An Integrative Multi-Omics Data-Driven Identification of Key Molecular and Cellular Alterations in Prostate Cancer: A Translational Genomics Approach

Abstract

Prostate cancer stands as a prominent malignancy of the prostate gland, a

leading cause of male mortality globally. This cancerous growth disrupts the pro- duction of prostatic fluid, integral for sperm transportation and safeguarding. Pro- gression of this cancer is steered by flawed cell signaling, immune response and

gene expression, ultimately enabling evasion, expansion, and metastasis. Conven- tional treatments often spur drug resistance and a more aggressive cancer phenotype.

This study utilized bulk and single-cell RNA-sequencing techniques to delve into the fundamental molecular and cellular changes underpinning prostate cancer with

focus towards immune response from both tumor and normal prostate glands. Out- comes spotlighted 1,634 differentially expressed genes, notably introducing novel

noncoding (SCARNA3, SNORA74D, SNORD70) and coding (MSTRG.11932.6,

MSTRG.28256.4, MSTRG.25472.3) alternatively spliced transcripts involved in im- mune responses and crosstalk. Furthermore, detailed scrutiny at the single-cell level

unveiled dampened anti-tumor pathways, such as TCR and MHC-II, spanning various immune cell categories, thus signifying a compromised tumor microenvironment from an immunological standpoint. Conversely, pathways propelling tumor advancement,

including interleukins, maintained consistent elevation, fostering prolonged inflam- mation that propels tumor growth while circumventing immune vigilance. Cell-cell

communication analysis revealed the role of IL-2 and IL-4 pathways in nurturing

immunosuppression within the tumor microenvironment through T-cell anergy, fa- cilitated through CD4+ NKT-like, CD8+ NKT-like and memory CD4+ cells. This

comprehensive approach further pinpointed the disruption of key signaling molecules

(IL2RG, IL2RB, IL7R), involved in IL-2 and IL-4 pathways inhibited essential im- mune response pathways, such as TCR and MHC-II antigen presentation, crucial for

anti-cancer activities. This study identifies novel (IL2RB, IL2RG) cancer immunother- apy targets for targeted immunotherapy against prostate cancer.