Comprehensive Analysis of Fifteen Hub Genes to Identify a Promising Diagnostic Model, Regulated Networks, and Immune Cell Infiltration in Acute Kidney Injury

Overview

Journal J Clin Lab Anal

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
Pathology

Date 2022 Sep 20

PMID 36125921

Authors

Tao Sun

Ying Cao

Tiancha Huang

Yiwen Sang

Yibei Dai

Zhihua Tao

Affiliations

Soon will be listed here.

Abstract

Background: Acute kidney injury is a common clinical problem with no sensitive and specific diagnostic biomarkers and definitive treatments. The underlying molecular mechanisms of acute kidney injury are unclear. Therefore, it is pivotal to explore the underlying mechanisms and screen for novel diagnostic biomarkers, and therapeutic targets.

Methods: The present study identified 15 hub genes by WGCNA analysis. LASSO-based logistic regression analysis was used to select key features and construct a diagnostic model of AKI. In addition, GO and KEGG analyses were performed and TF-mRNA and miRNA-mRNA network analysis and immune infiltration analysis of hub genes were performed to reveal the underlying mechanisms of AKI.

Results: A diagnostic model was constructed by LASSO-based logistic regression analysis and was validated by RT-qPCR based on 15 hub genes. GO and KEGG analyses revealed DEGs were enriched in oxidation-reduction process, cell adhesion, proliferation, migration, and metabolic process. The enriched TFs were BRD2, EP300, ETS1, MYC, SPI1, and ZNF263. The enriched miRNAs were miR-181c-5p, miR-218-5p, miR-485-5p, miR-532-5p and miR-6884-5p. The immune infiltration analysis showed that Macrophages M2 was decreasing significantly revealing a protective factor for further AKI treatment.

Conclusions: The present study identified 15 hub genes based on WGCNA. Development and validation of a potentially diagnostic model based on 15 hub genes. In addition, exploring the interaction between transcriptional factors and 15 hub genes, and miRNA-mRNA relationship pairs. Furthermore, immune infiltration analysis was performed by analyzing gene expression profiles of AKI. Our study provides some basis for further experimental studies.

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References

Elgendy M, Fusco J, Segura V, Dolores Lozano M, Minucci S, Echeveste J . Identification of mutations associated with acquired resistance to sunitinib in renal cell cancer. Int J Cancer. 2019; 145(7):1991-2001. DOI: 10.1002/ijc.32256. View

Sun T, Wang D, Ping Y, Sang Y, Dai Y, Wang Y . Integrated profiling identifies SLC5A6 and MFAP2 as novel diagnostic and prognostic biomarkers in gastric cancer patients. Int J Oncol. 2020; 56(2):460-469. PMC: 6959404. DOI: 10.3892/ijo.2019.4944. View

Wang X, Liu J, Yin W, Abdi F, Pang P, Fucci Q . miR-218 Expressed in Endothelial Progenitor Cells Contributes to the Development and Repair of the Kidney Microvasculature. Am J Pathol. 2020; 190(3):642-659. PMC: 7068533. DOI: 10.1016/j.ajpath.2019.11.014. View

Zhang T, Xiang L . Honokiol alleviates sepsis-induced acute kidney injury in mice by targeting the miR-218-5p/heme oxygenase-1 signaling pathway. Cell Mol Biol Lett. 2019; 24:15. PMC: 6387556. DOI: 10.1186/s11658-019-0142-4. View

Schroeder J, Ibrahim H, Taylor L, Curthoys N . Role of deadenylation and AUF1 binding in the pH-responsive stabilization of glutaminase mRNA. Am J Physiol Renal Physiol. 2005; 290(3):F733-40. DOI: 10.1152/ajprenal.00250.2005. View

Venkatachalam M, Weinberg J, Kriz W, Bidani A . Failed Tubule Recovery, AKI-CKD Transition, and Kidney Disease Progression. J Am Soc Nephrol. 2015; 26(8):1765-76. PMC: 4520181. DOI: 10.1681/ASN.2015010006. View

Li X, Zheng P, Ji T, Tang B, Wang Y, Bai S . LINC00052 ameliorates acute kidney injury by sponging miR-532-3p and activating the Wnt signaling pathway. Aging (Albany NY). 2020; 13(1):340-350. PMC: 7835036. DOI: 10.18632/aging.104152. View

Yang Y, Markus M, Mangs A, Raitskin O, Sperling R, Morris B . ZRANB2 localizes to supraspliceosomes and influences the alternative splicing of multiple genes in the transcriptome. Mol Biol Rep. 2013; 40(9):5381-95. DOI: 10.1007/s11033-013-2637-9. View

Chawla L, Bellomo R, Bihorac A, Goldstein S, Siew E, Bagshaw S . Acute kidney disease and renal recovery: consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup. Nat Rev Nephrol. 2017; 13(4):241-257. DOI: 10.1038/nrneph.2017.2. View

10.

