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

Wang,Min; Min,Min; Mai,Jia; Liu,Xiaojuan

doi:10.3892/ol.2024.14531

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

Authors:
- Min Wang
- Min Min
- Jia Mai
- Xiaojuan Liu
View Affiliations

Affiliations: Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China, Outpatient Department, The Air Force Hospital of Western Theater, People's Liberation Army, Chengdu, Sichuan 500643, P.R. China
Published online on: June 26, 2024 https://doi.org/10.3892/ol.2024.14531
Article Number: 398
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

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.

View Figures

View References

1	Owens B: Kidney cancer. Nature. 537:S972016. View Article : Google Scholar : PubMed/NCBI
2	Linehan WM, Schmidt LS, Crooks DR, Wei D, Srinivasan R, Lang M and Ricketts CJ: The metabolic basis of kidney cancer. Cancer Discov. 9:1006–1021. 2019. View Article : Google Scholar : PubMed/NCBI
3	Ricketts CJ, De Cubas AA, Fan H, Smith CC, Lang M, Reznik E, Bowlby R, Gibb EA, Akbani R, Beroukhim R, et al: The cancer genome atlas comprehensive molecular characterization of renal cell carcinoma. Cell Rep. 23:313–326.e315. 2018. View Article : Google Scholar : PubMed/NCBI
4	Turajlic S, Swanton C and Boshoff C: Kidney cancer: The next decade. J Exp Med. 215:2477–2479. 2018. View Article : Google Scholar : PubMed/NCBI
5	Latif F, Tory K, Gnarra J, Yao M, Duh FM, Orcutt ML, Stackhouse T, Kuzmin I, Modi W and Geil L: Identification of the von Hippel-Lindau disease tumor suppressor gene. Science. 260:1317–1320. 1993. View Article : Google Scholar : PubMed/NCBI
6	Zhang Y, Qin P, Tian L, Yan J and Zhou Y: The role of mediator complex subunit 19 in human diseases. Exp Biol Med (Maywood). 246:1681–1687. 2021. View Article : Google Scholar : PubMed/NCBI
7	Napoli C, Schiano C and Soricelli A: Increasing evidence of pathogenic role of the mediator (MED) complex in the development of cardiovascular diseases. Biochimie. 165:1–8. 2019. View Article : Google Scholar : PubMed/NCBI
8	Chadick JZ and Asturias FJ: Structure of eukaryotic Mediator complexes. Trends Biochem Sci. 30:264–271. 2005. View Article : Google Scholar : PubMed/NCBI
9	Singh N and Han M: sur-2, a novel gene, functions late in the let-60 ras-mediated signaling pathway during Caenorhabditis elegans vulval induction. Gene Dev. 9:2251–2265. 1995. View Article : Google Scholar : PubMed/NCBI
10	Grants JM, Goh GY and Taubert S: The mediator complex of caenorhabditis elegans: Insights into the developmental and physiological roles of a conserved transcriptional coregulator. Nucl Acids Res. 43:2442–2453. 2015. View Article : Google Scholar : PubMed/NCBI
11	Bourbon HM: Comparative genomics supports a deep evolutionary origin for the large, four-module transcriptional mediator complex. Nucleic Acids Res. 36:3993–4008. 2008. View Article : Google Scholar : PubMed/NCBI
12	Koschubs T, Seizl M, Larivière L, Kurth F, Baumli S, Martin DE and Cramer P: Identification, structure, and functional requirement of the Mediator submodule Med7N/31. EMBO J. 28:69–80. 2009. View Article : Google Scholar : PubMed/NCBI
13	Zhang X, Gao D, Fang K, Guo Z and Li L: Med19 is targeted by miR-101-3p/miR-422a and promotes breast cancer progression by regulating the EGFR/MEK/ERK signaling pathway. Cancer Lett. 444:105–115. 2019. View Article : Google Scholar : PubMed/NCBI
14	Mehine M, Mäkinen N, Heinonen HR, Aaltonen LA and Vahteristo P: Genomics of uterine leiomyomas: Insights from high-throughput sequencing. Fertil Steril. 102:621–629. 2014. View Article : Google Scholar : PubMed/NCBI
15	Zhu LJ, Yan WX, Chen ZW, Chen Y, Chen D, Zhang TH and Liao GQ: Disruption of mediator complex subunit 19 (Med19) inhibits cell growth and migration in tongue cancer. World J Surg Oncol. 11:1162013. View Article : Google Scholar : PubMed/NCBI
