The potential of circulating cell free RNA as a biomarker in cancer

ABSTRACT

Introduction: It is now clear that circulating cell-free ribonucleic acids (ccfRNAs), including messenger RNA (mRNA) and miRNA, are potential cancer biomarkers. As ccfmiRNA is relatively more stable than ccfmRNA, research should concentrate on developing novel methods to preserve the stability of ccfmRNA and standardization of the protocol which includes extraction, detection, and multicenter validation.

Areas covered: This literature review concentrates on the potential of ccfRNA being used as a biomarker in cancer, with special focus on mRNAs and microRNAs (miRNAs).

Expert opinion: With the advancement of high-throughput technologies such as RNA sequencing, a panel of biomarkers will be used for the diagnosis, prognosis and therapeutic monitoring of cancer patients. In order to achieve this important target, bioinformatics education to pathologists, scientists, and technologists in molecular diagnostic laboratories is essential. Moreover, the panel of these new ccfRNAs biomarkers has to obtain approval or clearance from an authority such as the US Food and Drug Administration (FDA), and the standard of utilizing these new protocols has to be recognized via accreditation exercise. Therefore, there is still a long way to go before an extensively use of ccfRNA biomarkers in cancer patients can be realized.

KEYWORDS:

• Circulating cell-free RNA
• messenger RNAs
• microRNAs
• noninvasive cancer screening
• molecular diagnosis
• cancer biomarkers

Article highlights

• Circulating RNAs are potential biomarkers in the diagnosis, prognosis and therapeutic efficacy of cancer patients.

• Many studies have demonstrated a correlation between ccfmRNA levels in serum and cancers, such as breast cancer and prostate cancer. However, the further development of potential ccfmRNA biomarkers is limited by cellular RNA contamination, relatively low abundance and instability of ccfmRNA.

• ccfmiRNA shows an association with various cancers, including chronic lymphocytic leukemia (CLL), prostate cancer, lung cancer, and colorectal cancer. Comparing to ccfmRNA, ccfmiRNA demonstrates a relatively better stability and readily-detectability by PCR-based methods.

• ccfRNA can provide important information on the expression of various target genes noninvasively without the need of biopsies. This breakthrough has enabled not only detection and monitoring of cancer, but also public health screening of pre-malignant disease.

• Real-time reverse transcription PCR is the gold standard for RNA quantification due to its high sensitivity and specificity. Recently, digital PCR has become a very useful molecular diagnostic technology which can provide a highly reproducible quantification of a very low abundance RNAs.

• NGS has high dynamic detection range, improved sensitivity, and reproducibility, ability to discover novel RNA and splicing variants, and quantification capability. However, limitations of deep sequencing include sequence-specific biases due to enzymatic ligation, high cost and demanding manpower.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.