Search bioRxiv⌕ Search

bioRxiv · 10.1101/2023.07.27.550781

Artificial Intelligence Helps to Predict Recurrence and Mortality for Prostate Cancer using Histology Images

Abstract

Besides grading, deep learning could improve expert consensus to predict prostate cancer (PCa) recurrence. We developed a novel PCa recurrence prediction system based on artificial intelligence (AI). We validated it using multi-institutional and international datasets comprising 2,647 PCa patients with at least a 10-year follow-up. Survival analyses were performed and goodness-of-fit of multivariate models was evaluated using partial likelihood ratio tests, Akaikes test, or Bayesian information criteria to determine the superiority of our system over existing grading systems. Comprehensive survival analyses demonstrated the effectiveness of our AI- system in categorizing PCa into four distinct risk groups. The system was independent and superior to the existing five grade groups for malignancies. A high consensus level was observed among five blinded genitourinary pathology experts in ranking images according to our prediction system. Therefore, AI may help develop an accurate and clinically interpretable PCa recurrence prediction system, facilitating informed decision-making for PCa patients.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Eminaga, O., Saad, F., Tian, Z., Wolffgang, U., Karakiewicz, P. I., Ouellet, V., Azzi, F., Spieker, T., Helmke, B. M., Graefen, M., Jiang, X., Xing, L., Witt, J. H., Trudel, D., Leyh-Bannurah, S.-R.. 2023-07-31. Artificial Intelligence Helps to Predict Recurrence and Mortality for Prostate Cancer using Histology Images. https://doi.org/10.1101/2023.07.27.550781

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

NAE1-Dependent Protein Neddylation Preserves Endothelial Identity and Vascular Integrity

Background: Endothelial dysfunction is a central driver of cardiovascular and inflammatory diseases, yet the post-translational mechanisms that preserve endothelial homeostasis remain incompletely understood. Protein neddylation, the covalent conjugation of a ubiquitin-like modifier, regulates diverse cellular processes, yet its physiological role in the vascular endothelium remains unknown. This study investigated whether protein neddylation is required to preserve endothelial identity and vascular homeostasis. Methods: We generated tamoxifen-inducible endothelial-specific Nae1 knockout mice to inhibit neddylation and combined bulk RNA sequencing, single-cell and single-nucleus transcriptomics, quantitative proteomics, biochemical analyses, and gain- and loss-of-function approaches to define the role of endothelial neddylation in vascular homeostasis and inflammatory injury. Results: Endothelial-specific Nae1 deletion caused rapid mortality associated with vascular leakage, platelet accumulation, inflammation, and multi-organ injury. Multi-omics analyses demonstrated profound loss of endothelial identity, characterized by suppression of core endothelial programs and activation of inflammatory, procoagulant, and pyroptotic pathways. Single-cell analyses revealed progressive endothelial dysfunction culminating in depletion of the endothelial population and remodeling of the vascular niche. Mechanistically, endothelial neddylation deficiency activated gasdermin D (GSDMD)- and gasdermin E (GSDME)-dependent pyroptosis, whereas dual inhibition of GSDMD and GSDME markedly attenuated inflammatory transcriptomic remodeling, vascular injury, hepatocyte death, immune cell infiltration, and platelet accumulation. Translational analyses demonstrated reduced endothelial neddylation in experimental endotoxemia and decreased expression of neddylation pathway components in human atherosclerosis and COVID-19 datasets. Conversely, restoration of endothelial neddylation partially reversed inflammatory endothelial transcriptomic reprogramming in vivo. Conclusions: NAE1-dependent protein neddylation is an essential regulator of endothelial identity and vascular integrity. Loss of endothelial neddylation promotes gasdermin-dependent pyroptosis and thrombo-inflammatory vascular injury, whereas restoration of the neddylation pathway mitigates inflammatory endothelial dysfunction. These findings identify endothelial neddylation as a fundamental mechanism maintaining vascular homeostasis and a potential therapeutic target for cardiovascular and inflammatory diseases.

pathology↗

Integrin alpha1 beta1 promotes interstitial fibrosis in a mouse model of polycystic kidney disease

Fibrosis is the cause of end-stage kidney failure in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD). The molecular and cellular mechanisms involved in fibrosis are complex and anti-fibrotic therapies have so far failed to make an impact on patient welfare. Using unbiased proteomics analysis on the Pkd1nl/nl mouse, we found that expression of the integrin 1 subunit is increased in this model of ADPKD. In human ADPKD tissue and two single cell RNA kidney disease datasets, ITGA1 was also upregulated. To investigate the functional role of this integrin subunit in ADPKD, we generated a Pkd1nl/nlItga1-/- mouse. We observed a significant reduction in kidney volume and kidney dysfunction in mice lacking the integrin 1 subunit. Kidneys from Pkd1nl/nlItga1-/- mice had smaller cysts and reduced interstitial expansion and tubular atrophy. Picrosirius red staining identified a restriction in collagen staining in the interstitium and the myofibroblast marker smooth muscle actin was also downregulated. Myofibroblast cell proliferation was reduced in Pkd1nl/nlItga1-/- mice and primary fibroblast cultures demonstrated an abrogated fibrogenic phenotype in integrin 1-depleted fibroblasts. These results highlight a previously unrecognised role for the integrin 1 subunit in kidney fibrosis.

pathology↗

Evaluating the Biocontrol Potential of Pythium oligandrum and Serratia proteamaculans in Controlling Phytophthora plurivora in European beech (Fagus sylvatica)

In recent years, the plant pathogen Phytophthora plurivora has caused severe damage to beech forests in many European countries, including Sweden. In many affected areas, few protective measures are in place due to fears about potential negative impacts on the ecosystem or public health. The research presented in this article assesses the biocontrol potential of the oomycete Pythium oligandrum and the bacterium Serratia proteamaculans against P. plurivora, with experiments performed under both in vitro and greenhouse conditions, which could represent a step forward in developing a safe treatment for European beech forests. The in vitro results revealed that P. oligandrum and S. proteamaculans significantly inhibited pathogen growth and stimulated a shift in the hyphal growth pattern towards shorter, branched hyphae with many hyphal swellings and thickened cell walls. The experiments conducted in greenhouses showed that treating three-month-old beech seedlings with P. oligandrum and S. proteamaculans counteracts the P. plurivora pathogen and reduces disease symptoms on the aerial and underground parts of the plant. GC-MS analysis detected the volatile organic compounds alpha-pinene, 2,5-dimethyl-pyrazine, and 3-methyl-1-butanol from S. proteamaculans; these compounds have the potential to inhibit pathogen growth. The disease suppression demonstrated by these biocontrol agents could thus be related to the synergistic effect of competition for nutrients with the secretion of hydrolytic enzymes and VOCs; moreover, induced systemic resistance may be triggered under greenhouse conditions. In conclusion, using P. oligandrum and S. proteamaculans could represent an environmentally friendly strategy for effectively controlling the disease caused by P. plurivora in beech.

pathology↗