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. 2022 Sep 26;15(1):204.
doi: 10.1186/s12920-022-01339-0.

A pyroptosis-associated signature plays a role in prognosis prediction in clear cell renal cell carcinoma

Zhiyuan Li  1 , Zhinan Xia  1 , Yipeng Yu  1 , Licheng Cai  1 , Wengang Jian  1 , Tengda Wang  1 , Wei Xue  1 , Xingyuan Wang  1 , Bowen Wang  1 , Peng Zhang  1 , Wenhao Yao  1 , Cheng Zhang  2   3 , Chunyang Wang  4
Affiliations

A pyroptosis-associated signature plays a role in prognosis prediction in clear cell renal cell carcinoma

Zhiyuan Li et al. BMC Med Genomics. .

Abstract

Background: Approximately 90% of renal malignancies are RCCs (renal cell carcinomas), and the primary subtype in histology is ccRCC (clear cell RCC). In recent years, pyroptosis has been considered a kind of inflammation-related programmed cell death that participates in the invasion, metastasis, and proliferation of tumour cells, thereby influencing tumour prognosis. Nonetheless, the expression level of pyroptosis-associated genes in RCCs and their relationship with prognosis remain obscure.

Results: In our research, 44 regulators of pyroptosis that were differentially expressed between normal kidney and ccRCC tissues were identified. ccRCC cases were categorized into 2 subgroups according to prognostic-related DEGs (differentially expressed genes), and there was a significant difference in OS (overall survival) between them. The prognostic value of pyroptosis-associated genes was assessed as a signature based on a cohort from TCGA (The Cancer Genome Atlas). Following Cox regression with DEGs and LASSO (least absolute shrinkage and selection operator), a 6-gene signature was established, and all ccRCC cases in the cohort from TCGA were categorized into an LR (low-risk) or HR (high-risk) group (P < 0.001). In combination with clinical features, risk scores were considered a predictive factor of OS in ccRCC. KEGG (Kyoto Encyclopedia of Genes and Genomes) and GO (Gene Ontology) analyses suggest increased immunity and enrichment of genes related to immunity in the HR group.

Conclusions: Our findings indicate that genes related to pyroptosis have an important role in tumour immunity and may be used to predict the prognosis of ccRCC.

Keywords: Bioinformatics analysis; Clear cell renal cell carcinoma; Functional enrichment analysis; Immune infiltration; Multiomics data; Prognosis; Pyroptosis.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Expressions and interactions of 44 pyroptosis-linked genes. A Heatmap (blue: low level of expression; red: high level of expression) of genes linked to pyroptosis between tumour (T, brilliant red) and normal (N, brilliant blue) tissues. ***P < 0.001, **P < 0.01, *P < 0.05. B Interaction between genes linked to pyroptosis indicated by the PPI network (the interaction score was 0.9). C Hub genes ranked by node number. D The correlation network of genes related to pyroptosis (blue colour, negative; red colour, positive), whereby the depth of colour represents the relative strength
Fig. 2
Fig. 2
Tumour categorization according to PRGs related to prognosis. A Total of 539 ccRCC patients were assigned into 2 clusters based on the CCA matrix (k = 2; High expression level cluster of prognostic PRGs, C1; Low expression level cluster of prognostic PRGs; C2). B The clinicopathologic features and heatmap of the 2 clusters categorized by PRGs (T, N, and M classification included lymph node metastasis, tumour size, and distant metastasis) (P values: *P < 0.05; **P < 0.01; ***P < 0.001). C Kaplan–Meier OS curves for the 2 clusters
Fig. 3
Fig. 3
Risk signatures were constructed using the cohort from TCGA. A ccRCC was analysed by univariate Cox regression for every DEG linked to pyroptosis and 8 genes with P less than 0.05. B Six genes linked to OS were analysed by LASSO regression. C The selection of parameters was cross-validated. D Case distribution according to the RS. E Principal component analysis for ccRCCs according to the RS. F Survival of every patient (the right side of the dark line, HR cases; the left side, LR cases). G KM curves for ccRCC cases in the LR group and HR group. H Predictive efficiency of the RS indicated by ROC curves
Fig. 4
Fig. 4
The RS was analysed by Cox regression. A Kaplan–Meier analysis of the six hub genes linked to pyroptosis (ELANE, AIM2, GSDMB, IL6, NLRP1, and NOD2) in TCGA. B Results of univariate analysis of the cohort from TCGA. C Results of multivariate analysis the cohort from TCGA. D Heatmap (blue colour, downregulated expression; red colour, upregulated expression) of relationships of clinical characteristics with risk groups (***P < 0.001, **P < 0.01, *P < 0.05)
Fig. 5
Fig. 5
Analyses of functional enrichment. A Bubble graph showing GO enrichment. B Bubble graph of KEGG enrichment (more dark red indicates more notable differences, and larger bubbles indicate more genes enriched; MF, molecular function; CC, cellular component; BP, biological process; q-value: adjusted p value)
Fig. 6
Fig. 6
Infiltration levels of immune cells with the six PRG mutants were linked to prognosis. A AIM2, B ELANE, C GSDMB, D IL6, E NLRP1, F NOD2. ***P < 0.001, **P < 0.01, *P < 0.05(navy blue, Deep Deletion; light blue, Arm-level Deletion; grey, Diploid/Normal; yellow, Arm-level Gain; red, High Amplication; P-value refers to the correlation between different mutants and normal group)
Fig. 7
Fig. 7
Correlation of risk scores with immune infiltration levels in ccRCC. The risk score of the PRG prognostic model correlated positively with infiltration levels of immune cells .A B cells, B CD4+ T cells, C CD8+ T cells, D dendritic cells, E neutrophils, F macrophages. (Cor > 0, P < 0.05)
Fig. 8
Fig. 8
Correlation of six hub genes with immune infiltration levels in ccRCC. (Types of immune cells include CD8+ T cells, B cells, CD4+ T cells, dendritic cells, neutrophils, and macrophages.) |Cor|> 0, P < 0.05 was considered significant
Fig. 9
Fig. 9
ssGSEA scores concerning immune pathways and cells. A Enrichment scores of sixteen types of immune cells between the LR group (blue box) and HR group (red box). B Enrichment scores of thirteen pathways linked to immunity between the high-risk (red box) and low-risk (blue box) groups. ***P < 0.001, **P < 0.01, *P < 0.05
Fig. 10
Fig. 10
Specific data analysis workflow diagram
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