Identification of immune-based prostate cancer subtypes using mRNA expression.

Jukun Song,Jianguo Zhu,Dongbo Yuan,Jiaming Su,Weihong Chen,Yong Ban,Yiwen Yuan,Wei Wang

doi:10.1042/bsr20201533

Abstract

Immune infiltration in Prostate Cancer (PCa) was reported to be strongly associated with clinical outcomes. However, previous research could not elucidate the diversity of different immune cell types that contribute to the functioning of the immune response system. In the present study, the CIBERSORT method was employed to evaluate the relative proportions of immune cell profiling in PCa samples, adjacent tumor samples and normal samples. Three types of molecular classification were identified in tumor samples using the ‘CancerSubtypes’ package of the R software. Each subtype had specific molecular and clinical characteristics. In addition, functional enrichment was analyzed in each subtype. The submap and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms were also used to predict clinical response to the immune checkpoint blockade. Moreover, the Genomics of Drug Sensitivity in Cancer (GDSC) database was employed to screen for potential chemotherapeutic targets for the treatment of PCa. The results showed that Cluster I was associated with advanced PCa and was more likely to respond to immunotherapy. The findings demonstrated that differences in immune responses may be important drivers of PCa progression and response to treatment. Therefore, this comprehensive assessment of the 22 immune cell types in the PCa Tumor Environment (TEM) provides insights on the mechanisms of tumor response to immunotherapy and may help clinicians explore the development of new drugs.

Highlights

Prostate Cancer (PCa) is the most common malignancy in Europe and the United States
Healthy human prostate tissues were available from the GTEx database, while tumor and adjacent tumor samples samples were obtained from The Cancer Genome Atlas (TCGA)
Twenty-one types of Tumor Infiltrating Leukocyte (TIL) were detected in patients, while naive CD4+ T cells were absent from most of the samples, consistent with a previous report [25]

Summary

Introduction

Prostate Cancer (PCa) is the most common malignancy in Europe and the United States. The disease has resulted in the second highest number of mortalities, after breast cancer, in American male patients [1]. The American Cancer Society reported 174650 new PCa cases in 2019 alone ranking first and accounting for 20% of all new male cancer cases. 31620 deaths were reported from PCa in 2019, accounting for 10% of all cancer-related deaths [2]. There are obvious ethnic differences in the incidence of PCa. For instance, the incidence and mortality rate of PCa in China is lower than that of Western countries including Europe and the United States. Given the recent changes in society and people’s lifestyles, PCa has become common among males with increased incidence rates every year [4]. The significant differences in incidence and morbidity may be due to genomic instability and changes associated with various PCa risk factors

Objectives

Methods

Results

Discussion

Conclusion