Low NT5DC2 expression predicts favorable prognosis and suppresses soft tissue sarcoma progression via ECM-receptor interaction pathway

Zhen Huang; Enjie Xu; Xiaolong Ma; Yongjie Wang; Jiazhuang Zhu; Kunpeng Zhu; Jianping Hu; Chunlin Zhang

doi:10.1016/j.tranon.2024.101937

Low NT5DC2 expression predicts favorable prognosis and suppresses soft tissue sarcoma progression via ECM-receptor interaction pathway

Transl Oncol. 2024 Jun:44:101937. doi: 10.1016/j.tranon.2024.101937. Epub 2024 Mar 27.

Authors

Zhen Huang¹, Enjie Xu¹, Xiaolong Ma¹, Yongjie Wang¹, Jiazhuang Zhu¹, Kunpeng Zhu¹, Jianping Hu¹, Chunlin Zhang²

Affiliations

¹ Department of Orthopaedic, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
² Department of Orthopaedic, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200092, China. Electronic address: shzhangchunlin123@163.com.

Abstract

Background: Soft tissue sarcoma, a malignant tumor arising from mesenchymal tissues with poor prognosis. 5'-Nucleotidase Domain Containing 2 (NT5DC2) is a novel oncogene, and the precise involvement of NT5DC2 in soft tissue sarcoma were still undefined. Hence, our study aims to investigate NT5DC2 functions in soft tissue sarcoma progression.

Methods: The tumor immune single-cell hub 2 (TISCH2) website, The Cancer Genome Atlas (TCGA) pan-cancer or sarcoma and Gene Expression Omnibus (GEO, GSE21122) databases were applied to visualize the NT5DC2 status in the sarcoma databases. The NT5DC2 protein expression in sarcoma tissues in our hospital was detected by using immunohistochemistry (IHC) and analyzed the associations between NT5DC2 expression and clinicopathological parameters. Real-time quantitative polymerase chain reaction (RT-qPCR), colony formation, 5-ethynyl-2'-deoxyuridine (EdU) assay, wound healing, transwell, flow cytometry and xenograft model were used to elucidate the effects of NT5DC2 downregulated by lentivirus in sarcoma cell.

Results: The TISCH2 website detection found that NT5DC2 expression is enriched in malignant cells in sarcoma single-cell database. Furthermore, the TCGA-sarcoma database indicated that NT5DC2 expression correlates with metastasis, positive margin status, prognosis, and diagnostic value. Additionally, IHC staining showed that 40 % of soft tissue sarcoma patients present high expression of NT5DC2, and NT5DC2 upregulation is closely associated with poor prognosis. Functional verification analysis further revealed that downregulating NT5DC2 expression can suppress sarcoma progression through the ECM-receptor interaction pathway.

Conclusion: Low expression of NT5DC2 predicts a favorable prognosis in soft tissue sarcoma, and downregulated NT5DC2 expression can suppress sarcoma cell progression through the ECM-receptor interaction pathway.

Keywords: ECM-receptor interaction pathway; NT5DC2; Prognosis; Progression; Soft tissue sarcoma.