Plasma Cell Subtypes Analyzed Using Artificial Intelligence Algorithm for Predicting Biochemical Recurrence, Immune Escape Potential, and Immunotherapy Response of Prostate Cancer

Background: Plasma cells as an important component of immune microenvironment plays a crucial role in immune escape and are closely related to immune therapy response. However, its role for prostate cancer is rarely understood. In this study, we intend to investigate the value of a new plasma cell molecular subtype for predicting the biochemical recurrence, immune escape and immunotherapy response in prostate cancer.

Methods: Gene expression and clinicopathological data were collected from 481 prostate cancer patients in the Cancer Genome Atlas. Then, the immune characteristics of the patients were analyzed based on plasma cell infiltration fractions. The unsupervised clustering based machine learning algorithm was used to identify the molecular subtypes of the plasma cell. And the characteristic genes of plasma cell subtypes were screened out by three types of machine learning models to establish an artificial neural network for predicting plasma cell subtypes. Finally, the prediction artificial neural network of plasma cell infiltration subtypes was validated in an independent cohort of 449 prostate cancer patients from the Gene Expression Omnibus.

Results: The plasma cell fraction in prostate cancer was significantly decreased in tumors with high T stage, high Gleason score and lymph node metastasis. In addition, low plasma cell fraction patients had a higher risk of biochemical recurrence. Based on the differential genes of plasma cells, plasma cell infiltration status of PCa patients were divided into two independent molecular subtypes(subtype 1 and subtype 2). Subtype 1 tends to be immunosuppressive plasma cells infiltrating to the PCa region, with a higher likelihood of biochemical recurrence, more active immune microenvironment, and stronger immune escape potential, leading to a poor response to immunotherapy. Subsequently, 10 characteristic genes of plasma cell subtype were screened out by three machine learning algorithms. Finally, an artificial neural network was constructed by those 10 genes to predict the plasma cell subtype of new patients. This artificial neural network was validated in an independent validation set, and the similar results were gained.

Conclusions: Plasma cell infiltration subtypes could provide a potent prognostic predictor for prostate cancer and be an option for potential responders to prostate cancer immunotherapy.