Exploring the impact of insufficient thermal ablation on hepatocellular carcinoma: NDST2 overexpression mechanism and its role in facilitating growth and invasion of residual cancer cells

Abstract

Objective

Incomplete thermal ablation (ITA) fosters the malignancy of residual cells in Hepatocellular carcinoma (HCC) with unclear mechanisms now. This study aims to investigate the expression changes of NDST2 following ITA of HCC and its impact on residual cancer cells.

Methods

An in vitro model of heat stress-induced liver cancer was constructed to measure the expression of NDST2 using Quantitative Real-Time PCR and Western blotting experiments. The sequencing data from nude mice were used for validation. The clinical significance of NDST2 in HCC was evaluated by integrating datasets. Gene ontology and pathway analysis were conducted to explore the potential signaling pathways regulated by NDST2. Additionally, NDST2 was knocked down in heat stress-induced HCC cells, and the effects of NDST2 on these cells were verified using Cell Counting Kit-8 assays, scratch assays, and Transwell assays.

Results

NDST2 expression levels are elevated in HCC, leading to a decrease in overall survival rates of HCC patients. Upregulation of immune checkpoint levels in high NDST2-expressing HCC may contribute to immune evasion by liver cancer cells. Additionally, the low mutation rate of NDST2 in HCC suggests a relatively stable expression of NDST2 in this disease. Importantly, animal and cell models treated with ITA demonstrate upregulated expression of NDST2. Knockdown of NDST2 in heat stress-induced liver cancer cells results in growth inhibition associated with gene downregulation.

Conclusion

The upregulation of NDST2 can accelerate the progression of residual HCC after ITA, suggesting a potential role for NDST2 in the therapeutic efficacy and prognosis of residual HCC.

Keywords:

• Hepatocellular carcinoma
• NDST2
• incomplete thermal ablation
• residual cancer
• tumor-suppressive

Acknowledgements

Thanks to Key Laboratory of Ultrasonic Molecular Imaging and Artificial Intelligence, Guangxi Zhuang Autonomous Region Engineering Research Center for Artificial Intelligence Analysis of Multimodal Tumor Images, Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, and Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education for their support of this study. We thank Home for Researchers editorial team (www.home-for-researchers.com) for language editing service.

Ethics approval and consent to participate

Animal experiment in this study was approved by the ethics committee of The First Affiliated Hospital of Guangxi Medical University (NO.2019-KY-(084)). All experiments were performed in accordance with ARRIVE guidelines and relevant regulations.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

TCGA dataset (https://portal.gdc.com), ArrayExpress dataset (https://www.ebi.ac.uk/arrayexpress/), GEO dataset (https://www.ncbi.nlm.nih.gov/geo/) and STRING database (http://www.string-db.org/) were used in the study. The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. And the Nude Mice sequencing datasets generated and analyzed during the current study are available in the GEO repository (record GSE234283). The following secure token has been created to allow review of record GSE234283 while it remains in private status: cvebmegybtgdvqr.

Additional information

Funding

This study was funded by the Clinical Research Climbing Project of The First Affiliated Hospital of Guangxi Medical University (No. YYZS2020024), the National Natural Science Foundation of China (No. 81960329, 82160350, 82160336), and the Natural Science Foundation of Guangxi (2020GXNSFDA238005).