# Identification of Proteins Associated with Ovarian Cancer Chemotherapy Resistance Using MALDI-MSI

## TL;DR

This study identifies proteins linked to chemotherapy resistance in ovarian cancer using advanced imaging techniques, offering potential new targets for treatment.

## Contribution

The study introduces novel proteins associated with chemotherapy resistance in high-grade serous ovarian cancer.

## Key findings

- Proteins like COL12A1 and PLEC are upregulated in chemotherapy-resistant ovarian cancer tissues.
- Higher levels of COL12A1 and PLEC correlate with reduced progression-free survival in patients.
- These proteins are potential biomarkers and therapeutic targets for resistant ovarian cancer.

## Abstract

Ovarian cancer is the most lethal gynecological cancer. Up to 75% of cases are high-grade serous ovarian cancer (HGSOC) that have high chemosensitivity to first-line platinum-based therapies. However, 75% of patients will become chemoresistant following relapse. The underlying mechanism for developing resistance to chemotherapy in HGSOC is poorly understood. In this study, we employed Matrix-Assisted Laser Desorption/Ionization–Mass Spectrometry Imaging (MALDI-MSI) on matching formalin-fixed paraffin-embedded (FFPE) HGSOC tissues at the time of diagnosis and following relapse with chemotherapy-resistant disease (n = 4). We identified m/z values that were differentially abundant in the matching diagnosis and relapse HGSOC tissues. These were matched to proteins using nano-liquid chromatography tandem mass spectrometry (LC-MS/MS). We identified upregulated proteins in the HGSOC relapse tissues, including COL12A1, FUBP1, PLEC, SLC4A1, and TKT. These proteins were validated by immunohistochemistry (IHC) and gene expression using online databases. IHC showed COL12A1, FUBP1, PLEC, SLC4A1, and TKT protein abundance were significantly elevated in HGSOC relapse tissues compared to matching tissues at diagnosis. COL12A1, FUBP1, PLEC, and TKT mRNA expression levels were significantly increased in HGSOC compared to normal ovary and associated with poor prognosis in HGSOC. We confirmed that higher protein abundance of both COL12A1 and PLEC correlated with reduced progression-free survival in HGSOC patients. Furthermore, both COL12A1 and PLEC mRNA and protein levels were significantly associated with chemotherapy resistance. In summary, using MALDI-MSI, we have identified proteins, including COL12A1 and PLEC, associated with chemotherapy resistance to be further evaluated as HGSOC biomarkers and/or therapeutic targets.