Ribonucleic acid or RNA is a molecule essential for various functions within our cells. While DNA contains the genetic blueprint, RNA helps decode and carry out those instructions. In recent years, researchers have discovered that analyzing different types of RNA molecules can provide valuable biomarkers for disease detection and diagnosis. This article discusses some of the major RNA markers being studied and their potential clinical applications.
Messenger RNA or mRNA is responsible for carrying the instructions from DNA for producing proteins. Analyzing mRNA expression levels can give insights into biological processes and disease states. Changes in mRNA levels of certain genes have shown promise as biomarkers for cancer and other conditions. For example, increased levels of prostate-specific membrane antigen (PSMA) mRNA have been linked to prostate cancer progression and aggressiveness. Researchers are exploring panels of mRNA biomarkers from tissue and blood samples for non-invasive cancer screening and diagnosis. Large-scale profiling of mRNA expression is also providing clues about novel disease subtypes and personalized treatment strategies.
MicroRNAs or miRNAS are short, non-coding RNA molecules that regulate gene expression at the post-transcriptional level. Their dysregulation has been implicated in various diseases. Certain miRNA expression signatures have demonstrated potential as clinical biomarkers. For instance, elevated levels of circulating miR-21 have been found in patients with ovarian cancer, colorectal cancer, and other malignancies. miR-141 and miR-375 show potential as biomarkers for the detection of prostate cancer. Studies indicate miRNA signatures from blood and other biofluids could provide cheap, minimally invasive options for cancer screening and monitoring. Researchers are optimistic that miRNA biomarkers may transform strategies for early cancer detection in the future.
Long non-coding RNAs or lncRNAs are a newer class of non-coding RNAs greater than 200 nucleotides in length. They are involved in important cellular processes like epigenetic regulation, genomic imprinting, and disease pathogenesis. Alterations in lncRNA expression have been linked to cancer and other pathological conditions. For example, higher levels of the lncRNA HOTAIR predict poor prognosis in breast, liver, and gastrointestinal cancers. DOWNSTREAM OF PRC1 (DPC4-AS1) is overexpressed in esophageal cancer and shows promise as a biomarker. Researchers believe identifying unique lncRNA expression fingerprints could lead to breakthrough diagnostic and prognostic biomarkers with clinical utility.
Circulating RNA Biomarkers
Various RNA species can be detected in body fluids like blood, urine, and saliva, offering a less invasive approach for biomarker development. Circulating tumor RNA (ctRNA) shed from primary and metastatic tumor cells shows potential for non-invasive cancer monitoring. For instance, increased levels of prostatic acid phosphatase (PAP) mRNA in blood are indicative of prostate cancer recurrence. Cell-free MicroRNAs are also stable in the bloodstream, protected within extracellular vesicles. Researchers are investigating ctRNA-based liquid biopsy approaches for improving cancer management in areas such as early detection, recurrence monitoring, and treatment response assessment. However, technical challenges regarding optimal extraction, amplification, and analytical methods need to be addressed before clinical application.
RNA Biomarkers in Precision Medicine
As researchers gain a deeper understanding of RNA biomarkers associated with disease risk, progression, and drug response; their clinical utility is expanding in precision medicine. For example, expression of thymidylate synthase (TS) mRNA predicts response to 5-FU chemotherapy in colorectal cancer patients. Low ESR1 mRNA levels indicate resistance to tamoxifen in breast cancer. Genetic variation in miRNA binding-sites also influences drug efficacy. It is hoped that multi-analyte RNA profiling studies will enable development of diagnostic tests for personalized treatment selection and monitoring in the future. This could potentially revolutionize disease management approaches through tailoring of therapies based on patients' molecular profiles.
In summary, various RNA species show great potential as non-invasive biomarkers with applications in cancer screening, diagnosis, prognosis, and precision medicine. Large-scale clinical validation studies are needed before RNA markers can be translated into routine clinical use. Technological advancements are also required to address pre-analytical and analytical challenges in biomarker development pipelines. With further research, RNA biomarkers hold promise to transform healthcare by enabling early disease detection and personalized treatment approaches.