Table 1.

Bioinformatic studies predicting prognosis of patients based on the expression of ferroptosis-related genes and non-coding RNAs.

Dataset used in the study	Low-risk	High-risk	Highlights of the study	Ref.
TCGA, GSE68465, and GSE72094	TLR4, PHKG2, PEBP1, GLS2, FLT3, and ALOX15	VDAC2, PGD, PANX1, KRAS, ALOX12B, ACSL3, CISD1, FANCD2, and SLC3A2	* “The expression of KRAS and PGD was positively related to tumor mutation burden, indicating that KRAS and PGD could serve as novel biomarkers for predicting immunotherapy response rate” * “VDAC2, GLS2, FLT3, TLR4, PGD, PANX1, PEBP1, ACSL3, CISD1, FANCD2, and SLC3A2 were of statistical significance” * “The four ferroptosis suppressor genes, ACSL3, CISD1, FANCD2, and SLC3A2, increased the tumor’s stem cell-like features and were all positively associated with CD133 and CD44” * “Ferroptosis process involves the development of tumor immune evasion (e.g., IL-17 signaling pathway).” * “PEBP1 could be a promising treatment target and is positively related to chemotherapy sensitivity.”	(81)
TCGA and GSE68465	ALOX15, IL33, and GDF15	DDIT4 and HNF4A	* “Ferroptosis-related gene signatures can be used as a potential predictor for the prognosis of LUAD.” * “TCGA cohort showed lower scores in immune-related cells, such as mast cells, neutrophils, dendritic cells (DCs), and T helper cells, with only natural killer (NK) cells showing higher scores.” * “The high-risk group in the two cohorts showed lower scores for type II and type I IFN responses.”	(82)
TCGA, GSE72094, and GSE68465	NCOA4, GLS2, ALOX15, PEBP1, and PHKG2	ACSL3, PGD, ATP5G3, CISD1, and ALOX12B	* “The enriched gene sets in the high-risk group were mainly involved in pathways related to glycolysis, mTORC1, MYC, G2/M checkpoint, unfolded protein response, E2F, hypoxia, mitotic spindle assembly, epithelial-mesenchymal transition, and late response to estrogen.” * “Resting mast cells and resting dendritic cells can be identified as having a potential prognostic capacity in LUAD.” * “A total of 62.85% (308/490) of autophagy-related genes were found to be significantly correlated with risk scores.”	(83)
TCGA, GSE72094, and GPL15048	ANGPTL7, SLC1A4, GDF15, DUOX1, PHKG2, CDO1, LINC00472, DPP4, LINC00336, ALOX15, and GLS2	TXNRD1, DDIT4, SLC7A5, SLC2A1, RRM2, AURKA, ALOXE3, SLC7A11, and GCLC	* “The relationship between the ferroptosis-related genes and tumor-infiltrating immune cells was revealed by ANGPTL7 and M2 macrophages, ANGPTL7 and monocytes, GDF15 and M1 macrophages, LINC00472 and M2 macrophages, RRM2 and M1 macrophages, RRM2 and monocytes, and SLC2A1 and M1 macrophages.”	(84)
TCGA, GSE11969, GSE13213, GSE30219, GSE31210, and GSE41271	DUOX1, ALOX15, DPP4, CDO1, GDF15, and IL33	SLC7A11, GCLC, FANCD2, HELLS, ALOX12B, ALOXE3, TXNRD1, SRXN1, GPX2, DDIT4, SLC7A5, SLC2A1, RRM2, and AURKA	* “ALOX12B, ALOX15, GPX2, DDIT4, and GDF15 were increased and SLC2A1 and were decreased after erastin treatment.” * “ALOX15 was significantly low expressed in Ki67-high samples, while GPX2, DDIT4, and SLC2A1 were high expressed in Ki67-high samples.” * “Down-regulation of either GPX2 or DDIT4 could partially reverse the cell proliferation arrest.” * “Significantly enriched KEGG pathways include cell cycle, complement, and coagulation cascades, p53 signaling, cellular senescence, and fatty acid metabolism.”	(85)
TCGA, GSE72094, and GSE30219	AGER, ALOX15B, DPP4, GLS2, ISCU, PEBP1, PHKG2, SLC11A2,	ATP5MC3, CISD1, EGLN1, FANCD2, ITGA6, ITGB4, KRAS, NEDD4, SLC38A1, SLC7A5, STYK1, TFAP2A, VDAC1 AND VDAC2	* “Top five pathways enriched in the high-risk group were the cell cycle, ubiquitin-mediated proteolysis, oocyte meiosis, homologous recombination and p53 signaling.” * “The top five pathways enriched in the low-risk group were the arachidonic acid metabolism, primary bile acid biosynthesis, alpha-linolenic acid metabolism, asthma, and intestinal immune network for IgA production pathways.” * “Pathways of the immune response were significantly enriched in the 15-gene ferroptosis signature.”	(86)
TCGA	ALOX15, and PEBP1	ACSL4, GSS, ACSL3 and PGD	* “Gene’s mutation frequencies were higher in the high-risk group [TP53 (53%), TTN (50%), MUC16 (42%), CSMD3 (40%), and RYR2 (39%)].” * “The mainly enriched pathways included the neuroactive ligand-receptor interaction, metabolism of xenobiotics by cytochrome P450, steroid hormone biosynthesis, staphylococcus aureus infection pathway, IL-17 signaling pathway, retinol metabolic pathway.”	(87)
