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一种新型的内质网应激相关基因风险特征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.

机构信息

Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China.

Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China.

出版信息

J Zhejiang Univ Sci B. 2023 Jan 15;24(1):64-77. doi: 10.1631/jzus.B2200272.

Abstract

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 (<0.001, <0.001, and =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.

摘要

内质网应激作为癌症的一个新兴特征标志,对细胞增殖、转移、侵袭和化疗耐药性有很大影响。卵巢癌(OvCa)是全球癌症相关死亡率的主要原因之一,因为在诊断时疾病已经处于晚期。近年来,研究已经探讨了内质网应激对 OvCa 的影响,而内质网应激相关基因在 OvCa 预后中的预测作用仍未得到探索。在这里,我们从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)中招募了 552 例涉及 OvCa 的内质网应激相关基因病例,用于筛选预后相关基因。最小绝对收缩和选择算子(LASSO)回归被应用于基于 TCGA 队列建立内质网应激相关风险特征。一个由七个基因组成的特征揭示了该特征在 TCGA、国际癌症基因组联合会(ICGC)和另一个 GEO 队列中的良好预测效果(<0.001、<0.001 和 =0.04,分别)。此外,功能注释表明,该特征富集在细胞反应和衰老、细胞因子相互作用以及多种免疫相关术语中。免疫浸润图谱进一步描绘了高危组中免疫无反应状态。总之,内质网应激相关基因是预测 OvCa 预后的重要因素,在临床中有很大的应用潜力。

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