Research Paper Advance Articles

Identification and validation of oxeiptosis-associated lncRNAs and prognosis-related signature genes to predict the immune status in uterine corpus endometrial carcinoma

Linjun Niu1, , Zhengyuan Wu2, ,

  • 1 Department of Oncology, Huaibei People’s Hospital, Huaibei 235000, China
  • 2 Department of Hand Plastic Surgery, The First People’s Hospital of Linping District, Hangzhou 311199, China

Received: February 16, 2023       Accepted: May 3, 2023       Published: May 19, 2023      

https://doi.org/10.18632/aging.204726
How to Cite

Copyright: © 2023 Niu and Wu. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

As a novel cell death modality, oxeiptosis is mainly caused by oxidative stress. However, the associations of uterine corpus endometrial carcinoma (UCEC) with oxeiptosis-associated long non-coding RNAs (lncRNAs) are unknown. Here, to identify hub oxeiptosis-associated lncRNAs in UCEC, we collected the data for lncRNAs and gene expression in UCEC from The Cancer Genome Atlas (TCGA) database. Then, a lncRNA risk signature was constructed, and its prognostic value was further evaluated. Finally, the expression levels of hub lncRNA HOXB-AS3 were validated by quantitative RT-PCR analysis. MTT and wounding analyses were also applied to confirm the role of HOXB-AS3 knockdown on UCEC cells. Five lncRNAs associated with oxeiptosis and connected to the prognosis of UCEC were identified, and a risk signature was constructed based on these identified lncRNAs. Our clinical value analyses suggested that the risk signature was closely connected to the overall survival, TNM stage, and grade of UCEC patients. Meanwhile, compared to the conventional clinicopathological characteristics, this risk signature exhibited significantly higher diagnostic accuracy. Moreover, the potential mechanism analysis indicated a close connection of this risk signature to tumor stemness, m6A-related genes, immune cell infiltration, and immune subtypes. Based on the risk scores, we constructed a nomogram. In vitro experiments found that HOXB-AS3 was significantly higher expressed in UCEC cells, and the silence of HOXB-AS3 inhibited the proliferation and migration of UCEC cells. In conclusion, using five hub lncRNAs associated with oxeiptosis, we generated a risk signature, which could be applied in the novel therapeutic strategies of UCEC development.

Abbreviations

UCEC: uterine corpus endometrial carcinoma; PCD: programmed cell death; ACD: accident cell death; ROS: reactive oxygen species; lncRNAs: long non-coding RNAs; OS: overall survival; AJCC: American Joint Committee on Cancer; CSCs: cancer stem cell-like cells; TCGA: The Cancer Genome Atlas; UCSC: University of California Santa Cruz Xena; FDR: false discovery rate; FC: fold change; GSEA: Gene Set Enrichment Analysis.