Table 1 Studies that were selected at the end of the search process

Heitzer, Ulz and Geigl (2015) [38]

To examine the use of cell-free DNA in liquid biopsy

Systematic review

The study reported that cell-free DNA is usually released from tumor locations and inflamed tissues as cells undergo necrosis or apoptosis. This form of tumor-derived DNA can be extracted from plasma and used to detect B-Raf proto-oncogene, KRAS, and serine/threonine kinase V600E mutations.

Molina-Vila et all. (2016) [14]

To examine the state of different cell operation and isolation techniques that have been used in liquid biopsy

Systematic review

The study reported that CTCs have played a key role in the management of cancer. In addition, the study showed that CTCs are used as critical pharmacodynamic and prognostic biomarkers for the management and diagnosis of cancer.

Torre et al. (2015) [16]

To review global cancer statistics

Systematic review

The researchers reported that the incidence and impact of cancer are more pronounced in developing nations than in developed countries. In addition, developing countries account for 57 and 65% of cancer cases and deaths worldwide.

Cronin et al. (2009) [18]

To examine the rates of breast cancer in the US

Systematic review

Cancer is a significant and common health problem affecting millions of Americans.

Mayo-de-Las-Casas et al. (2018) [19]

To examine methods for analyzing circulating free DNA

Systematic review

There are a wide range of methods and techniques for analyzing circulating free DNA.

Bettegowda et al. (2014) [20]

To explore the detection of circulating tumor DNA among patients with early and late malignancies

Systematic review

Liquid biopsy helps in detecting malignancies in the human body.

Braig et al. (2015) [21]

To explore the emergence and detection of epitope-changing mutations

Cohort study

Liquid biopsy can be used to detect EGFR G465R mutations.

Carvalho and Oliveira (2014) [22]

To identify biomarkers of cancer

Systematic review

Extracellular vesicles are critical markers of cancer.

Dawson, Rosenfeld, and Caldas (2013) [23]

To examine the role of circulating tumor DNA in cancer detection

Systematic review

Circulating tumor DNA is an important and reliable biomarker of metastatic breast cancer.

de Bruin et al. (2014) [24]

To examine the spatial and temporal genomic changes associated with non-small cell lung cancer

Systematic review

Non-small cell lung cancer was linked to intratumor heterogeneity in translocations, copy number alterations, and APOBEC cytidine deaminase activity.

Diaz et al. (2012) [25]

To examine whether KRAS DNA could be identified and detected in patients receiving a therapeutic anti-EGFR antibody

Longitudinal study

KRAS DNA was detected in 38% of the patients.

Crowley et al. (2013) [26]

To study how liquid biopsy can be used to detect and diagnose cancer

Systematic review

Liquid biopsy serves an effective tool for diagnosing cancer and analyzing the response to treatment.

Diaz et al. (2016) [27]

To explore the use of liquid biopsy in sensitive mutation detection

Longitudinal study

BEAMing and Safe-SeqS are effective in the detection of sensitive mutations among cancer patients.

Tu et al. (2016) [29]

To study the analytical strategies utilized in the assessment of oncogenic mutations

Systematic review

An EFIRM-based liquid biopsy can accurately detect oncogenic mutations.

El Messaoudi et al. (2013) [30]

To study the preanalytical parameters that affect ccfDNA concentration

Systematic review

The researchers determined an optimal preanalytical protocol that can be used in liquid biopsy procedures.

Janku et al. [2015] [31]

To compare mutations detected in plasma cfDNA and archival tissue

Cohort study

The outcomes were similar for the plasma cfDNA and archival tissue in 91% of the cases.

Liu et al. (2013) [32]

To study the diagnostic accuracy of pleural effusion and tumor tissue

Randomized control trial

MPE and plasma are effective materials for EGFR mutation detection in patients with lung cancer.

Brevet et al. (2011) [33]

To explore the use of spectrometry genotyping in EGFR mutations detection

Longitudinal study

Mass spectrometry genotyping is a feasible method for detecting EGFR mutations.

Zhao et al. (2013) [34]

To examine growth factor receptor mutation statuses in patients with lung cancer

Longitudinal study

Growth factor receptor mutations are critical indicators of lung cancer.

Lim et al. (2017) [35]

To explore the biomarkers of metastatic colorectal cancer

Systematic review

NRAS, KRAS, BRAF, PTEN, and PIK3CA were effective biomarkers of metastatic colorectal cancer.

Guttery et al. (2013) [40]

To identify the indicators of breast cancer

Systematic review

cfDNA and microRNA can be used to identify breast cancer.

O’Flaherty et al. (2012) [41]

To examine the clinical utility of circulating tumor cells

Systematic review

Circulating tumor cells can help in the diagnosis of lung cancer.

Mead et al. (2012) [42]

To study the biomarkers of normal colons, cancers, and benign polyps

Systematic review

Circulating tumor markers can help in the identification of normal colons, cancers, and benign polyps.

