Huang Liangkun, Zeng Xiaoshuang, Liang Wanting, Chen Junwen, Zhong Changheng, Cai Wenxiang, Wang Xuezhong, Zhu Zhengjie, Su Li, Liu Zilin, Peng Hao
Department of Orthopedics Surgery, Renmin Hospital of Wuhan University, Wuhan Hubei, 430060, China.
Department of Clinical Medicine, Xianyue Hospital of Xiamen Medical College, Xiamen, 310058, China.
Transl Oncol. 2023 Oct;36:101753. doi: 10.1016/j.tranon.2023.101753. Epub 2023 Aug 6.
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.
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.
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.
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.
乳酸代谢过程已被证明在多种癌症的进展中起关键作用，并影响免疫微环境，但其在骨肉瘤中的潜在作用仍不清楚。
我们从TARGET和GTEx数据库中获取了84例骨肉瘤样本和70例正常骨样本的转录组和临床数据。我们在骨肉瘤中鉴定出差异表达的乳酸代谢相关长链非编码RNA（LRLs），并进行Cox回归和LASSO回归以建立LRLs预后特征（LRPS）。通过单独的预后分析、生存曲线和受试者工作特征（ROC）曲线来检验LRPS性能的可靠性。此外，研究了LRPS对骨肉瘤免疫微环境的影响，并通过实验验证了关键基因的功能。
共鉴定出856个差异表达的LRLs，其中5个被选来构建LRPS，与其他已发表的预后特征相比，LRPS是骨肉瘤更好的预后预测指标（训练组和测试组的AUC分别高达0.947和0.839，KM曲线的adj-p<0.05）。我们发现LRPS显著影响骨肉瘤的免疫浸润，而RP11-472M19.2显著促进骨肉瘤的转移，这在实验中得到了很好的验证。令人鼓舞的是，为LRPS和RP11-472M19.2高危组鉴定出了一些敏感药物。
我们的研究表明，乳酸代谢在骨肉瘤的发展中起关键作用，并在实验中得到了很好的验证，为骨肉瘤的临床治疗和深入研究提供了极其重要的见解。
