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Serial circulating tumor DNA profiling predicts tumor recurrence after liver transplantation for liver cancer

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Abstract

Background

Minimal residual disease (MRD) is proposed to be responsible for tumor recurrence. The role of circulating tumor DNA (ctDNA) to detect MRD, monitor recurrence, and predict prognosis in liver cancer patients undergoing liver transplantation (LT) remains unrevealed.

Methods

Serial blood samples were collected to profile ctDNA mutational changes. Baseline ctDNA mutational profiles were compared with those of matched tumor tissues. Correlations between ctDNA status and recurrence rate (RR) and recurrence-free survival (RFS) were analyzed, respectively. Dynamic change of ctDNA was monitored to predict tumor recurrence.

Results

Baseline mutational profiles of ctDNA were highly concordant with those of tumor tissues (median, 89.85%; range 46.2–100%) in the 74 patients. Before LT, positive ctDNA status was associated with higher RR (31.7% vs 11.5%; p = 0.001) and shorter RFS than negative ctDNA status (17.8 vs 19.4 months; p = 0.019). After LT, the percentage of ctDNA positivity decreased (17.6% vs 47.0%; p < 0.001) and patients with positive ctDNA status had higher RR (46.2% vs 21.3%; p < 0.001) and shorter RFS (17.2 vs 19.2 months; p = 0.010). Serial ctDNA profiling demonstrated patients with decreased or constant negative ctDNA status had lower RR (33.3% vs 50.0%; p = 0.015) and favorable RFS (18.2 vs 15.0 months, p = 0.003) than those with increased or constant positive ctDNA status. Serial ctDNA profiling predicted recurrence months ahead of imaging evidence and serum tumor biomarkers.

Conclusions

ctDNA could effectively detect MRD and predict tumor recurrence in liver cancer patients undergone LT.

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Data availability

The raw data generated in this study are not publicly available since the sequencing used in this study was a commercial service paid by the patients. However, the derived data supporting the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This study was jointly supported by Shanghai Municipal Health Commission (20224Y0285, R2022-010), National Natural Science Foundation of China (No.82150004), Natural Science Foundation of Shanghai (No.20ZR1473100), and Shanghai Municipal Key Clinical Specialty.

Author information

Author notes

  1. Ao Huang, De-Zhen Guo and Xuan Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, China

    Ao Huang, De-Zhen Guo, Shi-Yu Zhang, Xin Zhang, Xiu-Tao Fu, Yu-Peng Wang, Guo-Huan Yang, Qi-Man Sun, Yi-Feng He, Kang Song, Xiao-Wu Huang, Xin-Rong Yang, Wei-Ren Liu, Zhen-Bin Ding, Ying-Hong Shi, Jia Fan & Jian Zhou

  2. Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China

    Ao Huang, De-Zhen Guo, Shi-Yu Zhang, Xin Zhang, Xiu-Tao Fu, Yu-Peng Wang, Guo-Huan Yang, Qi-Man Sun, Yi-Feng He, Kang Song, Xiao-Wu Huang, Xin-Rong Yang, Wei-Ren Liu, Zhen-Bin Ding, Ying-Hong Shi, Jia Fan & Jian Zhou

  3. Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

    Ao Huang, De-Zhen Guo, Shi-Yu Zhang, Xin Zhang, Xiu-Tao Fu, Yu-Peng Wang, Guo-Huan Yang, Qi-Man Sun, Yi-Feng He, Kang Song, Xiao-Wu Huang, Xin-Rong Yang, Wei-Ren Liu, Zhen-Bin Ding, Ying-Hong Shi, Jia Fan & Jian Zhou

  4. Key Laboratory of Clinical in Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, 310030, China

    Xuan Zhang

  5. GenomiCare Biotechnology (Shanghai) Co., Ltd., 5th Floor, Building #2, No. 111 Xiangke Road, Shanghai, 201210, China

    Xuan Zhang & Ying Sun

  6. Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, 200031, China

    Zhen-Bin Ding & Jian Zhou

  7. Institute of Biomedical Sciences, Fudan University, Shanghai, 200032, China

    Jia Fan & Jian Zhou

  8. State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China

    Jia Fan & Jian Zhou

Authors
  1. Ao Huang
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  2. De-Zhen Guo
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  5. Shi-Yu Zhang
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  19. Jian Zhou
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Contributions

All authors contributed to the study’s conception and design. Material preparation, data collection and analysis were performed by AH, D-ZG, XZ, YS and S-YZ. The first draft of the manuscript was written by AH and XZ and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jian Zhou.

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Conflict of interest

Ao Huang, De-Zhen Guo, Xuan Zhang, Ying Sun, Shi-Yu Zhang, Xin Zhang, Xiu-Tao Fu, Yu-Peng Wang, Guo-Huan Yang, Qi-Man Sun, Yi-Feng He, Kang Song, Xiao-Wu Huang, Xin-Rong Yang, Wei-Ren Liu, Zhen-Bin Ding, Ying-Hong Shi and Jia Fan and Jian Zhou declares that they have no conflict of interest. The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5). Informed consent was obtained from all patients for being included in the study.

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Huang, A., Guo, DZ., Zhang, X. et al. Serial circulating tumor DNA profiling predicts tumor recurrence after liver transplantation for liver cancer. Hepatol Int 18, 254–264 (2024). https://doi.org/10.1007/s12072-023-10594-x

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