PLOD2 high expression associates with immune infiltration and facilitates cancer progression in osteosarcoma

Zhen Wang; Gentao Fan; Hao Zhu; Lingfeng Yu; Diankun She; Yanting Wei; Jianhao Huang; Tianhang Li; Shoubin Zhan; Shenkai Zhou; Yan Zhu; Yicun Wang; Xi Chen; Jianning Zhao; Guangxin Zhou

doi:10.3389/fonc.2022.980390

PLOD2 high expression associates with immune infiltration and facilitates cancer progression in osteosarcoma

Front Oncol. 2022 Oct 5:12:980390. doi: 10.3389/fonc.2022.980390. eCollection 2022.

Authors

Zhen Wang¹, Gentao Fan¹, Hao Zhu², Lingfeng Yu³, Diankun She¹, Yanting Wei⁴, Jianhao Huang⁵, Tianhang Li⁶, Shoubin Zhan⁷, Shenkai Zhou⁷, Yan Zhu¹, Yicun Wang³, Xi Chen^{4

7}, Jianning Zhao¹, Guangxin Zhou¹

Affiliations

¹ Department of Orthopaedics, Jinling Hospital, Nanjing Medical University, Nanjing, China.
² Department of Orthopaedics, Affiliated Jianhu Hospital of Nantong University, Yancheng, China.
³ Department of Orthopaedics, Jinling Hospital, Nanjing University, Nanjing, China.
⁴ Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
⁵ Department of Orthopaedics, Jinling Hospital, Southern Medical University, Nanjing, China.
⁶ Department of Urology, Drum Tower Hospital, Nanjing University, Nanjing, China.
⁷ Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.

Abstract

Background: Osteosarcoma (OS) is the most common primary malignant bone tumors in children and adolescents. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) is a key gene in mediating the formation of the stabilized collagen cross-link, playing an important role in the progression of cancer. However, the interaction between OS and PLOD2 has not been clarified so far.

Methods: The target gene PLOD2 was screened through our own RNA-seq results and other two RNA-seq results from GEO database. The expression of PLOD2 in OS was detected by RT-qPCR, Western blot and immunohistochemistry. Functional experiments were performed to investigate the role of PLOD2 in OS cell invasion, migration and angiogenesis in vitro. An OS lung metastasis model was established to investigate the function of PLOD2 in OS metastasis and angiogenesis in vivo. The role of PLOD2 in immune infiltration in OS was explored by KEGG/GO analysis and immune infiltration analysis with TARGET, TCGA and TIMER.

Results: PLOD2 was high-expressed in OS, which was related to poor prognosis of OS patients. PLOD2 promoted OS cell migration, invasion and angiogenesis in vitro and aggravated OS metastasis and angiogenesis in vivo. Bioinformatic analysis showed that PLOD2 played an important role in immune cell infiltration in OS, including CD8 positive T cells, macrophages M0 cells, DC cells, endothelial cells, iDC cells, ly endothelial cells, MEP cells, mv endothelial cells, native B cells, smooth muscle cells and Th1 cells. Immunohistochemical results showed that the expression of CD4 and CD8A was negatively correlated with the expression of PLOD2 in OS.

Conclusion: PLOD2 was high-expressed in OS and promoted OS migration, invasion and angiogenesis in vitro and facilitated OS metastasis and angiogenesis in vivo. PLOD2 was associated with immune cell infiltration in OS, which could be a promising target to treat OS patients with metastasis and utilized to guide clinical immunotherapy in the future.

Keywords: PLOD2; angiogenesis; immune infiltration; invasion; migration; osteosarcoma.