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Molecular Diagnostics

A liquid biopsy signature predicts lymph node metastases in T1 oesophageal squamous cell carcinoma: implications for precision treatment strategy

British Journal of Cancer volume 127, pages 2052–2059 (2022)Cite this article

Subjects

Abstract

Background

The treatment strategies for T1 oesophageal squamous cell carcinoma (ESCC) patients with or without lymph node metastasis (LNM) are different. Given the advantages of the minimally invasive, sensitive and real-time detection, liquid biopsy has become an important cancer diagnostic and prognostic tool.

Methods

MiRNA array and small-RNA sequencing were performed. Then, 222 formalin-fixed and paraffin-embedded tumour samples and 229 pretreatment serum samples from T1 ESCC patients were used to verify and evaluate the results.

Results

We demonstrated that serum miR-20b-5p could predict LNM in T1 ESCC patients. The AUC for serum miR-20b-5p was higher (0.827) than those for lymphovascular invasion (LVI) (0.751, P = 0.2128), invasion depth (0.662, P = 0.0027) and tumour differentiation grade (0.634, P = 0.0019). A nomogram for predicting LNM with three independent significant predictors (miR-20b-5p, LVI and invasion depth) was constructed with a concordance index of 0.931. Serum miR-20b-5p was also significantly correlated with disease-free survival (P < 0.001). An algorithm of improved T1 ESCC treatment strategy after biopsy and/or after endoscopic resection based on serum miR-20b-5p level was constructed.

Conclusions

This study suggests that serum miR-20b-5p is a potential biomarker for predicting LNM and can be helpful for precise clinical decision-making strategies and improve treatment outcomes for T1 ESCC patients.

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Fig. 1
Fig. 2
Fig. 3: Discovery and validation of differentially expressed miRNAs in FFPE tumour samples between T1 ESCC with and without LNM.
Fig. 4: Discovery of differentially expressed miRNAs in serum from ESCC with and without LNM by small-RNA sequencing, and serum miR-20b-5p predicting LNM and prognosis of T1 ESCC in the evaluation cohort.
Fig. 5: An algorithm of improved T1 ESCC treatment strategy after biopsy and/or after endoscopic resection based on serum miR-20b-5p level.

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Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the National Key Research and Development Programme of China (no. 2016YFA0500303 to Yongmei Song), the National Natural Science Foundation of China (81872398 to Yongmei Song and 81402463 to Liyan Xue), and the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2019PT310027 to Yongmei Song).

Author information

Author notes

  1. These authors contributed equally: Liyan Xue, Zitong Zhao, Minjie Wang.

Authors and Affiliations

  1. Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Liyan Xue, Xuemin Xue, Linxiu Liu, Bingzhi Wang, Zhuo Li, Zhaoyang Yang & Ning Lu

  2. State Key Laboratory of Molecular Oncology, Key Laboratory of Cancer and Microbiome, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Zitong Zhao, Liying Ma, Qimin Zhan & Yongmei Song

  3. Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Minjie Wang

  4. Department of Medical Record, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Hua Lin

  5. National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Shaoming Wang

  6. Laboratory of Molecular Oncology, Peking University Cancer Hospital, Beijing, China

    Qimin Zhan

Authors
  1. Liyan Xue
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  2. Zitong Zhao
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  10. Zhuo Li
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Contributions

YS, QZ and NL designed this study. LX, ZZ, MW, LM, HL, SW, XX, LL, BW, ZL and ZY collected clinical samples and clinical information. ZZ and LX performed the experiments and conducted data analysis. LX and ZZ wrote the manuscript.

Corresponding authors

Correspondence to Ning Lu, Qimin Zhan or Yongmei Song.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

This study was performed in accordance with the Declaration of Helsinki and was conducted after obtaining approval from the Independent Ethics Committee at the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (No. NCC2598). Informed consent was obtained from all patients. All methods were performed in accordance with relevant guidelines and regulations.

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Xue, L., Zhao, Z., Wang, M. et al. A liquid biopsy signature predicts lymph node metastases in T1 oesophageal squamous cell carcinoma: implications for precision treatment strategy. Br J Cancer 127, 2052–2059 (2022). https://doi.org/10.1038/s41416-022-01997-y

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