Pawel Knapp

Rare presentation of mucinous ovarian cancer with aggressive features and unusual metastatic pattern

Repurposing of PI3K inhibitors for high-grade serous ovarian cancer: A novel competing endogenous network analysis-based approach

The average survival time for High-Grade Serous Ovarian Cancer (HGSOC) is around 3.4 years post-diagnosis. The treatment options are limited, especially for relapsed patients, resistant to standard treatment. Therefore, novel drug candidates are needed. We propose a novel approach for predicting potential drug candidates by focusing on agents capable of reversing the effects of perturbed RNA network. The competing endogenous RNA (ceRNAs) network was constructed on differential expression (DE) of long non-coding RNAs (lncRNAs), protein-coding RNAs (mRNAs) and microRNAs (miRNAs) from the primary HGSOC tumour tissues. It allowed for identification of key perturbed axes of RNA regulation. The publicly available resources for drug repurposing were used to select candidates for in-vitro validation. The phosphoinositide 3-kinase (PI3K) pathway, known to be involved in developing drug resistance in ovarian cancer, was identified as highly dependent from the coding and non-coding RNA interactions. PI3K pathway inhibitors, PI-103 and ZSTK474, were identified as drug candidates and their efficacy against HGSOC was confirmed in vitro. E2F1 and SNAI2 are essential transcription factors (TFs) known for regulating critical cancer pathways such as cell cycle repair or epithelial-mesenchymal transition (EMT). In our study, these TFs were identified as hub regulators within the ceRNA network. Investigation of fine-tune regulation of RNA by non-coding RNAs and TFs uncovered a significant role of ceRNA network in cancer development, highlighting its integration with master regulatory pathways that drive tumor progression and sustainability. The drug repurposing workflow based on ceRNA-limited differentially expressed mRNAs allowed for effective prioritization of compounds with potential to be applied as treatment.

Diagnostic Utility of Selected Matrix Metalloproteinases (MMP-2, MMP-3, MMP-11, MMP-26), HE4, CA125 and ROMA Algorithm in Diagnosis of Ovarian Cancer

Ovarian cancer (OC) has an unfavorable prognosis. Due to the lack of effective screening tests, new diagnostic methods are being sought to detect OC earlier. The aim of this study was to evaluate the concentration and diagnostic utility of selected matrix metalloproteinases (MMPs) as OC markers in comparison with HE4, CA125 and the ROMA algorithm. The study group consisted of 120 patients with OC; the comparison group consisted of 70 patients with benign lesions and 50 healthy women. MMPs were determined via the ELISA method, HE4 and CA125 by CMIA. Patients with OC had elevated levels of MMP-3 and MMP-11, similar to HE4, CA125 and ROMA values. The highest SE, SP, NPV and PPV values were found for MMP-26, CA125 and ROMA in OC patients. Performing combined analyses of ROMA with selected MMPs increased the values of diagnostic parameters. The topmost diagnostic power of the test was obtained for MMP-26, CA125, HE4 and ROMA and performing combined analyses of MMPs and ROMA enhanced the diagnostic power of the test. The obtained results indicate that the tested MMPs do not show potential as stand-alone OC biomarkers, but can be considered as additional tests to raise the diagnostic utility of the ROMA algorithm.