16	Joseph C, Macnamara O, Craze M, Russell R, Provenzano E, Nolan CC, Diez-Rodriguez M, Sonbul SN, Aleskandarany MA, Green AR, et al: Mediator complex (MED) 7: A biomarker associated with good prognosis in invasive breast cancer, especially ER+ luminal subtypes. Br J Cancer. 118:1142–1151. 2018. View Article : Google Scholar : PubMed/NCBI
17	Chen ZL, Ma YY, Mou XZ and Zhang JG: Upregulation of MED7 was associated with progression in hepatocellular carcinoma. Cancer Biomark. 38:603–611. 2023. View Article : Google Scholar : PubMed/NCBI
18	Tan W, Peng S, Li Z, Zhang R, Xiao Y, Chen X, Zhu J, Li B and Lv X: Identification of therapeutic targets and prognostic biomarkers among genes from the mediator complex family in the hepatocellular carcinoma tumour-immune microenvironment. Comput Math Methods Med. 2022:20216132022. View Article : Google Scholar : PubMed/NCBI
19	Sato S, Tomomori-Sato C, Tsai KL, Yu X, Sardiu M, Saraf A, Washburn MP, Florens L, Asturias FJ, Conaway RC and Conaway JW: Role for the MED21-MED7 hinge in assembly of the mediator-RNA polymerase II holoenzyme. J Biol Chem. 291:26886–26898. 2016. View Article : Google Scholar : PubMed/NCBI
20	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
21	Steven A and Seliger B: The role of immune escape and immune cell infiltration in breast cancer. Breast care (Basel). 13:16–21. 2018. View Article : Google Scholar : PubMed/NCBI
22	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2018. CA Cancer J Clin. 68:7–30. 2018. View Article : Google Scholar : PubMed/NCBI
23	Shuch B, Amin A, Armstrong AJ, Eble JN, Ficarra V, Lopez-Beltran A, Martignoni G, Rini BI and Kutikov A: Understanding pathologic variants of renal cell carcinoma: Distilling therapeutic opportunities from biologic complexity. Eur Urol. 67:85–97. 2015. View Article : Google Scholar : PubMed/NCBI
24	Goyal R, Gersbach E, Yang XJ and Rohan SM: Differential diagnosis of renal tumors with clear cytoplasm: Clinical relevance of renal tumor subclassification in the era of targeted therapies and personalized medicine. Arch Pathol and Lab Med. 137:467–480. 2013. View Article : Google Scholar : PubMed/NCBI
25	Choueiri TK and Motzer RJ: Systemic therapy for metastatic renal-cell carcinoma. N Eng J Med. 376:354–366. 2017. View Article : Google Scholar : PubMed/NCBI
26	Quail DF and Joyce JA: Microenvironmental regulation of tumor progression and metastasis. Nat Med. 19:1423–1437. 2013. View Article : Google Scholar : PubMed/NCBI
27	Coussens LM, Zitvogel L and Palucka AK: Neutralizing tumor-promoting chronic inflammation: A magic bullet? Science. 339:286–291. 2013. View Article : Google Scholar : PubMed/NCBI
28	Yu W, Zhang Z, Min D, Yang Q, Du X, Tang L, Lin F, Sun Y, Zhao H, Zheng S, et al: Mediator of RNA polymerase II transcription subunit 19 promotes osteosarcoma growth and metastasis and associates with prognosis. Eur J Cancer. 50:1125–1136. 2014. View Article : Google Scholar : PubMed/NCBI
29	Huang S, Hölzel M, Knijnenburg T, Schlicker A, Roepman P, McDermott U, Garnett M, Grernrum W, Sun C, Prahallad A, et al: MED12 controls the response to multiple cancer drugs through regulation of TGF-β receptor signaling. Cell. 151:937–950. 2012. View Article : Google Scholar : PubMed/NCBI
30	Zhou Y, Tan Y, Zhang Q, Duan Q and Chen J: MED12 mutation as a potential predictive biomarker for immune checkpoint inhibitors in pan-cancer. Eur J Med Re. 27:2252022. View Article : Google Scholar
31	Zhang Y and Zhang Z: The history and advances in cancer immunotherapy: Understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications. Cell Mol Immunol. 17:807–821. 2020. View Article : Google Scholar : PubMed/NCBI
32	Robinson PJ, Trnka MJ, Pellarin R, Greenberg CH, Bushnell DA, Davis R, Burlingame AL, Sali A and Kornberg RD: Molecular architecture of the yeast mediator complex. eLife. 4:e087192015. View Article : Google Scholar : PubMed/NCBI