Clinicopathological and prognostic significance of caveolin-1 and ATG4C expression in the epithelial ovarian cancer

PLoS One. 2020 May 13;15(5):e0232235. doi: 10.1371/journal.pone.0232235. eCollection 2020.


Objective: Altered expression of caveolin-1 (CAV1) and autophagy marker ATG4C is observed in various types of human cancers. However, the clinical significance of CAV1 and ATG4C expression in epithelial ovarian cancer (EOC) remains largely unknown. The present study aims to explore the clinicopathological value and prognostic significance of CAV1 and ATG4C expression in EOC.

Methods: The expression pattern and prognostic value of CAV1 and ATG4C mRNA in EOC were analyzed using data from the Cancer Genome Atlas (TCGA) database (N = 373). In addition, immunohistochemistry analysis was performed to detect and assay the expression of CAV1 and ATG4C proteins in tissue microarray of EOC.

Results: Based on TCGA data, Kaplan-Meier analysis indicated that patients with low CAV1 mRNA (p = 0.021) and high ATG4C mRNA (p = 0.018) expression had a significantly shorter overall survival (OS). Cox regression analysis demonstrated that the expression levels of CAV1 (p = 0.023) and ATG4C mRNA (p = 0.040) were independent prognostic factors for OS in EOC. In addition, the Concordance Index of the nomogram for OS prediction was 0.660. Immunohistochemical analysis showed the expression levels of stromal CAV1 and cancerous ATG4C proteins, and high expression of both CAV1 and ATG4C protein in the stroma were found to significantly correlate with the histologic subtypes of EOC, especially with serous subtype.

Conclusions: Decreased expression of CAV1 mRNA and increased expression of ATG4C mRNA in EOC can predict poor overall survival. The expression levels of CAV1 protein in stromal cells and ATG4C protein in cancer cells are significantly associated with histologic subtypes of EOC. These findings suggest that CAV1 and ATG4C serve as useful prognostic biomarkers and candidate therapeutic targets in EOC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Autophagy-Related Proteins / metabolism*
  • Carcinoma, Ovarian Epithelial / diagnosis*
  • Carcinoma, Ovarian Epithelial / metabolism
  • Carcinoma, Ovarian Epithelial / pathology*
  • Caveolin 1 / metabolism*
  • Cysteine Endopeptidases / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Prognosis
  • Survival Analysis
  • Young Adult


  • Autophagy-Related Proteins
  • Caveolin 1
  • ATG4A protein, human
  • Cysteine Endopeptidases

Grant support

This work was supported by the Joint Grant of Health Commission of Hubei Province (WJ2018H0151) for Dr.Hu and the Innovation Project of Wuhan University Medical School (No. MS2016001) for DR. Zeng. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.