GSE68465, GSE41271, and GPL6884	CYBB and SAT2	CISD1, FADD and VDAC2	* “Several immune-related pathways were enriched in low-risk group, such as B cell receptor signaling pathway, T cell receptor signaling pathway, Intestinal immune network for IgA production, NOD line receptor signaling pathway, Fc epsilon Ri signaling pathway, Fc gamma R signaling pathway, and Graft versus host disease.” * “GSEA analysis showed the FRGS was highly associated with immune status. The enrichment score of aDCs, DCs, iDCs, pDCs, B cells, Macrophages, Mast cells, Neutrophils, T helper cells, Th1 cells, TIL and Treg was significantly increased in low-risk group. Meanwhile, low-risk group had a higher score of C–C chemokine receptor (CCR), the activity of checkpoint molecules, HLA, T cell co−stimulation and IFN Response Type II.”	(88)
TCGA GSE3141, GSE30219, and GSE31210	NOX1 and ALOX15	GSS, ACSL4, CISD1, SLC3A2, and FANCD2	* “Overall, the 12 top-ranked with highest mutations genes were shared between both sets KEAP1, NAV3, and FAT3, were expressed only in the high-risk group, while COL11A1, CSMD1, and ZNF536 were specifically expressed in the low-risk group.” * “The enrichment results revealed that processes related to poor survival in lung cancer patients, cancer microenvironment, immature B lymphocytes, early T lymphocytes and lung metastasis were significantly enriched in the high-risk group while processes related to COMP, lectin, TCRA, NOTCH1 target and hypoxia were significantly enriched in the low-risk group.” * “Ferroptosis-related risk score (FRRS) is involved in several immune-signaling pathways.” * “The gene expression levels of potential immunotherapy targets, including CD276, PD-L1, and NKG2A, were significantly upregulated in the high-risk group. Meanwhile, the expression levels of VSIR and CD27 were significantly higher in the low-risk group than in the high-risk group.” * “The top three genes that contributed most to FRRS were CISD1, FANCD2 and SLC3A2. The results illustrated that low CISD1 expression was significantly associated with favorable immunotherapeutic responses”	(89)
TCGA, GSE13213, and GSE72904	ALOX15, and DPP4	FANCD4, GCLC, and SLC7A11	* “Differentially expressed genes (DEGs) were mostly enriched in the ferroptosis pathway and immune-related pathways, such as human T-cell leukemia virus 1 (HTLV-1) infection pathway. These findings suggested that there exists crosslinking between ferroptosis and tumor immunity in NSCLC.” * “The GSE13213 dataset revealed differences in the scores of HLA class and type-I and -II immune interferon response.” * “The immune score of the subgroups in both TCGA cohort and the GSE13213 dataset was significantly different, especially the score of macrophages and mast cells.”	(90)
TCGA, GSE72094, and GSE68465	ARNTL, GLS2, HERPUD1, LPIN1, NCOA4, PEBP1, and TLR4	ACSL3, CISD1, DDIT4, EIF2S1, PANX1, RELA, RRM2, and YWAHE	* “ACSL3, YWHAE, DDIT4, PANX1, RELA, CISD1, EIF2S1, and RRM2 were overexpressed, while GLS2, PEBP1, ARNTL, NCOA4, LPIN1, HERPUD1, and TLR4 were downregulated in high-risk groups.” * “GAPDH, BIRC5, ERO1L, EIF2S1, SPHK1, ATIC, GNAI3, NAMPT, EIF4EBP1, and FADD are the top 10 autophagy-related genes that positively corrected with the risk score; 8/10 showed a significant elevated hazard ratio in LUAD.” * “ERN1, ATG16L2, CCR2, IKBKB, HSPB8, PRKCD, DAPK1, DRAM1, DLC1, and DAPK2 are the leading 10 that have negative relationships with the 15-gene signature risk score; three of them exhibited a decreased hazard ratio.” * “Enriched gene sets of HALLMARK collection in the high-risk group were mainly involved in pathways related to glycolysis, unfolded protein response, mTORC1, MYC, G2/M checkpoint, E2F, DNA repair, mitotic spindle assembly, ultraviolet radiation, hypoxia, cholesterol homeostasis, and reactive oxygen species, whereas the gene set concerned with metabolism of bile acids and salts was primary enriched in the low-risk group.”	(91)
TCGA	PEBP1, DPP4, ALOX15, GLS2, NCOA4 and PHKG2	ACSL3, GSS, PGD, FANCD2, SLC7A11, GCLC, CISD1, and ATP5MC3	* “PEBP1, ACSL3, NCOA4, PHKG2, and CISD1 were independent prognostic factors for overall survival.” * “Four kinds of immune cells showed higher infiltration levels in the high-risk group, including CD4 memory-activated T cells, M0 macrophages, M1 macrophages and activated dendritic cells, and three kinds of immune cells showed higher infiltration levels in the low-risk group, including resting mast cells, activated mast cells and eosinophils.” * “The results showed that the high-risk group had higher immune and stromal scores than those of the low-risk group.” * “PEBP1, CISD1 and NCOA4 were significantly down-regulated in the LUAD tissues.”	(92)
