Microfibril Associated Protein 5 (MFAP5) Is Related to Survival of Ovarian Cancer Patients but Not Useful as a Prognostic Biomarker

Int J Mol Sci. 2022 Dec 15;23(24):15994. doi: 10.3390/ijms232415994.

Abstract

Ovarian cancer (OC) is usually diagnosed late due to its nonspecific symptoms and lack of reliable tools for early diagnostics and screening. OC studies concentrate on the search for new biomarkers and therapeutic targets. This study aimed to validate the MFAP5 gene, and its encoded protein, as a potential prognostic biomarker. In our previous study, we found that patients with high-grade serous OC who had higher MFAP5 mRNA levels had shorter survival, as compared with those with lower levels. Here, we used the Kaplan-Meier Plotter and CSIOVDB online tools to analyze possible associations of MFAP5 expression with survival and other clinico-pathological features. In these analyses, higher MFAP5 mRNA expression was observed in the more advanced FIGO stages and high-grade tumors, and was significantly associated with shorter overall and progression-free survival. Next, we analyzed the expression of the MFAP5 protein by immunohistochemistry (IHC) in 108 OC samples and tissue arrays. Stronger MFAP5 expression was associated with stronger desmoplastic reaction and serous vs. non-serous histology. We found no significant correlation between IHC results and survival, although there was a trend toward shorter survival in patients with the highest IHC scores. We searched for co-expressed genes/proteins using cBioPortal and analyzed potential MFAP5 interaction networks with the STRING tool. MFAP5 was shown to interact with many extracellular matrix proteins, and was connected to the Notch signaling pathway. Therefore, although not suitable as a prognostic biomarker for evaluation with a simple diagnostic tool like IHC, MFAP5 is worth further studies as a possible therapeutic target.

Keywords: CSIOVDB; Kaplan-Meier plotter; MAGP2; MFAP5; cBioPortal; immunohistochemistry; microfibril-associated glycoprotein 2; microfibril-associated protein 5; ovarian cancer; prognostic markers; string.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Contractile Proteins* / genetics
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Microfibrils / metabolism
  • Ovarian Neoplasms* / diagnosis
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / metabolism
  • Prognosis
  • RNA, Messenger / metabolism

Substances

  • Contractile Proteins
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Biomarkers, Tumor