Identification of Ferroptosis-Related Long Noncoding RNA and Construction of a Novel Prognostic Signature for Gastric Cancer

Abstract

Background. Gastric cancer is the most common malignant tumor of the digestive system. It has a poor prognosis and is clinically challenging to treat. Ferroptosis is a newly defined mode of programmed cell death. The roles and prognostic value of ferroptosis-related long noncoding RNAs (lncRNAs) in gastric cancer remain unknown. Results. In the current study, 20 ferroptosis-related lncRNAs were identified via univariate Cox analysis, least absolute shrinkage, and selection operator Cox regression analysis and used to construct a prognostic signature and classify gastric cancer patients into high-risk and low-risk groups. The signature was validated using TCGA training and testing cohorts. The risk signature was an independent prognostic indicator of survival and accurately predicted the prognoses of patients with gastric cancer. It was also associated with immune cell infiltration. Gene set enrichment analysis was used to investigate underlying mechanisms that the 20 ferroptosis-related lncRNAs were involved in. Chemosensitivity and immune checkpoint inhibitor analyses indicated that high-risk patients were more sensitive to the immune checkpoint inhibitor programmed cell death protein 1. Conclusions. The important role of ferroptosis-related lncRNAs in immune infiltration identified in the current study may assist the determination of personalized prognoses and treatments in patients with gastric cancer. These 20 lncRNAs can be used as the diagnostic and prognostic markers for gastric cancer.

Application of apoptosis-related genes in a multiomics-related prognostic model study of gastric cancer

“…In the previous 2 years, there have been numerous studies on signatures associated with the prognosis of GC, such as hypoxia-immune-based gene signatures (Liu et al, 2020), long non-coding RNA signatures (Ghafouri-Fard and Taheri 2020), ferroptosis-related lncRNAs signatures (Chen et al, 2021a) and immune-related signatures (Zhao et al, 2021). Although escaping programmed cell death (apoptosis) is a hallmark of tumors (Hanahan and Weinberg 2000), there are no relevant studies on the prognosis of apoptosis-related signatures in GC.…”

Role of ferroptosis and ferroptosis-related non-coding RNAs in the occurrence and development of gastric cancer

“…The experiment of Wang et al confirmed that lncLASTR mediated the proliferation and migration of GC cells through the regulation of ferroptosis (Wang G. et al, 2022) (Pan et al, 2021). These ferroptosisrelated lncRNAs may play an important role in the immune infiltration of GC, which may help to determine the personalized prognosis and treatment of GC patients (Chen W. et al, 2021). Zhang et al also established a ferroptosis-related lncRNA model that could predict the prognosis of stomach adenocarcinoma patients .…”

“…Pan et al prognostic model based on the 17 ferroptosis-related lncRNAs may improve the overall survival prediction of GC ( Pan et al, 2021 ). These ferroptosis-related lncRNAs may play an important role in the immune infiltration of GC, which may help to determine the personalized prognosis and treatment of GC patients ( Chen W. et al, 2021 ). Zhang et al also established a ferroptosis-related lncRNA model that could predict the prognosis of stomach adenocarcinoma patients ( Zhang S. et al, 2022 ).…”

Cell death affecting the progression of gastric cancer

“… Programmed necrosis RNA AUC of ROC Ref. necroptosis 16 lncRNAs : LINC01829, LINC02657, RNF139-AS1, FRMD6-AS2, AGBL5-IT1, AC116914.1, AC005165.1, AL353804.2, AC004596.1, AL355574.1, AC012409.3, AC124067.4, AC015813.1, AP001189.3, AL133245.1, AC069549.1 0.770 [ 97 ] 12 lncRNAs : REPIN1-AS1, UBL7-AS1, LINC00460, LINC02773, CHROMR, LINC01094, FLNB-AS1, ITFG1-AS1, LASTR, PINK1-AS, LINC01638, PVT1 0.748 [ 98 ] pyroptotic 11 lncRNAs : AL353804.1, AC147067.2, AP001318.2, RRN3P2, UBL7-AS1, AC018752.1, ACTA2-AS1, AL121772.1, AC005332.4, HAGLR, AC245041.2 0.850 [ 99 ] ferroptosis 20 lncRNAs : AC114271.1, AC147067.2, AL353796.1, AC104958.1, AC087521.1, AL590705.3, AC068790.7, AC090772.1, LINC01094, AC007405.3, AC083902.1, LINC00460, AC005165.1, AC048382.2, AC106782.5, STX18-AS1, AL355574.1, CYMP-AS1, AC006547.1, LINC02696 0.947 [ 100 ] 17 lncRNAs : ENSG00000249835.2, ENSG0000023671 9.2, ENSG00000250241.4, ENSG00000240661.1, ENSG0000026 2061.4, ENSG00000229656.5, ENSG00000175746.6, ENSG00000 248599.1, ENSG00000254333.1, ENSG00000247134.5, and ENSG00000248362.1, ENSG00000234449.2, ENSG0000023 9513.4, ENSG00000265334.1, ENSG00000267201.1, ENSG 00000273293.1, ENSG00000230107.1 0.751 [ 101 ] 4 lncRNAs: AP003392.1, AC245041.2, AP001271.1, BOLA3-AS1 0.636 [ 102 ] 12 lncRNAs : AC026368.1, CFAP61-AS1, AC090772.1, LINC00449, AC005165.1, LINC01614, AL356215.1, REPIN1-AS1, LASTR, LINC00460, AC015712.1, PVT1. 0.734 [ 103 ] 6 lncRNAs : STX18-AS1, MIR99AHG, LINC01197, LINC00968, LINC00865, LEF1-AS1 0.640 [ 104 ] 3 lncRNAs : P000695.2, AL365181.3, LINC01615 0.670 [ 105 ] The bold values represent the number of lncRNAs in each gastric cancer prediction model.…”