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Ferroptosis-related long non-coding RNA signature predicts the prognosis of lung adenocarcinoma
- Citation Author(s):
- Submitted by:
- zhu li
- Last updated:
- Tue, 06/18/2024 - 07:43
- DOI:
- 10.21227/f3qp-a635
- License:
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Abstract
Studies indicate the occurrence and development of lung adenocarcinoma (LUAD) is regulated by ferroptosis and long non-coding RNA (lncRNA). While the role of ferroptosis-related lncRNA signature on the prognosis of LUAD is unclear. This study aimed to identify ferroptosis-related lncRNA signature for predicting the prognosis of LUAD. RNA expression profile and clinical data of LUAD patients were downloaded from public databases. The cox regression model was used to construct a multi-lncRNA signature. A total of 13 differentially expressed ferroptosis-related lncRNAs were significantly associated with the prognosis of LUAD. Kaplan-Meier survival curve analysis showed that patients in the high-risk group had a worse prognosis than those in the low-risk group. In addition, the area under the time-dependent receiver operating characteristic curve of 13 lncRNAs signature for predicting LUAD was 0.728. Gene set enrichment analysis suggested immune and tumor-related pathways were mainly concentrated in the low-risk group. Furthermore, immune functions such as T cell-cosuppression, T cell-costimulation, type I interferon response, and type II interferon response between the low-risk group and the high-risk group were significantly different. In conclusion, we identified a new ferroptosis-related lncRNA signature for predicting the prognosis of LUAD. Targeted ferroptosis may be a therapeutic option for LUAD.
Lung cancer is one of the most harmful malignant tumors in human health and life. According to the global cancer statistics in 2022, there were 2,480,301 newly diagnosed lung cancer cases which accounted for 12.4% of global cancer and over 1,817,172 patients died from this disease approximately (1). Lung adenocarcinoma (LUAD) is a common type of non-small cell lung cancer, which is relatively prone to metastasis(2). Most LUAD is diagnosed at an intermediate to advanced stage and only about 25% of patients are suitable for surgery(3). Patients with LUAD have a high risk of recurrence and metastasis even after surgery. However, it is difficult to make LUAD prognosis prediction for the complexity of etiologic factors and the high heterogeneity(4). In addition, limited by therapeutic strategies for LUAD, new prognostic signature needs to be developed.
Ferroptosis is a new type of cell death, which is independent of caspase activity and receptor-interacting protein 1 (RIPK1) kinase activity(5). Abnormal iron metabolism disorders can increase the risk of tumors and promote tumor growth. Tumor cells are more dependent on ferroptosis deposition than normal cells(6). In recent years, ferroptosis inducers have emerged as a potential therapeutic option to trigger cancer cell death, especially in malignant tumors that are resistant to conventional therapy(7). Apart from ferroptosis inducer, numerous lncRNAs have been identified as regulators or signature of ferroptosis.
Long non-coding RNA (lncRNA) is an RNA molecule with a length between 200-100000 nt. The accumulating studies showed that lncRNA not only participated in biological processes such as tumor genesis and development, but also played a vital role in regulation of cell cycle(8) and cell differentiation(9){Bhan, 2017 #413}{Bhan, 2017 #413}. LncRNA GABPB1-AS1 and GABPB1 performed an important role in regulating oxidative stress during the ferroptosis of HepG2 hepatocellular carcinoma cells induced by erastin. In addition, the high expression of GABPB1 was associated with poor prognosis in hepatocellular carcinoma patients(10). Further study revealed that Alox-dependent ferroptosis participated in pulmonary infection(11). However, whether ferroptosis-related lncRNA is associated with the prognosis of LUAD remains unclear.
Therefore, this study constructed a new ferroptosis-related lncRNA signature for predicting the prognosis of LUAD based on TCGA. The function of ferroptosis-related genes, N6-methyladenosine mRNA status, and different immune responses in the prognosis of LUAD were also validated so as to provide new insights into the accurate diagnosis and precise treatment of LUAD.
