Zhao Jie, Zhao Rixiang, Wei Xiaocen, Jiang Xiaojing, Su Fan
Oncology Department, Laixi People's Hospital of Shandong Province, Qingdao, China.
Evid Based Complement Alternat Med. 2021 Oct 8;2021:1586312. doi: 10.1155/2021/1586312. eCollection 2021.
Ovarian cancer (OC) is the top of the aggressive malignancies in females with a poor survival rate. However, the roles of immune-related pseudogenes (irPseus) in the immune infiltration of OC and the impact on overall survival (OS) have not been adequately studied. Therefore, this study aims to identify a novel model constructed by irPseus to predict OS in OC and to determine its significance in immunotherapy and chemotherapy.
In this study, with the use of The Cancer Genome Atlas (TCGA) combined with Genotype-Tissue Expression (GTEx), 55 differentially expressed irPseus (DEirPseus) were identified. Then, we constructed 10 irPseus pairs with the help of univariate, Lasso, and multivariate Cox regression analysis. The prognostic performance of the model was determined and measured by the Kaplan-Meier curve, a time-dependent receiver operating characteristic (ROC) curve.
After dividing OC subjects into high- and low-risk subgroups via the cut-off point, it was revealed that subjects in the high-risk group had a shorter OS. The multivariate Cox regression performed between the model and multiple clinicopathological variables revealed that the model could effectively and independently predict the prognosis of OC. The prognostic model characterized infiltration by various kinds of immune cells and demonstrated the immunotherapy response of subjects with cytotoxic lymphocyte antigen 4 (CTLA4), anti-programmed death-1 (PD-1), and anti-PD-ligand 1 (PD-L1) therapy. A high risk score was related to a higher inhibitory concentration (IC) for etoposide (=0.0099) and mitomycin C (=0.0013).
It was the first study to identify a novel signature developed by DEirPseus pairs and verify the role in predicting OS, immune infiltrates, immunotherapy, and chemosensitivity. The irPseus are vital factors predicting the prognosis of OC and could act as a novel potential treatment target.
卵巢癌（OC）是女性侵袭性恶性肿瘤之首，生存率较低。然而，免疫相关假基因（irPseus）在OC免疫浸润中的作用以及对总生存期（OS）的影响尚未得到充分研究。因此，本研究旨在识别一种由irPseus构建的新型模型，以预测OC患者的OS，并确定其在免疫治疗和化疗中的意义。
在本研究中，利用癌症基因组图谱（TCGA）结合基因型-组织表达（GTEx），鉴定出55个差异表达的irPseus（DEirPseus）。然后，借助单变量、套索和多变量Cox回归分析，构建了10对irPseus。通过Kaplan-Meier曲线、时间依赖性受试者工作特征（ROC）曲线确定并衡量模型的预后性能。
通过切点将OC受试者分为高风险和低风险亚组后发现，高风险组受试者的OS较短。在模型与多个临床病理变量之间进行的多变量Cox回归显示，该模型能够有效且独立地预测OC的预后。该预后模型表征了各种免疫细胞的浸润情况，并展示了细胞毒性淋巴细胞抗原4（CTLA4）、抗程序性死亡1（PD-1）和抗PD配体1（PD-L1）治疗受试者的免疫治疗反应。高风险评分与依托泊苷（=0.0099）和丝裂霉素C（=0.0013）的较高抑制浓度（IC）相关。
这是第一项识别由DEirPseus对开发的新型特征并验证其在预测OS、免疫浸润、免疫治疗和化疗敏感性方面作用的研究。irPseus是预测OC预后的关键因素，并可作为一种新的潜在治疗靶点。
