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Vessels that encapsulate tumor clusters (VETC) pattern predicts the efficacy of adjuvant TACE in hepatocellular carcinoma

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Abstract

Purpose

Postoperative adjuvant trans-catheter arterial chemoembolization (TACE) is regarded as a common strategy for hepatocellular carcinoma (HCC) patients at a high risk of recurrence. However, there are currently no clinically available biomarkers to predict adjuvant TACE response. Vessels that encapsulate tumor clusters (VETC) can be used as an independent predictor of HCC prognosis. In this study, we aimed to explore whether the VETC pattern could predict adjuvant TACE benefit.

Methods

Vascular pattern and HIF-1α expression were detected in immunohistochemistry. The survival benefit of adjuvant TACE therapy for patients with or without VETC pattern (VETC+ /VETC−) was evaluated.

Results

The adjuvant TACE therapy obviously improved the TTR and OS in VETC+ patients, while adjuvant TACE therapy could not benefit from VETC− patients. Univariate and multivariate analysis revealed that adjuvant TACE therapy significantly improved the TTR and OS in VETC+ patients, but not in VETC- patients. In addition, the VETC+ , but not VETC− , patients could benefit from adjuvant TACE therapy in patients with high-risk factors of vascular invasion, larger tumor or multiple tumor. The mechanistic investigations revealed that the favorable efficacy of adjuvant TACE on VETC+ patients, but not VETC− ones, may be not due to the activation of HIF-1α pathway.

Conclusion

The VETC pattern may represent a novel and reliable factor for selecting HCC patients who may benefit from adjuvant TACE therapy, and the combination of VETC pattern and tumor characteristics may help stratify patients’ outcomes and responses to adjuvant TACE therapy.

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Data availability

All data generated or analyzed during this study are included in this article and its online supplementary material files. Further enquiries can be directed to the corresponding author.

Abbreviations

HCC:

Hepatocellular carcinoma

TACE:

Adjuvant trans-catheter arterial chemoembolization

VETC:

Vessels that encapsulate tumor clusters

TTR:

Time to recurrence

OS:

Overall survival

HIF-1α:

Hypoxia inducible factor-1α

EMT:

Epithelial–mesenchymal transformation

CT:

Computed tomography

MRI:

Magnetic resonance imaging

TNM:

Tumor node metastasis

BCLC:

Barcelona clinical liver cancer

IHC:

Immunohistochemical

AFP:

α-Fetoprotein

PRS:

Post-recurrence survival

95% CI:

95% Confidence intervals

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Acknowledgements

We gratefully acknowledge the pathological files provided by the pathology department of Sun Yat-Sen University Cancer Center.

Funding

This work was supported as follow: 1. Youth Project of National Natural Science Foundation of China (81902971); 2. Guangdong Provincial Education Department key platform and scientific research projects (2018KTSCX187); 3. Guangzhou key medical discipline construction project fund.

Author information

Author notes

  1. Jia-hong Wang, Xiao-shan Li, and Hong-sheng Tang contributed equally to this work.

  2. Shu-Zhong Cui and Jin Wang jointly supervised this work.

Authors and Affiliations

  1. Department of Abdominal Surgery, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, 510095, Guangdong, China

    Jia-hong Wang, Hong-sheng Tang, Run-ya Fang, Yan-lin Feng, Tian-pei Guan, Qiang Ruan, Jin Wang & Shu-Zhong Cui

  2. Department of Medical Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, 510095, Guangdong, China

    Xiao-shan Li

  3. Department of Pathology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, 510095, Guangdong, China

    Jing-jing Song

Authors
  1. Jia-hong Wang
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Contributions

SZC and JW participated in the study conception and design. JHW, XSL, and HST participated in case selection and experiments. JHW, RYF and JJS performed experiment in vitro and in vivo. JHW, XSL and YLF carried out the data collection. HST, TPG and QR performed the scoring of immunohistochemical staining. SZC, JHW and JW performed the data analysis and writing of the manuscript. All the authors read and approved the final manuscript.

Corresponding authors

Correspondence to Jin Wang or Shu-Zhong Cui.

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Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

The study was approved by the Institutional Review Board and Human Ethics Committee of Affiliated Cancer Hospital & Institute of Guangzhou Medical University.

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Wang, Jh., Li, Xs., Tang, Hs. et al. Vessels that encapsulate tumor clusters (VETC) pattern predicts the efficacy of adjuvant TACE in hepatocellular carcinoma. J Cancer Res Clin Oncol 149, 4163–4172 (2023). https://doi.org/10.1007/s00432-022-04323-4

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