Characterisation of Collagen Re-Modelling in Localised Prostate Cancer Using Second-Generation Harmonic Imaging and Transrectal Ultrasound Shear Wave Elastography

Prostate cancer has a poor prognosis and high mortality rate due to metastases. Extracellular matrix (ECM) re-modelling and stroma composition have been linked to cancer progression, including key components of cell migration, tumour metastasis, and tissue modulus. Moreover, collagens are one of the most significant components of the extracellular matrix and have been ascribed to many aspects of neoplastic transformation. This study characterises collagen re-modelling around localised prostate cancer using the second harmonic generation of collagen (SHG), genotyping and ultrasound shear wave elastography (USWE) measured modulus in men with clinically localised prostate cancer. Tempo-sequence assay for gene expression of COL1A1 and COL3A1 was used to confirm the expression of collagen. Second-harmonic generation imaging and genotyping of ECM around prostate cancer showed changes in content, orientation, and type of collagen according to Gleason grades (cancer aggressivity), and this correlated with the tissue modulus measured by USWE in kilopascals. Furthermore, there were clear differences between collagen orientation and type around normal and cancer tissues.

Matrisome Deregulation in Ovarian Cancer Metastasis

Background and Hypothesis: Over 75% of ovarian cancer (OC) patients present with metastasis upon initial diagnosis. Since most are treated for metastatic disease, it is crucial that developing therapies target metastasis. Our analysis of OC transcriptomic changes revealed key changes in the matrisome. Matrisome genes are associated with tissue modulus and disease progression, yet comprehensive understanding of many of their contributions to OC is lacking. We hypothesize that matrisomal OC genes will have clear impacts on clinical outcomes. Project Methods: Differentially expressed genes (DEG) in 11 paired OC primary tumors and metastases were identified using RNA-seq analysis. The DEG were compared with data from high-grade serous ovarian cancer (HGSOC) cells seeded on an organotypic 3D culture model of omentum. The overlapping genes are deregulated during early metastasis and remain relevant in advanced metastasis in OC patients. Kaplan-Meier Plots were generated to identify gene relationships with progression-free survival (PFS) and overall survival (OS). Results: 845 genes between metastases and primary tumors and 1,182 genes between early and advanced metastatic colonization were differentially expressed; 144 genes were shared. These 144 genes were compared with matrisome proteins differentially expressed between malignant and non-malignant HGSOC cell populations. 28 genes correlated with tissue modulus, 19 with disease score, and 17 with both. Of the 30 matrisome genes correlating with either, 21 decreased PFS and 24 decreased OS. Conclusion and Potential Impact: We have identified a matrisome signature sustained throughout metastatic tumor development. Many of these genes’ mechanisms contributing to OC metastasis and therapeutic relevance have yet to be determined. In addition to influencing cell-cell communications, mechanotransduction, and metastasis progression, the altered matrisome can affect drug delivery to tumors. Further studies may guide understanding of pathways in matrisome alteration during cancer progression and reveal future targets for chemotherapy or combination immunotherapies.