Application of LncRNA as A Biomarker in Cancer Diagnosis and Prognosis

Long non-coding RNA is a relatively good class of non-coding RNA (ncRNA) molecules that are involved in the regulation of various cellular processes, including transcription, intracellular transport and chromosome remodeling. Their disorders are related to the occurrence and development of various cancer types, and this fact makes them suitable as biomarkers for cancer diagnosis and prognosis. In recent years, detecting cancer-related lncRNAs in the body fluids of cancer patients has proven to be a particularly valuable method for effective cancer diagnosis. Compared with classic tumor biopsy, the diagnosis and prognosis of cancer using circulating lncRNA is preferred, especially because of their non-invasiveness and great potential for routine application in clinical practice.

One of the main advantages of making lncRNAs suitable as cancer diagnostic and prognostic biomarkers is their high stability when circulating in body fluids, especially when contained in exosomes or apoptotic bodies. Studies have shown that although there are a large number of ribonucleases in different body fluids, lncRNAs are still detected in these samples, and they can successfully resist the degrading activity of ribonuclease. In addition, in various body fluids, including whole blood, plasma, urine, saliva and gastric juice, it clearly reflects the imbalance of lncRNA in the primary tumor tissue.

These lncRNA features provide an opportunity to develop effective and convenient lncRNA-based biomarkers that are minimally invasive and, due to their relative non-invasiveness, may be better tolerated by patients compared to conventional biopsy. The detection of lncRNA related to circulating cancer in body fluids can be used for cancer assessment to distinguish early-stage tumor patients from healthy people with high sensitivity and specificity. In addition, it can also evaluate the prognosis of tumor patients, the risk of tumor metastasis and recurrence after surgery, and the success of surgery. For different types of cancers, several lncRNAs, alone or in combination, have shown diagnostic performance comparable to conventional cancer biomarkers, and even higher in some cases.

In order to introduce circulating lncRNA into clinical practice, further research and improvement should be carried out on the standardization of sample preparation protocols, the endogenous control of lncRNA in body fluids and the extraction methods, and the unified extraction methods should be used to evaluate the quality and reliability of lncRNA standards. The qPCR results should be more accurate and reliable, more high-quality research should be conducted, and selection bias should be minimized as much as possible. In addition, in order to reliably use circulating lncRNA as an effective cancer biomarker, some technical obstacles still need to be resolved and overcome in the future. Commercial kits using columns are mainly used to extract lncRNA from body fluids.

Unfortunately, consistent results have not been obtained regarding the difference in efficiency of column-based methods, indicating that comparison and standardization of lncRNA extraction methods are necessary. The absolute concentration of lncRNA in body fluids is usually low, and RNA amplification steps are often required before analysis, which is very time-consuming and can cause problems when fast results are required. It has also been observed that when using a NanoDrop spectrophotometer to quantify circulating RNA, RNA extracted from plasma and serum samples may not be detectable. This makes the development of highly sensitive methods for quantifying lncRNAs critical. Moreover, since the mechanism of lncRNA secretion is not fully understood, in addition to tumorigenesis, the level of circulating lncRNA may also be affected by other accompanying disease changes. Therefore, the overestimation of specific lncRNAs associated with specific diseases can be determined.

There are also some obstacles regarding the techniques commonly used to quantify circulating lncRNA. Quantitative RT-PCR is a recognized method for detecting and quantifying circulating RNA. However, the cost per sample is higher and the throughput of the method is lower. Recently developed detection methods, such as the lncRNA Profiler (System Biology Science SBI), which is related to human diseases, can measure a set of lncRNAs, but can only detect annotated lncRNAs.

lncRNA represents a relatively large heterogeneous group of ncRNA and is considered to be a suitable diagnostic and prognostic biomarker in cancer. In recent years, circulating lncRNA has proven to be extremely valuable for detecting various types of cancer. It is convenient to use them as biomarkers, not only because samples containing circulating lncRNA can be easily and non-invasively obtained from cancer patients, but also because these lncRNAs remain relatively stable in body fluids. By using various common molecular biology techniques, such as qRT-PCR, microarray hybridization and sequencing (such as RNA-seq), it can be easily detected in whole blood, plasma, serum, urine, saliva and gastric juice samples. Since the difference of lncRNAs in different body fluids is mainly dependent on the type of cancer, the current effective cancer diagnosis and prognosis depend on combining different candidate lncRNAs with previously established biomarkers. Some circulating lncRNAs have been shown to be promising and sensitive biomarkers.

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