Introduction:
Cancer is a malignant neoplastic disease that causes severe complications in individuals. Therefore an early diagnosis helps treat cancer at an early stage and avoids severe complications in individuals. Various diagnostic measures are used in cancer diagnosis, among which biopsy is considered the standard diagnostic method of a cancer diagnosis. In a biopsy, a small amount of tissue is removed from the tumor using a small needle, and the tissue sample is sent for pathological examination. It gives a definitive diagnosis by determining whether the cells related to the tumor are cancerous or not.
Due to recent advancements in biopsy, a type of non-invasive procedure known as liquid biopsy has been discovered. It has the potential to provide information about cancer using circulating biomarkers. The clinical application of the liquid biopsy procedure is still limited; however, many researchers are still researching liquid biopsy to expand its clinical application.
What Is Liquid Biopsy?
Liquid biopsy is a painless biopsy procedure that detects the presence of cancer markers in body fluids such as blood, urine, saliva, pleural effusions, and cerebrospinal fluid. It is also called fluid biopsy or fluid phase biopsy. In addition, it analyzes the molecular characteristics of a tumor that helps accurately detect any genetic alterations associated with cancer. Like traditional biopsy, it is also used primarily as a diagnostic tool in cancer. Besides diagnosis, it also helps in monitoring disease recurrence after treatment.
How Does a Liquid Biopsy Work?
Tumors release different biomolecules into the bloodstream that carry information about the tumor. These biomolecules can be detected by liquid biopsy, which helps in the molecular profiling of tumor cells. In a liquid biopsy, a small amount of body fluid, usually blood, is drawn from the patient's body, from which biomolecules like circulating tumor cells and circulating tumor DNA (ctDNA) are isolated and analyzed. A liquid biopsy helps in analyzing the following data that gives insights about a tumor, which includes;
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DNA (deoxyribonucleic acid) and chromosomal abnormalities.
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Protein and RNA (ribonucleic acid) expression.
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A point mutation (a genetic mutation where a nucleotide base is inserted, deleted, or changed from a DNA or RNA).
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Gene expression (a process by which information from a gene is used to produce RNA or protein).
What Are the Different Types of Liquid Biopsies?
The different types of liquid biopsy are categorized based on the type of material they analyze.
It includes;
1. Liquid Biopsy Analyzing Circulating Tumor Cells: Circulating tumor cells are cancer cells released from the primary tumor mass into the bloodstream. It makes up a small amount in the circulating blood, with one to ten circulating tumor cells per milliliters of whole blood. The presence of circulating tumor cells in the blood acts as metastatic agents resulting in tumor metastasis and recurrence.
Circulating tumor cells are cancer-specific, which helps identify the specific characteristics of tumor cells. The detection and analysis of circulating tumor cells through liquid biopsy help in early diagnosis, molecular phenotyping, assessing prognosis, evaluating treatment response, and disease monitoring.
2. Liquid Biopsy Analyzing Cell-Free DNA: Cell-free DNA is non-encapsulated DNA released by normal blood cells into the bloodstream. When cells from a tumor shed DNA, it is called circulating tumor DNA (ctDNA). The process of liquid biopsy analyzing circulating tumor DNA includes the following steps:
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The blood sample is taken from the patient and stored in preservation tubes.
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The blood sample is then taken to a laboratory, where plasma from the blood is isolated.
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The isolated plasma is stored at -80 degrees Celsius.
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Due to ctDNA instability, the ctDNA is extracted from plasma the same day using a QIAamp circulating nucleic acid on the QIAvac system.
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Followed by ctDNA extraction from plasma, pyrosequencing is done. Pyrosequencing helps detect any abnormalities in the DNA (mutations) associated with cancer.
Liquid biopsy analyzing circulating tumor DNA can measure the tumor load and help detect the mutations in multiple cancer types. For example, liquid biopsy analyzing circulating tumor DNA in lung cancer patients helps detect and monitor RASSF1A (Ras association domain family 1 isoform A) mutation.
3. Liquid Biopsy Analyzing Exosomal DNA: Exosomes are extracellular vesicles released into the body fluids by normal and cancer cells. In cancer, exosomes act as biological messengers that help stimulate cancer growth. It contains tumor-derived contents such as DNA, RNA, lipids, protein, and metabolites. Exosomes are a part of the disease process. Therefore, they can be used as a tumor biomarker in cancer diagnosis.
In addition, analyzing exosomal DNA using liquid biopsy can be used for molecular profiling, which helps detect any mutations in tumor cells.
What Are the Clinical Applications of Liquid Biopsies?
The clinical application of liquid biopsy includes;
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Assess disease prognosis.
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Determine the appropriate treatment plan for the patients.
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Measure how well cancer responds to the treatment.
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Monitor cancer recurrence after treatment.
What Are the Differences Between Liquid Biopsy and Tissue Biopsy?
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Liquid biopsy is a non-invasive technique, whereas tissue biopsy is an invasive procedure.
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Liquid biopsy causes no complications in individuals since it is a non-invasive procedure. Tissue biopsy is risky, and the complications depend on the site from where the tissue is removed.
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The possibility of performing continuous follow-up examinations is higher in liquid biopsy than in tissue biopsy.
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A liquid biopsy depicts a more comprehensive picture of the disease than a tissue biopsy.
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The results obtained from a liquid biopsy are faster than from a tissue biopsy.
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Liquid biopsy is less expensive than a tissue biopsy.
Conclusion:
Liquid biopsy is a promising cancer diagnostic tool that helps detect cancer at an early stage. Besides cancer diagnosis, it also helps assess prognosis, determines treatment plans, and monitors disease recurrence after treatment. The liquid biopsy holds distinct advantages over tissue biopsy, but still, tissue biopsy is used as a standard diagnostic tool in many cancers. However, many researchers are still trying to find new advancements in liquid biopsy to make it a standard diagnostic tool for different cancers.
