DGAT1 Expression Promotes Ovarian Cancer Progression and Is Associated with Poor Prognosis

J Immunol Res. 2021 May 14:2021:6636791. doi: 10.1155/2021/6636791. eCollection 2021.

Abstract

Background: Ovarian cancer is the most fatal gynecological malignancy. Owing to its insidious onset, rapid development, and poor prognosis, ovarian cancer is the fifth most common cause of death in women. Although immunotherapy-related drugs, such as Olaparib, can alleviate ovarian cancer progression, there are no remarkable breakthroughs for its effective treatment. It is considered that the transformation of normal cells to cancerous ones involves "recoding" of certain metabolic pathways. Diacylglycerol O-acyltransferase 1 (DGAT1) can synthesize triglycerides by transferring acyl-CoA to diacylglycerol, which plays a key role in lipid synthesis. However, the role of DGAT1 in ovarian cancer is not yet elucidated.

Materials and methods: We analyzed the correlation between DGAT1 and ovarian cancer staging, grading, vascular invasion, and prognosis by collating the information of ovarian cancer specimens from The Cancer Genome Atlas (TCGA) database. Furthermore, the effects of DGAT1 expression on proliferation, migration, invasion, and tumor growth were studied using ovarian cancer cell lines. GSEA was used to analyze the KEGG pathways and biological function enriched because of DGAT1 expression in ovarian cancer.

Results: The expression of DGAT1 was elevated in advanced (p = 0.0432), poorly differentiated (p = 0.0148), and vascular invaded (p = 0.0002) ovarian cancer specimens. Prognosis among patients with high expression of DGAT1 was poor. After DGAT1 expression was interfered, proliferation, migration, invasion, colony forming, and tumor growth of ovarian cancer cells were inhibited. In addition, GSEA showed that DGAT1 may be involved in the immune process.

Conclusion: DGAT1 expression is associated with the clinical phenotype of ovarian cancer. We suggest that DGAT1 has potential implications in the treatment of ovarian cancer.

MeSH terms

  • Animals
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Line, Tumor
  • Diacylglycerol O-Acyltransferase / analysis
  • Diacylglycerol O-Acyltransferase / genetics
  • Diacylglycerol O-Acyltransferase / metabolism*
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Kaplan-Meier Estimate
  • Mice
  • Neoplasm Grading
  • Neoplasm Staging
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Ovary / enzymology
  • Ovary / pathology*
  • Prognosis
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • DGAT1 protein, human
  • Diacylglycerol O-Acyltransferase