Pan‐cancer analysis identifies the IRF family as a biomarker for survival prognosis and immunotherapy

Abstract IRF family genes have been shown to be crucial in tumorigenesis and tumour immunity. However, information about the role of IRF in the systematic assessment of pan‐cancer and in predicting the efficacy of tumour therapy is still unknown. In this work, we performed a systematic analysis of IRF family genes in 33 tumour samples, including expression profiles, genomics and clinical characteristics. We then applied Single‐Sample Gene‐Set Enrichment Analysis (ssGSEA) to calculate IRF‐scores and analysed the impact of IRF‐scores on tumour progression, immune infiltration and treatment efficacy. Our results showed that genomic alterations, including SNPs, CNVs and DNA methylation, can lead to dysregulation of IRFs expression in tumours and participate in regulating multiple tumorigenesis. IRF‐score expression differed significantly between 12 normal and tumour samples and the impact on tumour prognosis and immune infiltration depended on tumour type. IRF expression was correlated to drug sensitivity and to the expression of immune checkpoints and immune cell infiltration, suggesting that dysregulation of IRF family expression may be a critical factor affecting tumour drug response. Our study comprehensively characterizes the genomic and clinical profile of IRFs in pan‐cancer and highlights their reliability and potential value as predictive markers of oncology drug efficacy. This may provide new ideas for future personalized oncology treatment.


Figure S1
Figure S1 Flowchart of this work.Figure S2 Expression and survival profiles of IRFs in pan-cancer.Figure S3 Single nucleotide variation (SNV) frequency, CNV and methylation of IRFs. Figure S4 Survival and clinical analysis of IRF-score in pan-cancer.Figure S5 Pathway and immuno-infiltration analysis of IRF scores in pan-cancer.Figure S6 ssGSEA and Cibersort analysis of IRF scores in pan-cancer.Figure S7 Correlation between IRFscore and drug sensitivity and TMB.Figure S8 Correlation between IRF-score and immune checkpoints and tumour stem cells.

Figure S2
Figure S1 Flowchart of this work.Figure S2 Expression and survival profiles of IRFs in pan-cancer.Figure S3 Single nucleotide variation (SNV) frequency, CNV and methylation of IRFs. Figure S4 Survival and clinical analysis of IRF-score in pan-cancer.Figure S5 Pathway and immuno-infiltration analysis of IRF scores in pan-cancer.Figure S6 ssGSEA and Cibersort analysis of IRF scores in pan-cancer.Figure S7 Correlation between IRFscore and drug sensitivity and TMB.Figure S8 Correlation between IRF-score and immune checkpoints and tumour stem cells.

Figure S3
Figure S1 Flowchart of this work.Figure S2 Expression and survival profiles of IRFs in pan-cancer.Figure S3 Single nucleotide variation (SNV) frequency, CNV and methylation of IRFs. Figure S4 Survival and clinical analysis of IRF-score in pan-cancer.Figure S5 Pathway and immuno-infiltration analysis of IRF scores in pan-cancer.Figure S6 ssGSEA and Cibersort analysis of IRF scores in pan-cancer.Figure S7 Correlation between IRFscore and drug sensitivity and TMB.Figure S8 Correlation between IRF-score and immune checkpoints and tumour stem cells.
Figure S1 Flowchart of this work.Figure S2 Expression and survival profiles of IRFs in pan-cancer.Figure S3 Single nucleotide variation (SNV) frequency, CNV and methylation of IRFs. Figure S4 Survival and clinical analysis of IRF-score in pan-cancer.Figure S5 Pathway and immuno-infiltration analysis of IRF scores in pan-cancer.Figure S6 ssGSEA and Cibersort analysis of IRF scores in pan-cancer.Figure S7 Correlation between IRFscore and drug sensitivity and TMB.Figure S8 Correlation between IRF-score and immune checkpoints and tumour stem cells.

Figure S1
Figure S1 Flowchart of this work.

Figure S2
Figure S2 Expression and survival profiles of IRFs in pan-cancer.A-B.Heat map of IRF family gene expression signatures in GTEx (A) and CCLE (B) dataset.C-E.Survival analysis of IRF, including disease-specific survival (C), disease free survival (D) and progression free survival (E).

Figure S3
Figure S3 Single nucleotide variation (SNV) frequency, CNV and methylation of IRFs. A. Frequency of mutations in the IRF family.The numbers represent the number of samples with the corresponding mutated IRF in respective tumors.B. Correlation of CNV with mRNA expression.(Person correlation coefficient).The size of the dots represents statistical significance.C. Correlation of methylation with mRNA expression.The size and colour of the dots represent correlation.Orange represents negative correlation; blue represents positive correlation.

Figure S4
Figure S4 Survival and clinical analysis of IRF-score in pan-cancer. A. Kaplan-Meier analysis of survival differences in IRF-score in pan-cancer.B. Scatter plot of the distribution of DSS, DFS and PFS with IRF score in LUAD and UCEC patients.C. Boxplots of IRF-score between different characteristics in pan-cancer patients, including patient age, stage, grade, T and M.

Figure S5
Figure S5 Pathway and immuno-infiltration analysis of IRF scores in pan-cancer. A. Infiltration abundance of each pathway score (ssGSEA) in two IRF scoring groups in pan-cancer.B. Results of ESTIMATE calculations in two IRF score groups in pan-cancer, including stromal score, immune score and estimate score.

Figure
Figure S6 ssGSEA and Cibersort analysis of IRF scores in pan-cancer. A. Infiltration abundance of each immune cell in two IRF scoring groups in pan-cancer(ssGSEA).B-L.Ratio of infiltration of each immune cell in both IRF scoring groups in pan-cancer (Cibersort).

Figure S7
Figure S7 Correlation between IRFscore and drug sensitivity and TMB. A. Alluvial plots show the sensitivity distribution of different drugs in pan-cancer in two subgroups.B. Kaplan-Meier curves for high and low TMB groups in pan-cancer.C. Kaplan-Meier curves for patients stratified by TMB and ICI scores in pan-cancer.

Figure S8
Figure S8 Correlation between IRF-score and immune checkpoints and tumor stem cells.A. Heat map of the correlation between IRF-score and immune checkpoints.B. Differences in DNAss distribution among high and low IRF score groups in pan-cancer.C. Differences in RNAss distribution among high and low IRF score groups in pan-cancer.