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. 2024 Jun 26;28(2):398.
doi: 10.3892/ol.2024.14531. eCollection 2024 Aug.

Systematic analysis of the expression profiles and prognostic significance of the MED gene family in renal clear cell carcinoma

Min Wang  1   2 , Min Min  3 , Jia Mai  1   2 , Xiaojuan Liu  1   2
Affiliations

Systematic analysis of the expression profiles and prognostic significance of the MED gene family in renal clear cell carcinoma

Min Wang et al. Oncol Lett. .

Abstract

The mediator complex (MED) family is a contributing factor in the regulation of transcription and proliferation of cells, and is closely associated with the development of various types of cancer. However, the significance of the expression levels and prognostic value of MED genes in kidney renal clear cell carcinoma (KIRC) have rarely been reported. The present study analyzed the expression and prognostic potential of MED genes in KIRC. The Search Tool for the Retrieval of Interacting Genes/Proteins was used to construct the protein-protein interaction network (PPI), the Assistant for Clinical Bioinformatics database was used to perform correlation analysis, GEPIA 2 was utilized to draw the Kaplan-Meier plot and analyze prognostic significance and the Tumor Immune Estimation Resource was used to assess the association of MED genes with the infiltration of immune cells in patients with KIRC. A total of 30 MED genes were identified, and among these genes, 11 were selected for the creation of a prognostic gene signature based on the results of a LASSO Cox regression analysis. Furthermore, according to univariate and multivariate analyses, MED7, MED16, MED21, MED25 and MED29 may be valuable independent predictive biomarkers for the prognosis of individuals with KIRC. Furthermore, there were significant differences in the expression levels of MED7, MED21 and MED25 in KIRC among different tumor grades. Additionally, patients with KIRC with high transcription levels of MED7, MED21 and MED29 had considerably longer overall survival times. The expression levels of MED genes were also linked to the infiltration of several immune cells. Overall, MED genes may have potential significance in predicting the prognosis of patients with KIRC.

Keywords: MED gene family; bioinformatics analysis; renal clear cell carcinoma.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1.
Figure 1.
Correlation analysis of the MED gene family, and its associated pathways and molecular functions. (A) Protein-protein interaction network of the MED gene family. (B) Correlations between 30 MED genes with each other. (C) GO BPs of the MED gene family. (D) GO CCs of the MED gene family. BP, biological process; CC, cellular component; GO, Gene Ontology; MED, mediator complex.
Figure 2.
Figure 2.
Patients with kidney renal clear cell carcinoma were divided into different molecular types in accordance with the MED gene family. (A) CDF curve. Different clusters are distinguished by different colors. (B) Consensus clustering based on δ area curve. (C) Heatmap of sample clustering at consensus k=3. (D) Gene expression heatmap of significant prognostic genes in C1, C2 and C3 subtypes. The gene expression level varies from −2 to 2, with red denoting high expression and blue denoting low expression. (E) Survival curves of different cluster groups. CDF, cumulative distribution function; MED, mediator complex.
Figure 3.
Figure 3.
Construction and validation of an 11-gene signature in patients with kidney renal clear cell carcinoma. (A) Altering trajectory of different independent variables. To find the hub genes, the least absolute shrinkage and selection operator regression methods were applied. (B) Confidence interval under each λ. (C) Distribution of risk scores, summary of survival, and heatmap of the 11 genes in the high-risk group and low-risk group. (D) Survival curve distribution of the 11-gene signature in the two groups (P=1.95×10−12). (E) Time-dependent receiver operating characteristic curve for 1-, 3- and 5-year survival prediction. AUC, area under the curve; MED, mediator complex.
Figure 4.
Figure 4.
Clinical prognostic value of a five-gene signature in patients KIRC. (A) Univariate and (B) multivariate Cox analyses of the MED family genes in TCGA-KIRC cohort. (C) Nomogram prediction for 1-, 2-, 3- and 5-year overall survival of patients with KIRC. (D) 1-, 2-, 3- and 5-year calibration curves of the nomogram. KIRC, kidney renal clear cell carcinoma; MED, mediator complex; TCGA, The Cancer Genome Atlas; TNM, tumor-node-metastasis.
Figure 5.
Figure 5.
Prognostic feature of the mRNA expression levels of MED genes in patients with KIRC. (A) Kaplan-Meier curves of overall survival for the five MED family genes in patients with KIRC. (B) mRNA expression in patients with KIRC between tumor and normal tissues. (C) mRNA expression in patients with KIRC among different tumor grades. KIRC, kidney renal clear cell carcinoma; MED, mediator complex; TCGA, The Cancer Genome Atlas. *P<0.05, **P<0.01, ***P<0.001.
Figure 6.
Figure 6.
Relationships between MED genes and tumor-infiltrating immune cells in kidney renal clear cell carcinoma. (A) MED7. (B) MED16. (C) MED21. (D) MED25. (E) MED29. MED, mediator complex.
Figure 7.
Figure 7.
Verification of the relationship between two MED genes and KIRC by immunohistochemistry analysis. (A) Clinicopathological information of 10 patients with KIRC. N and T kidney tissue was obtained from all 10 patients. (B) Expression levels of MED7 and MED21 in N and T kidney tissue (magnification, ×40). KIRC, kidney renal clear cell carcinoma; MED, mediator complex; N, normal; T, tumor.
Figure 8.
Figure 8.
Verification of the relationship between two MED genes and kidney renal clear cell carcinoma by siRNA-induced knockdown. (A) Reverse transcription-quantitative PCR was used to verify the knockdown efficiency. The data are presented as the mean ± SD. (B) Migration of 786-o cells with MED7 and MED21 knockdown was assessed using an uncoated Transwell assay (48 h) (magnification, ×20). (C) Migration of 786-o cells after MED7 and MED21 knockdown was measured using a wound healing assay (24 h) (magnification, ×10). MED, mediator complex; UNC, universal negative control; siRNA, small interfering RNA.
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Grants and funding

The present study was supported by the National Natural Science Foundation of China (grant no. 82301923) and the crosstalk task of Sichuan University (grant nos. 19H0125, 23H0221 and 23H0222).