Discovery of Prognostic Markers for Early-Stage High-Grade Serous Ovarian Cancer by Maldi-Imaging.
Hagen KulbeOliver KleinZhiyang WuEliane T TaubeWanja KassuhnDavid HorstSilvia Darb-EsfahaniPaul JankSalem AbobakerFrauke RingelAndreas du BoisFlorian HeitzJalid SehouliElena I BraicuPublished in: Cancers (2020)
With regard to relapse and survival, early-stage high-grade serous ovarian (HGSOC) patients comprise a heterogeneous group and there is no clear consensus on first-line treatment. Currently, no prognostic markers are available for risk assessment by standard targeted immunohistochemistry and novel approaches are urgently required. Here, we applied MALDI-imaging mass spectrometry (MALDI-IMS), a new method to identify distinct mass profiles including protein signatures on paraffin-embedded tissue sections. In search of prognostic biomarker candidates, we compared proteomic profiles of primary tumor sections from early-stage HGSOC patients with either recurrent (RD) or non-recurrent disease (N = 4; each group) as a proof of concept study. In total, MALDI-IMS analysis resulted in 7537 spectra from the malignant tumor areas. Using receiver operating characteristic (ROC) analysis, 151 peptides were able to discriminate between patients with RD and non-RD (AUC > 0.6 or < 0.4; p < 0.01), and 13 of them could be annotated to proteins. Strongest expression levels of specific peptides linked to Keratin type1 and Collagen alpha-2(I) were observed and associated with poor prognosis (AUC > 0.7). These results confirm that in using IMS, we could identify new candidates to predict clinical outcome and treatment extent for patients with early-stage HGSOC.
Keyphrases
- early stage
- high grade
- mass spectrometry
- poor prognosis
- low grade
- high resolution
- liquid chromatography
- risk assessment
- long non coding rna
- sentinel lymph node
- end stage renal disease
- capillary electrophoresis
- gas chromatography
- newly diagnosed
- chronic kidney disease
- ejection fraction
- high performance liquid chromatography
- prognostic factors
- gene expression
- peritoneal dialysis
- squamous cell carcinoma
- small molecule
- lymph node
- genome wide
- human health
- binding protein
- cancer therapy
- density functional theory