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IMR Press / FBL / Volume 26 / Issue 11 / DOI: 10.52586/5018
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Open Access Article
Identification of candidate biomarker EMP3 and its prognostic potential in clear cell renal cell carcinoma
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1 Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022 Wuhan, Hubei, China
2 Institute of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022 Wuhan, Hubei, China
3 Department of Pathogenic Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430022 Wuhan, Hubei, China

These authors contributed equally.

Front. Biosci. (Landmark Ed) 2021, 26(11), 1176–1190; https://doi.org/10.52586/5018
Submitted: 1 October 2021 | Revised: 29 October 2021 | Accepted: 29 October 2021 | Published: 30 November 2021
This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).
Abstract

Background: Clear cell renal cell carcinoma (ccRCC) is considered the second most common urogenital tract carcinoma, plaguing patients worldwide due to its high incidence and resistance to treatment. Thus, it is urgent to screen new biomarkers and decipher their molecular mechanisms to support early clinical diagnosis and targeted therapy of ccRCC. It is reported that epithelial membrane protein 3 (EMP3) acts as a tumor-promoting or suppressing factor in a variety of malignant tumors, but its relationship with ccRCC remains to be explored. Methods: The Cancer Genome Atlas (TCGA) and Oncomine database were utilized to screen the differentially expressed genes in ccRCC. Western blot and qPCR were used to verify the expression of our subject of interest, EMP3 in ccRCC tissues and cell lines. Next, a series of functional experiments were conducted to explore the biological functions of EMP3 in tumor cells, including cell counting kit-8, transwell, wound healing assays, Oil red O staining and triglyceride determination. Western blotting was used to explore the potential mechanism of EMP3 induced ccRCC deterioration. Finally, the TIMER2.0 database was used to explore the effect of EMP3 on tumor immune infiltration and its relationship with multiple immune checkpoints. Results: In this study, we uncovered that EMP3 was more prominently expressed in ccRCC and its expression level had a significant positive correlation with the clinical stage and histopathological grade of tumor patients. Based on the TCGA database, the Receiver operating characteristic (ROC) curves showed that EMP3 could be potentially utilized as a specific biomarker in diagnosing ccRCC patients. Meanwhile, six independent prognostic factors were determined and integrated into our nomogram, with an OS concordance index (C-index) of 0.760 (95% CI: 0.689–0.831). Furthermore, in vitro depletion of EMP3 could alleviate the proliferation, migration, invasion, and lipid storage in ccRCC cells. Mechanistically, EMP3 was shown to enhance the malignant potential of tumor cells by promoting epithelial-mesenchymal transition (EMT) and lipid accumulation. In addition, the expression of EMP3 was closely related to the infiltration of a variety of immune cells, and was positively related to PD-L1, suggesting that it may be a tight connection with tumor immune escape. Conclusions: Our results revealed that EMP3 might be a candidate biomarker and independent prognostic indicator, and related to EMT process, lipid accumulation, as well as immune infiltration in ccRCC. Targeted EMP3 therapy might be a promising and effective treatment strategy for ccRCC patients.

Keywords
Epithelial membrane protein 3
ccRCC
Biomarker
EMT
Lipid accumulation
Immune infiltration
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