TCGA and GSE31210	ALOX15, DPP4, GLS2, PHKG2, and PEBP1	ATP5MC3, CISD1, FANCD2, GCLC, SLC7A11, ACSL3, ABCC1, and PGD	* “The higher risk group was significantly associated with higher tumor stage, TP53 mutation, sex, and advanced tumor node metastasis (TNM) stage in the TCGA cohort” * “Four immune‐related biological processes or molecular functions in KEGG were changed between the high‐ and low‐risk groups in the TCGA cohort, including the intestinal immune network for IGA production, chemokine signaling pathway, TGF beta signaling pathway, and TOLL‐like receptor signaling pathway” * “Four immune‐related biological processes or molecular functions in KEGG were changed between the high‐ and low‐risk groups in the TCGA cohort, including the intestinal immune network for IGA production, chemokine signaling pathway, TGF beta signaling pathway, and TOLL‐like receptor signaling pathway” * “Six immune‐related biological processes or molecular functions in GO were changed between the high‐ and low‐risk groups in the TCGA cohort, including somatic diversification of immune receptors, positive regulation of production of molecular, positive regulation of myeloid leukocyte cytokines, positive regulation of cytokine production, regulation of innate immune response, and activation of the innate immune response” * “The score of CD8+ T cells, iDCs, macrophages, mast cells, NK cells, Th1 cells, Th2 cells, Treg, antigen‐presenting cells (APC) coi-nhibition, cytolytic activity, HLA, inflammation‐promoting, MHC class I, para-inflammation, and T cell co-inhibition were significantly different between the low‐ and high‐risk groups in both TCGA”	(93)
TCGA	AC026355.1, AC124045.1, and AC025048.4	LINC01843, MIR193BHG, AC124045.1, AC091185.1, AC027031.2, ALO21707.2, ALO31667.3, and AL606834.1	* “lncRNA AL031667.3 increased with age, AC027031.2 was abundantly expressed in female patients, the expression of AC091185.1 and AC124045.1 was associated with TNM stage, that of AC091185.1, AC124045.1, AL021707.2, and LINC01843 was associated with pT stage, and that of AC124045.1, AL021707.2, AL031667.3, and MIR193BHG was associated with pN stage. Patients with decreased AC124045.1 expression were more likely to have distant metastases”	(94)
TCGA and GSE37745	CRNDE, AC106047.1, AC090559.1, AL691432.2, AC026355.1, AL034397.3, AC087752.3, VIM-AS1, HLA-DQB1-AS1, AC092171.5, LINCO0996, AC123595.1, ACO011477.2, and HSPC324	AL606489.1, LINC02081, AP000695.2, LINC01843, FAM83A-AS1, AP000695.1, and AC010980.2,	* “The Gene Ontology (GO) terms activation of innate immune response, innate immune response activating signal transduction, positive regulation of innate immune response, interleukin 1 mediated signaling pathway, and regulation of apoptotic signaling pathway were enriched in LUAD samples with high-risk scores. In contrast, CD8+ alpha beta T cell activation, T cell-mediated immunity, MAST cell-mediated immunity, regulation of leukocyte-mediated immunity, and regulation of lymphocyte-mediated immunity were enriched in LUAD samples with low-risk scores.” * “KEGG pathways were identified. Cell cycle, pancreatic cancer, p53 signaling pathway, pathogenic Escherichia coli, and small cell lung cancer signaling pathways were enriched in the high-risk group. Several immune response pathways, such as the intestinal immune network for IgA production, FC epsilon RI signaling pathway, autoimmune thyroid disease, allograft rejection, and graft versus host disease, were enriched in the low-risk group.”	(95)
TCGA, GSE3141, and GSE37745	ARHGEF26-AS1 C20orf197 MGC32805 LINC00324	LINC01116, LINC01137, and TMPO-AS1	* “The correlation expression between 7 lncRNAs and four most common ferroptosis-related mRNAs (FTH1, GPX4, ACSL4, PTGS2) verified the relationship between 7 lncRNAs and ferroptosis from another perspective.” * “Comparative analysis of immune cells and pathways confirmed the differences of HLA, MHC class I, para-inflammation, type I IFN response, type II IFN response, B cell, iDCs, mast cell, neutrophils, NK cell, T helper cell and TIL between two risk groups.”	(96)
TCGA, GSE30219, GES31210, and GSE31546	C5orf64, LINC01800, LINC00968, LINC01352, and PGM5-AS1	LINC02097, DEPDC1-AS1, WWC2-AS2, SATB2-AS1, LINC00628, LINC01537, and LMO7DN	* “The KEGG analysis results show that the 12 prognostic lncRNAs are mainly enriched in DNA replication pathway, B cell receptor signaling pathways, hematopoietic cell lineage pathway, and cell cycle pathway”	(97)