Basic Study
Copyright ©The Author(s) 2023.
World J Gastrointest Oncol. Oct 15, 2023; 15(10): 1717-1738
Published online Oct 15, 2023. doi: 10.4251/wjgo.v15.i10.1717
Figure 1
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Figure 1 Workflow of this study. APCs: Antigen-presenting cells; CNV: Copy number variation; HCC: Hepatocellular carcinoma; ICGC: International Cancer Genome Consortium; ICPs: Immune checkpoints; ICDs: Immune cell death modulators; TCGA: The Cancer Genome Atlas; WGVNA: Weighted gene coexpression network analysis.
Figure 2
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Figure 2 Screening of candidate tumor antigen genes in hepatocellular carcinoma. A: Chromosome distribution of differentially expressed genes; B: Overlapping samples in altered genome fraction groups; C: Overlapping samples in mutation count groups; D: Genes with the highest frequency in altered genome fraction groups; E: Genes with the highest frequency in mutation count groups.
Figure 3
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Figure 3 Identification of tumor antigens associated with hepatocellular carcinoma prognosis. A: Venn diagram of mutated genes, amplified genes, highly expressed genes, and prognostic genes; B-N: Kaplan-Meier curves showing that high expression of AURKA (B), CCNB1 (C), CDC25C (D), CDK1 (E), KIF2C (F), KPNA2 (G), MCM3 (H), NEK2 (I), PES1 (J), PPM1G (K), PRC1 (L), PTTG1 (M), and TRIP13 (N) indicates a worse overall survival in hepatocellular carcinoma patients. AMP: Amplification; HR: Hazard ratio; RFS: Recurrence-free survival.
Figure 4
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Figure 4 Identification of immune subtypes of hepatocellular carcinoma. A: Cumulative distribution function curve of immune-related genes in the The Cancer Genome Atlas (TCGA) cohort; B: Delta area of immune-related genes in the TCGA cohort; C: Sample clustering heatmap in the TCGA cohort; D: Kaplan-Meier curves showing the overall survival of the hepatocellular carcinoma immune subtypes in the TCGA cohort; E: Cumulative distribution function curve of immune-related genes in the International Cancer Genome Consortium (ICGC) cohort; F: Delta area of immune-related genes in the ICGC cohort; G: Sample clustering heatmap in the ICGC cohort; H: Kaplan-Meier curves showing the overall survival of the hepatocellular carcinoma immune subtypes in the ICGC cohort. CDF: Cumulative Distribution Function.
Figure 5
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Figure 5 Clinicopathological characteristics of immune subtypes of hepatocellular carcinoma. A and B: Complex heatmap of clinicopathological characteristics of immune subtypes of hepatocellular carcinoma (HCC) patients in the The Cancer Genome Atlas (TCGA) (A) and International Cancer Genome Consortium (ICGC) (B) cohorts; C and D: Distribution of immune subtypes across HCC pStage in the TCGA (C) and ICGC (D) cohorts.
Figure 6
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Figure 6 Mutational landscape of distinct immune subtypes. A: Mutational landscape oncoplot of the top 20 mutated genes in the hepatocellular carcinoma (HCC) immune subtypes; B to D: Tumor mutational burden (B), mutation number (C), and altered genome fractions (D) in HCC IS1-IS4. aP value < 0.05; bP value < 0.01; cP value < 0.001; TMB: Tumor mutational burden; NS: Not significant.
Figure 7
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Figure 7 Immune microenvironment characteristics of immune subtypes. A to C: Estimate scores (A), immune scores (B), and stromal scores (C) of hepatocellular carcinoma (HCC) immune subtypes in The Cancer Genome Atlas (TCGA) cohort; D to F: Estimate scores (D), immune scores (E), and stromal scores (F) of HCC immune subtypes in International Cancer Genome Consortium (ICGC) cohort; G and H: Heatmap of enrichment scores of 28 immune cell signatures among HCC immune subtypes in the (G) TCGA and (H) ICGC cohorts. aP value < 0.05; bP value < 0.01; cP value < 0.001; NS: Not significant.
Figure 8
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Figure 8 Association between immune subtypes and immune checkpoint/immune cell death modulator-related genes. A and B: Box plot of differential expression of immune checkpoint genes among immune subtypes in the The Cancer Genome Atlas (TCGA) (A) and International Cancer Genome Consortium (ICGC) (B) cohorts; C and D: Box plot of differential expression of immune cell death modulator genes among immune subtypes in the TCGA (C) and ICGC (D) cohorts. aP value < 0.05; bP value < 0.01; cP value < 0.001; dP value < 0.0001; NS: Not significant.
Figure 9
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Figure 9 Identification of potential biomarkers for mRNA vaccines. A: Differential distribution of module eigengenes among distinct hepatocellular carcinoma immune subtypes; B: Heatmap of module trait relationships; C: Dot plot showing the top 10 GO terms in the yellow module; D: Dot plot showing the top 10 KEGG terms in the yellow module; E and F: Kaplan-Meier plots showing overall survival (E) and recurrence-free survival (F) of the yellow module prognostic gene expression score; G: Distribution of six previously reported pancancer immune subtypes among IS1-IS4. dP value < 0.0001; NS: Not significant; HR: Hazard ratio.