Advances in Brain Metastases Diagnosis: Non-coding RNAs As Potential Biomarkers

Abstract

Brain metastasis is considered the most common brain tumor. They arise from different primary cancers. The most common primary tumors giving brain metastases include breast, colorectal, lung, melanoma, and renal cancer. Depending only on history, physical examination, and conventional imaging modalities makes brain tumors diagnosis difficult. Rapid and non-invasive promising modalities could diagnose and differentiate between different brain metastases without exposing the patients to unnecessary brain surgeries for biopsies. One of these promising modalities is non-coding RNAs (ncRNAs). NcRNAs can determine brain metastases' prognosis, chemoresistance, and radioresistance. It also helps us to understand the pathophysiology of brain metastases development. Additionally, ncRNAs may work as potential therapeutic targets for brain metastases treatment and prevention. Herein, we present deregulated ncRNAs in different brain metastases, including microRNAs and long non-coding RNAs (lncRNAs), such as gastric adenocarcinoma, colorectal, breast, melanoma, lung, and prostate cancer. Additionally, we focus on serum and cerebrospinal fluid (CSF) expression of these ncRNAs in patients with brain metastases compared to patients with primary tumors. Moreover, we discuss the role of ncRNAs in modulating the immune response in the brain microenvironment. More clinical studies are encouraged to assess the specificity and sensitivity of these ncRNAs.

Keywords: brain metastases with nsclc; csf biomarkers; isolated brain metastasis; lncrna; long non-coding rna; microrna; mirna; non-coding rna; serum biomarkers; solitary brain tumor metastases (sbms).

Figure 1. Regulation of gene expression by lncRNAs

(A) Long non-coding RNAs (lncRNAs) can bind to transcription factors and recruit them to the promoter locus to induce gene transcription. (B) LncRNAs can work as decoy molecules by binding to proteins regulating gene expression, such as transcription factors, subsequently suppressing gene expression. (C) LncRNAs can act as competitive endogenous RNAs (ceRNAs) by sponging microRNAs, preventing microRNAs from binding to and inhibiting messenger RNA (mRNA). (D) LncRNAs can act as scaffolding proteins by binding to other proteins, such as heterogeneous nuclear RNA (hnRNA), to make RNA-protein complexes (RNPs) that can activate gene expression by binding to a locus for gene promoter or repress gene expression by binding to gene repressors [6,11-15]. Image credit: Akram M. Eraky.