tang

doi:10.3389/fonc.2021.657483

Circulating Tumor DNA Analyses Predict Disease Recurrence in Non-Muscle-Invasive Bladder Cancer

Front Oncol. 2021 Apr 28:11:657483. doi: 10.3389/fonc.2021.657483. eCollection 2021.

Authors

Jinghua Zhang^{1

2}, Daofeng Dai^{2

3}, Junqiang Tian⁴, Lifeng Li⁵, Jing Bai⁵, Yaping Xu⁵, Zhiping Wang⁴, Aifa Tang^{2

6}

Affiliations

¹ College of Life Sciences, Henan Agricultural University, Zhengzhou, China.
² Health Science Center, The First Affiliated Hospital of Shenzhen University, and Guangdong Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors, Shenzhen Second People's Hospital, Shenzhen, China.
³ Jiangxi Otorhinolaryngology Head and Neck Surgery Institute, Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.
⁴ Key Laboratory of Gansu Province for Urological Diseases, Department of Urology of Lanzhou University Second Hospital, Urology Institute of Lanzhou University Second Hospital, Lanzhou, China.
⁵ Geneplus-Beijing Institute, Beijing, China.
⁶ Shenzhen Luohu Hospital Group, The Third Affiliated Hospital of Shenzhen University, Shenzhen, China.

Abstract

Circulating tumor DNA (ctDNA) can be a prognostic biomarker for non-muscle-invasive bladder cancer (NMIBC); however, targeted sequencing has not been performed to detect ctDNA in NMIBC. We applied targeted sequencing based on an 861-gene panel to determine mutations in tumor tissue DNA and plasma ctDNA in 82 NMIBC patients receiving transurethral resection (TUR) of bladder followed by immunotherapy. We detected 476 and 165 somatic variants in tumor DNA from 82 NMIBC patients (100%) and ctDNA from 54 patients (65.85%), respectively. Patients with high heterogeneity in tumor DNA had a significantly shorter disease-free survival than those with low heterogeneity. Tumor-derived alterations were detectable in plasma of 43 patients (52.44%). The concordance of somatic variants between tumor DNA and plasma ctDNA were higher in patients with T1 stage (p < 0.0001) and tumor size ≥3 cm (p = 0.0002). Molecular tumor burden index (mTBI) in ctDNA positively correlated with larger tumor size (p = 0.0020). A higher mTBI was an independent predictor of recurrence after TUR of bladder followed by immunotherapy. Analysis of ctDNA based on targeted sequencing is a promising approach to predict disease recurrence for NMIBC patients receiving TUR of bladder followed by immunotherapy.

Keywords: chemotherapy; circulating tumor DNA; molecular tumor burden index; non-muscle-invasive bladder cancer; prognostic biomarker; targeted sequencing.