Extracellular RNAs as Biomarkers for Cancer

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Extracellular RNAs as Biomarkers for Cancer

Extracellular RNAs (exRNAs) are a type of RNA molecules that exist in all human body fluids including saliva, urine, blood plasma and serum. At first, exRNAs were thought to only have ribonuclease activity to degrade foreign RNA molecules, especially double-stranded RNA viruses and they were easy to be degraded in circulation. However, with the development of RNA extraction, purification, sequencing and data analysis, it has been revealed that exRNAs are stable and complex molecules with multiple biological functions. As various types of cells and tissues including cancers can secrete exRNAs, many researches have focused on exRNA as a biomarker reflecting physiologic and/or pathologic states of patients.

Extracellular RNAs as Biomarkers for CancerFigure 1. Biogenesis and communication of exRNAs. (Kim S, et al., 2020)

exRNA as Biomarkers for Cancer

The presence of exRNAs from cancer cells in biofluids provides the potential for their application as biomarkers to provide a "snapshot" of the macromolecular composition of tumor cells. Cancer diagnosis, treatment decisions, longitudinal profiling of dynamic genetic changes in tumors, stratification for clinical trials, outcomes of clinical trials, and follow-up for populations at risk, all have the potential to be informed by exRNA assays on biofluids, thereby, tumor biopsy is not required in many cases. exRNA-based assays could also provide an important companion diagnostic to identify specific pathways mutated or altered in individual cancers. As cancer molecular diagnostics becomes more and more complex, knowledge about specific abnormal pathways on a patient-by-patient basis could provide specific drug targeting opportunities for individualized care.

exRNAs are ideal biomarkers because of their highly sensitive, predictive, translatable, robust and most importantly minimally invasive. The application of exRNAs in biofluids as biomarkers of cancer is being explored using many different biofluids and types of cancer with analysis of levels and mRNA mutations, as well as levels of miRNAs and other non-coding RNAs.

Table 1. Cancer extracellular RNA (exRNA) biomarkers.

Cancers by Body SystemCancer TypeBiomarker NameRNA TypeUp/DownValueSource
Genitourinary systemProstate cancerhTERTmRNAUpDiagnosisPeripheral blood
Genitourinary systemProstate cancerPCA3lncRNAUpDiagnosisUrine
Digestive systemGastric cancerpiR-651piwiRNADownDiagnosisPeripheral blood
Digestive systemGastric cancerpiR-823piwiRNADownDiagnosisPeripheral blood
Digestive systemOral cancermiR-125amiRNADownDiagnosisSaliva
Digestive systemOral cancermiR-200amiRNADownDiagnosisSaliva
Digestive systemLiver cancermiR-18amiRNAUpDiagnosisSerum exosome
Digestive systemLiver cancermiR-221miRNAUpDiagnosisSerum exosome
Digestive systemLiver cancermiR-222miRNAUpDiagnosisSerum exosome
Digestive systemLiver cancermiR-224miRNAUpDiagnosisSerum exosome
Respiratory systemNon-small-cell lung cancermiR-193b,
miR-301,
miR-141,
miR-200b
miRNADiagnosisSerum
Respiratory systemNon-small-cell lung cancerSNORD33,
SNORD66,
SNORD76
snoRNAUpDiagnosisPlasma
Nervous systemGlioblastoma and brain metastasismiR-10bmiRNAUpDiagnosisCerebrospinal fluid
Nervous systemGlioblastoma and brain metastasismiR-21miRNAUpDiagnosisCerebrospinal fluid

Identification of Novel exRNA Biomarkers

More exRNAs continue to be found as potential biomarkers. For example, as important parts of splicing machinery, U2 snRNAs' fragments were found in blood, suggesting altered abundance in mice when implanted with several human cancer types. Circular RNAs (CircRNAs) were found to stably exist in exosomes and differentially expressed between cancer and normal serum, making a potential source of biomarkers as well. Discovery of novel RNA biomarkers in cell-free fluids requires the preparation of RNA samples and libraries, data generation with quantified methods, and correlation with diagnostic or prognostic characteristics by using bioinformatics analysis.

Experimental and analytical procedures for identifying novel RNA biomarkers:

  • Tissues and/or bio-fluids are collected from both patients and healthy individuals;
  • RT-qPCR, small RNA sequencing, or other RNA sequencing methods are performed on isolated and purified RNA samples;
  • The collected quantification data would go through bioinformatics and statistical analysis;
  • The differential expression of selected RNA biomarkers should be validated by RT-qPCR.

As a global biotechnology company specializing in RNA research, IntegrateRNA offers a wide range of services to support you in the discovery of exRNA biomarkers. Whether you are doing basic research on model organisms or conducting preclinical or clinical studies, you can count on our in-depth experience and expertise to make your project a success. If you have any questions, please feel free to contact us.

References:

  1. Rennert R C, et al. ExRNA in biofluids as biomarkers for brain tumors[J]. Cellular and molecular neurobiology, 2016, 36(3): 353-360.
  2. Kim S, et al. Extracellular RNA: Emerging roles in cancer cell communication and biomarkers. Cancer Letters, 2020, 495: 33-40.
  3. Redzic J S, et al. Extracellular RNA mediates and marks cancer progression//Seminars in cancer biology. Academic Press, 2014, 28: 14-23.
  4. Lee H J. Microbial extracellular RNAs and their roles in human diseases. Experimental Biology and Medicine, 2020: 1535370220923585.
  5. Xi X, et al. RNA biomarkers: frontier of precision medicine for cancer. Non-coding RNA, 2017, 3(1): 9.
For research use only. Not intended for any clinical use.
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