Abstract
Simple Summary: The study investigated the prostate cancer microenvironment and the correlation between peritumoral collagen and aggressivity of cancer. We used novel and advanced imaging including next-generation sequencing to characterise the expression of collagen in the extracellular matrix. Type and contents of collagen varied according to the Gleason grade in prostate cancer in men with localised prostate cancer undergoing radical surgery. The collagen contents orientation seen on second harmonic generation imaging varied with the grade of cancer and can predict clinically significant prostate cancer. Increased expression of Col1A1 is present in cancer tissues and associated with increased tissue modulus as measured by ultrasound shear wave elastography in prostate cancer. The study adds knowledge to our understanding of prostate cancer and defines the microenvironment of clinically significant prostate cancer, a disease more likely to impact survival and outcome of men who suffer from it.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.