A Blood-Based Immune Gene Signature with Prognostic Significance in Localized Prostate Cancer

Simple Summary The discovery of prognostic biomarkers constitutes an important issue because it allows the tailoring of therapeutic treatments, thus avoiding over-treatment and side effects. In this context, reliable prognostic biomarkers advance the field of precision oncology. Such biomarkers are usually discovered in the tumor tissue, which is not an easy task given the inaccessibility of malignant tissue in many types of cancer. In this work, we could identify a prognostic signature consisting of eight genes for prostate cancer patients. This biosignature was identified in peripheral blood samples, which are easy to access and, importantly, have a significant prognostic value for various types of cancer. Prostate cancer (PCa) is one of the most common male cancers worldwide and one of the deadliest if unsuccessfully treated. & tau;he need for reliable, easily accessible immune-related molecular biomarkers that could be combined with clinically defined criteria, including PSA and Gleason score, to accurately predict PCa patients' clinical outcomes is emerging. Herein, we describe for the first time a blood-identified immune-related gene signature comprising eight upregulated multi-functional genes associated with poor prognosis. Next-generation sequencing (NGS) analysis of PCa patients' peripheral blood samples revealed a more than three-fold upregulation of each of the eight genes as compared to samples originating from healthy donors. The construction of gene and protein interaction networks revealed different extents of the functional implications of these genes in the regulation of cell proliferation and immune responses. Analysis of the available data from The Cancer Genome Atlas (TCGA) regarding gene expression and survival of prostate adenocarcinoma (PRAD) and pan-cancer (PANCAN) patients revealed that intra-tumoral upregulation of this eight-gene signature (8-GS) was associated with poor 5-year progression-free intervals in PCa patients, even in those with high Gleason scores, and also with an unfavorable prognosis for cancer patients irrespective of the cancer type and even in the early stages. These observations suggest that further investigation of the 8-GS prospectively in randomized clinical trials, in which clinical benefit in terms of evaluating time to disease progression can be assessed, is warranted.

Automated summary

The discovery of prognostic biomarkers is important for personalized treatment and precision oncology. In this study, a prognostic signature consisting of eight genes was identified in peripheral blood samples of prostate cancer patients, which can be easily accessed and have significant prognostic value for various types of cancer.