Integrated analysis of single-cell and bulk RNA sequencing data reveals prognostic characteristics of lysosome-dependent cell death-related genes in osteosarcoma

作者全名：Wu, Yueshu; Yang, Jun; Xu, Gang; Chen, Xiaolin; Qu, Xiaochen

作者地址：[Wu, Yueshu; Yang, Jun; Xu, Gang; Qu, Xiaochen] Dalian Med Univ, Affiliated Hosp 1, Dept Orthopaed, Dalian, Peoples R China; [Wu, Yueshu; Yang, Jun; Xu, Gang; Qu, Xiaochen] Key Lab Mol Mech Repair & Remodeling Orthopaed Dis, Dalian 116011, Liaoning, Peoples R China; [Chen, Xiaolin] Chongqing Med Univ, Affiliated Hosp 2, Dept Orthoped Surg, 76 Linjiang Rd, Chongqing 400010, Peoples R China

通信作者：Qu, XC (通讯作者)，Dalian Med Univ, Affiliated Hosp 1, Dept Orthopaed, Dalian, Peoples R China.; Qu, XC (通讯作者)，Key Lab Mol Mech Repair & Remodeling Orthopaed Dis, Dalian 116011, Liaoning, Peoples R China.; Chen, XL (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Orthoped Surg, 76 Linjiang Rd, Chongqing 400010, Peoples R China.

来源：BMC GENOMICS

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001205159700001

JCR分区：Q2

影响因子：3.5

年份：2024

卷号：25

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Osteosarcoma; Lysosome-dependent cell death; Prognosis; Immune; Biomarkers

摘要：Background Tumor cells exhibit a heightened susceptibility to lysosomal-dependent cell death (LCD) compared to normal cells. However, the role of LCD-related genes (LCD-RGs) in Osteosarcoma (OS) remains unelucidated. This study aimed to elucidate the role of LCD-RGs and their mechanisms in OS using several existing OS related datasets, including TCGA-OS, GSE16088, GSE14359, GSE21257 and GSE162454.Results Analysis identified a total of 8,629 DEGs1, 2,777 DEGs2 and 21 intersection genes. Importantly, two biomarkers (ATP6V0D1 and HDAC6) linked to OS prognosis were identified to establish the prognostic model. Significant differences in risk scores for OS survival were observed between high and low-risk cohorts. Additionally, scores of dendritic cells (DC), immature DCs and gamma delta T cells differed significantly between the two risk cohorts. Cell annotations from GSE162454 encompassed eight types (myeloid cells, osteoblastic OS cells and plasma cells). ATP6V0D1 was found to be significantly over-expressed in myeloid cells and osteoclasts, while HDAC6 was under-expressed across all cell types. Moreover, single-cell trajectory mapping revealed that myeloid cells and osteoclasts differentiated first, underscoring their pivotal role in patients with OS. Furthermore, ATP6V0D1 expression progressively decreased with time.Conclusions A new prognostic model for OS, associated with LCD-RGs, was developed and validated, offering a fresh perspective for exploring the association between LCD and OS.

基金机构：National Natural Science Foundation of China

基金资助正文：Not applicable.