A novel prognostic signature in osteosarcoma characterised from the perspective of unfolded protein response

作者：Chengcheng Shi, Faming Zhao, Tingting Zhang, Denghui Xu, Zhuang-Yu Hao, Fengzhen Cui, Jihua Shi, Yang Jin, Ningning Li, Caihong Yang, Yi Zhang, Xia Sheng · 发表于：Clinical and Translational Medicine · 年份：2022 · DOI：10.1002/ctm2.750 · 被引用次数：19 · 研究领域：Endoplasmic Reticulum Stress and Disease、Autophagy in Disease and Therapy、Bioinformatics and Genomic Networks

Osteosarcoma (OS) is the most common primary malignant tumour of bone with variable molecular biology and prognosis. This makes better patient stratification and precision treatment an urgent clinical need.1 Activation of the unfolded protein response (UPR) is a hallmark of cancer cells facing endoplasmic reticulum (ER) stress,2, 3 yet its clinical relevance in OS remains to be explored. By comprehensive interrogation of OS datasets established by us and others,4-7 the present study consolidates UPR activation as a critical molecular feature of OS and refines a prognostic gene signature from this perspective with translational potential. In this study (see Figure S1A for workflow), we assembled 5 independent OS cohorts (GSE99671, GSE126209, GSE21257, TARGET and Zhengzhou datasets), plus the TCGA sarcoma dataset. Three datasets (GSE99671, GSE126209 and Zhengzhou) with paired tumour and normal tissues were analysed for deregulated genes; two of them with relatively large sample size were further selected for pathway enrichment. Three datasets (GSE21257, TARGET and TCGA) with solely tumours and survival information for patient classification and prognostic model construction (Table S1). We first interrogated GSE99671 with paired tumour and normal samples, and identified 1581 differentially expressed genes (DEGs) [|log2 (fold change)| > .5 and adjust p value < .05] (Figure S1B). To our interest, several pathways related to ER function, such as response to ER stress and protein pr...