一个新颖的内质网应激相关基因定义的风险特征签名,可用于预测卵巢癌的预后和免疫浸润状态。
A novel defined risk signature of endoplasmic reticulum stress-related genes for predicting the prognosis and immune infiltration status of ovarian cancer.
发表日期:2023 Jan 15
作者:
Jiahang Mo, Shunyi Ruan, Baicai Yang, Yunfeng Jin, Keyi Liu, Xukai Luo, Hua Jiang
来源:
Journal of Zhejiang University-SCIENCE B
摘要:
内质网应激(ER)是癌症的新兴标志特征之一,对细胞增殖、转移、侵袭和化疗耐药性有重大影响。由于诊断时间晚,卵巢癌(OvCa)是世界范围内癌症相关死亡的主要原因之一。近年来,研究探讨了ER对OvCa的影响,但ER相关基因在OvCa预后中的预测作用尚未被探究。在这里,我们从癌症基因组图谱(TCGA)和基因表达库(GEO)中筛选出552例涉及OvCa的ER应激相关基因,进行患者预后基因筛选。采用最小绝对收缩和选择算子(LASSO)回归,基于TCGA队列建立了ER应激相关风险签名。七个基因签名表现出良好的预测效能,适用于TCGA、国际癌症基因组联盟(ICGC)和另一个GEO队列(P<0.001,P<0.001和P = 0.04)。此外,功能注释表明,这个标记集富含细胞响应和衰老、细胞因子相互作用以及多种免疫相关术语。免疫浸润剖面进一步描绘出高风险组的免疫不响应状态。总之,ER应激相关基因是预测OvCa预后的重要因素,并具有临床应用潜力。
Endoplasmic reticulum (ER) stress, as an emerging hallmark feature of cancer, has a considerable impact on cell proliferation, metastasis, invasion, and chemotherapy resistance. Ovarian cancer (OvCa) is one of the leading causes of cancer-related mortality across the world due to the late stage of disease at diagnosis. Studies have explored the influence of ER stress on OvCa in recent years, while the predictive role of ER stress-related genes in OvCa prognosis remains unexplored. Here, we enrolled 552 cases of ER stress-related genes involved in OvCa from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts for the screening of prognosis-related genes. The least absolute shrinkage and selection operator (LASSO) regression was applied to establish an ER stress-related risk signature based on the TCGA cohort. A seven-gene signature revealed a favorable predictive efficacy for the TCGA, International Cancer Genome Consortium (ICGC), and another GEO cohort (P<0.001, P<0.001, and P=0.04, respectively). Moreover, functional annotation indicated that this signature was enriched in cellular response and senescence, cytokines interaction, as well as multiple immune-associated terms. The immune infiltration profiles further delineated an immunologic unresponsive status in the high-risk group. In conclusion, ER stress-related genes are vital factors predicting the prognosis of OvCa, and possess great application potential in the clinic.