MRPL15 is a novel prognostic biomarker and therapeutic target for epithelial ovarian cancer

Cancer Med. 2021 Jun;10(11):3655-3673. doi: 10.1002/cam4.3907. Epub 2021 May 2.

Abstract

Purpose: To analyze the role of six human epididymis protein 4 (HE4)-related mitochondrial ribosomal proteins (MRPs) in ovarian cancer and selected MRPL15, which is most closely related to the tumorigenesis and prognosis of ovarian cancer, for further analyses.

Methods: Using STRING database and MCODE plugin in Cytoscape, six MRPs were identified among genes that are upregulated in response to HE4 overexpression in epithelial ovarian cancer cells. The Cancer Genome Atlas (TCGA) ovarian cancer, GTEX, Oncomine, and TISIDB were used to analyze the expression of the six MRPs. The prognostic impact and genetic variation of these six MRPs in ovarian cancer were evaluated using Kaplan-Meier Plotter and cBioPortal, respectively. MRPL15 was selected for immunohistochemistry and GEO verification. TCGA ovarian cancer data, gene set enrichment analysis, and Enrichr were used to explore the mechanism of MRPL15 in ovarian cancer. Finally, the relationship between MRPL15 expression and immune subtype, tumor-infiltrating lymphocytes, and immune regulatory factors was analyzed using TCGA ovarian cancer data and TISIDB.

Results: Six MRPs (MRPL10, MRPL15, MRPL36, MRPL39, MRPS16, and MRPS31) related to HE4 in ovarian cancer were selected. MRPL15 was highly expressed and amplified in ovarian cancer and was related to the poor prognosis of patients. Mechanism analysis indicated that MRPL15 plays a role in ovarian cancer through pathways such as the cell cycle, DNA repair, and mTOR 1 signaling. High expression of MRPL15 in ovarian cancer may be associated with its amplification and hypomethylation. Additionally, MRPL15 showed the lowest expression in C3 ovarian cancer and was correlated with proliferation of CD8+ T cells and dendritic cells as well as TGFβR1 and IDO1 expression.

Conclusion: MRPL15 may be a prognostic indicator and therapeutic target for ovarian cancer. Because of its close correlation with HE4, this study provides insights into the mechanism of HE4 in ovarian cancer.

Keywords: MRPL15; bioinformatics; mitochondrial ribosomal protein; ovarian cancer; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • CD8-Positive T-Lymphocytes / cytology
  • Carcinoma, Ovarian Epithelial / chemistry
  • Carcinoma, Ovarian Epithelial / genetics
  • Carcinoma, Ovarian Epithelial / metabolism*
  • Carcinoma, Ovarian Epithelial / pathology
  • Cell Proliferation / genetics
  • Databases, Genetic
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Mitochondrial Proteins / analysis
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Ovarian Neoplasms / chemistry
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Ovary / chemistry
  • Ovary / metabolism
  • Prognosis
  • RNA, Messenger / analysis
  • RNA-Binding Proteins / analysis
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Ribosomal Proteins / analysis
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism*
  • Up-Regulation
  • WAP Four-Disulfide Core Domain Protein 2 / analysis
  • WAP Four-Disulfide Core Domain Protein 2 / genetics
  • WAP Four-Disulfide Core Domain Protein 2 / metabolism*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • MRPL15 protein, human
  • Mitochondrial Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Ribosomal Proteins
  • WAP Four-Disulfide Core Domain Protein 2
  • WFDC2 protein, human