Dissecting the role of lactate metabolism LncRNAs in the progression and immune microenvironment of osteosarcoma

Abstract

Background: The process of lactate metabolism has been proved to play a critical role in the progression of various cancers and to influence the immune microenvironment, but its potential role in osteosarcoma remains unclear. Methods: We have acquired transcriptomic and clinical data from 84 osteosarcoma samples and 70 normal bone samples from the TARGET and GTEx databases. We identified differentially expressed lactate metabolism-related LncRNAs (LRLs) in osteosarcoma and performed Cox regression and LASSO regression to establish LRLs prognostic signature (LRPS). The reliability of LRPS performance was examined by separate prognostic analysis, viability curves and receiver operating characteristic (ROC) curves. Furthermore, the effects of LRPS on the immune microenvironment of osteosarcoma were investigated, and the functions of the focal genes were experimentally validated. Result: A total of 856 differentially expressed LRLs were identified and 5 of them were selected to construct LRPS, which was a better prognostic predictor for osteosarcoma compared with other published prognostic signatures (AUC up to 0.947 and 0.839 in the training and test groups, respectively, with adj-p<0.05 for KM curves). We found that LRPS significantly affected the immune infiltration of osteosarcoma, while RP11-472M19.2 significantly promoted the metastasis of osteosarcoma, which was well validated experimentally. Encouragingly, a number of sensitive drugs were identified for LRPS and RP11-472M19.2 high-risk groups. Conclusion: Our study shows that lactate metabolism plays a crucial role in the development of osteosarcoma and has been well validated experimentally, providing extremely important insights into the clinical treatment and in-depth research of osteosarcoma.

Keywords

• osteosarcoma
• metastasis
• lactate metabolism
• long non-coding RNA
• prognosis
• Immune infiltration