Liu D, Liu Y, Zheng X, Liu N . c-MYC-induced long noncoding RNA MEG3 aggravates kidney ischemia-reperfusion injury through activating mitophagy by upregulation of RTKN to trigger the Wnt/β-catenin pathway. Cell Death Dis. 2021; 12(2):191. PMC: 7892540. DOI: 10.1038/s41419-021-03466-5. View

11.

Wang N, Wu R, Tang D, Kang R . The BET family in immunity and disease. Signal Transduct Target Ther. 2021; 6(1):23. PMC: 7813845. DOI: 10.1038/s41392-020-00384-4. View

12.

Zhang Y, Zhao H, Su Q, Wang C, Chen H, Shen L . Novel Plasma Biomarker-Based Model for Predicting Acute Kidney Injury After Cardiac Surgery: A Case Control Study. Front Med (Lausanne). 2022; 8:799516. PMC: 8795513. DOI: 10.3389/fmed.2021.799516. View

13.

Chiba T, Peasley K, Cargill K, Maringer K, Bharathi S, Mukherjee E . Sirtuin 5 Regulates Proximal Tubule Fatty Acid Oxidation to Protect against AKI. J Am Soc Nephrol. 2019; 30(12):2384-2398. PMC: 6900790. DOI: 10.1681/ASN.2019020163. View

14.

Rocha M, Herance R, Rovira S, Hernandez-Mijares A, Victor V . Mitochondrial dysfunction and antioxidant therapy in sepsis. Infect Disord Drug Targets. 2012; 12(2):161-78. DOI: 10.2174/187152612800100189. View

15.

Kilari S, Sharma A, Zhao C, Singh A, Cai C, Simeon M . Identification of novel therapeutic targets for contrast induced acute kidney injury (CI-AKI): alpha blockers as a therapeutic strategy for CI-AKI. Transl Res. 2021; 235:32-47. PMC: 8328880. DOI: 10.1016/j.trsl.2021.03.005. View

16.

Klein S, Brandtner A, Lehner G, Ulmer H, Bagshaw S, Wiedermann C . Biomarkers for prediction of renal replacement therapy in acute kidney injury: a systematic review and meta-analysis. Intensive Care Med. 2018; 44(3):323-336. PMC: 5861176. DOI: 10.1007/s00134-018-5126-8. View

17.

Hublitz P, Kunowska N, Mayer U, Muller J, Heyne K, Yin N . NIR is a novel INHAT repressor that modulates the transcriptional activity of p53. Genes Dev. 2005; 19(23):2912-24. PMC: 1315397. DOI: 10.1101/gad.351205. View

18.

Perco P, Wilflingseder J, Bernthaler A, Wiesinger M, Rudnicki M, Wimmer B . Biomarker candidates for cardiovascular disease and bone metabolism disorders in chronic kidney disease: a systems biology perspective. J Cell Mol Med. 2008; 12(4):1177-87. PMC: 3865659. DOI: 10.1111/j.1582-4934.2008.00280.x. View

19.

Chen S, Wu P, Sun L, Zhou B, Niu W, Liu S . miR-204 regulates epithelial-mesenchymal transition by targeting SP1 in the tubular epithelial cells after acute kidney injury induced by ischemia-reperfusion. Oncol Rep. 2016; 37(2):1148-1158. DOI: 10.3892/or.2016.5294. View

20.

Liang W, Yamahara K, Hernando-Erhard C, Lagies S, Wanner N, Liang H . A reciprocal regulation of spermidine and autophagy in podocytes maintains the filtration barrier. Kidney Int. 2020; 98(6):1434-1448. DOI: 10.1016/j.kint.2020.06.016. View