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Ovarian cancer
2022-RA-1112-ESGO MFAP5 is related to ovarian cancer progression but not suitable as prognostic biomarker
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  1. Katarzyna Aleksandra Kujawa1,
  2. Ewa Zembala-Nożyńska2,
  3. Joanna Syrkis3,
  4. Alexander Jorge Cortez4,
  5. Jolanta Kupryjańczyk5 and
  6. Katarzyna Marta Lisowska3
  1. 11Center for Translational Research and Molecular Biology of Cancer, Maria Skłodowska – Curie National Research Institute of Oncology Gliwice Branch, Gliwice, Poland
  2. 2Tumor Pathology Department, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland
  3. 3Center for Translational Research and Molecular Biology of Cancer, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland
  4. 4Department of Biostatistics and Bioinformatics, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland
  5. 5Tumor Pathology Department, Maria Skłodowska-Curie National Research Institute of Oncology, Warszawa, Poland

Abstract

Introduction/Background Previously, we identified a set of genes related to differential survival of patients with high-grade serous ovarian cancer (OC).1 One of these was Microfibrillar associated protein 5 (MFAP5). MFAP5 is poorly characterized, although some data suggest that it can promote cancer cell motility and invasiveness, as well as angiogenesis in OC. Our aim was to validate MFAP5 as prognostic biomarker.

Methodology For survival analysis we used online tools: Kaplan-Meier Plotter and Microarray Gene Expression Database of OC Subtype (CSIOVDB). MFAP5 co-expressed genes were identified using cBioPortal; protein interaction networks were assessed by STRING. Immunohistochemical analysis was performed on 108 formalin-fixed paraffin-embedded OC samples and on tissue arrays (US Biomax), using anti-MFAP5 antibody (15727–1-AP, Proteintech); results were analyzed using Statistica-v.13.1 (StatSoft).

Results Kaplan-Meier Plotter and CSIOVDB analysis confirmed that MFAP5 mRNA level is significantly related to survival of OC patients. Also, patients with FIGO I&II had significantly lower MFAP5 expression than patients with advanced stage (FIGO III&IV) cancer; patients with well-differentiated (G1) tumors had lower MFAP5 expression than patients with G2&G3 tumors. Subsequently, we evaluated expression of MFAP5 protein by immunohistochemistry. Patients with highest MFAP5 level had shorter survival, however not statistically significant. MFAP5 expression was also related to desmoplastic reaction. There was no correlation neither with stage, grade, nor histological type. MFAP5 is co-expressed with multiple genes coding for extracellular-matrix proteins (cBioPortal); STRING algorithm showed strong experimental evidence for MFAP5 interactions with ECM proteins, primarily with LOX family members and FBN1. MFAP5 was shown to be connected to the Notch signaling pathway.

Conclusion MFAP5 seem to be involved in the important cellular processes and signaling pathways engaged in cancer progression and its mRNA level is related to worse prognosis. However, MFAP5 is not suitable as prognostic marker for simple evaluation with IHC.

Reference

  1. Lisowska KM, et al. (2016). doi:10.1007/s00432-016-2147-y.

https://doi.org/10.1136/ijgc-2022-ESGO.641

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