Zandberga et al. (2013) [43]

To study the prognostic, predictive and diagnostic values of cell-free microRNAs

Systematic review

Cell-free microRNAs can be used in predicting and diagnosing lung cancer.

Martinez-Galan et al. (2014) [45]

To analyze ER expression statuses in cancer patients

Longitudinal study

ESR1 influences estrogen receptor protein expression in patients with cancer.

Krebs et al. (2010) [36]

To explore the utility of circulating tumor cells in the management of cancer and predicting outcomes

Systematic review

Molecular characterization of the tumor cells provides a unique ability to assess and monitor the phenotypic and genotypic features of any cancer without the need to carry out an invasive biopsy. Thus, systems such as CellSearch, flow cytometry, immunofluorescence-based technologies, and reverse transcriptase PCR can help analyze tumor cells.

Regalado (2014) [37]

To examine how cancer can be spotted in a vial of blood taken from patients

Randomized controlled trial

Using a sample population of 846 patients suffering from 15 different cancer types, the researcher showed that analyzing tumor cells helped detect the presence of metastatic tumors in 80% of patients. Additionally, the researchers reported that the tumor cell analysis did not produce any false positives in the sample population.

Cree (2015) [39]

To examine the clinical utility as well as the cost-effectiveness of liquid biopsy in cancer treatment and management

Systematic review

Circulating tumor cells, circulating tumor DNA, and other protein markers enable caregivers to use liquid biopsy for the detection and monitoring of actionable RASSF1A mutations in patients with lung cancer.

Han, Wang, and Sun (2017) [44]

To examine the role of circulating tumor DNA as a biomarker in cancer detection

Systematic review

Circulating tumor DNA can be used to measure the tumor load and detect EGFR, PIK3CA, BRAF, KRAS, HER2, ALK, PDGFR, and KIT mutations in multiple cancer types, such as cancer of the lungs, pancreas, breast, prostate, and colorectal region. In addition, a considerable amount of research evidence supports that ctDNA can help in identifying mutations that are related to treatment choices with high specificity and sensitivity.

Piva (2015) [47]

To study the use of exomes in liquid biopsies

Systematic review

The researchers reported that exosomes have double-stranded DNA of the parent cells that can be analyzed in liquid biopsies.

Mayo-de-Las-Casas et al. (2017) [51]

To examine the role of liquid biopsy in the diagnosis and management of non-small cell lung cancer

Systematic review

miRNAs are non-coding types of RNA molecules that regulate the gene expression process. A single miRNA can influence the expression of several genes in the human body. Additionally, miRNAs are typically distributed throughout the entire human genome. However, most miRNAs are found in fragile sites that are quickly deleted by the existence of different types of cancers.

Spigal et al. (2016) [56]

To explore the total mutation burden in lung cancer and examine its relationship with the response to various PD-1/PD-L1-targeted therapies

Clinical trial

The assessment and monitoring of tumor mutations are very critical in the management of lung cancer. Mutations often lead to poor prognosis and high disease burden on patients.

Guibert et al. (2015) [58]

To explore KRAS mutations and their prognostic impact during treatment

Meta-analysis

The study revealed that higher levels of KRAS cfDNA allele mutations were correlated with poor responses to treatment. Thus, the collection of evidence related to cell mutations is critical in the treatment and monitoring of cancer [56, 57, 59].

Mardis and Wilson (2009) [60]

To explore the clinical significance and effectiveness of cancer genome sequencing

Systematic review

DNA sequencing with the Sanger method can identify structural variant loci, copy number, and focal mutations (such as small in/dels and single nucleotides) in the tumor genome.

Malapelle et al. (2016) [63]

To examine the use of next-generation sequencing techniques in liquid biopsies involving non-small cell lung cancer patients

Systematic review

The next-generation sequencing method, on the other hand, relies on the capillary electrophoresis technique to fragment genomic strands and identify bases in each fragment via emitted signals. The technique helps in the detection of ARID1A, SOX9, FAM123B, ATM KRAS, PIK3C, and TP53 mutations.

Østrup et al. (2017) [64]

To examine the use of a liquid biopsy to determine somatic copy number alterations (SCNAs)

Clinical trial

The study showed that the somatic number of alterations that occur in tumors provide critical information on tumor classification, treatment targets, and patient responses to cancer treatment interventions, such as chemotherapy. Thus, copy number alterations can be assessed using plasma samples that contain cell-free tumor DNA (ccfDNA).

Wang et al. (2017) [65]

To explore the use of liquid biopsy in the detection of early- and late-stage human malignancies

Cohort study

A liquid biopsy is a less invasive test that can frequently be performed with less morbidity than conventional biopsies [65]. This feature is of great importance when healthcare practitioners want to provide temporal measurements of the tumor burden and analyze the possibility of recurrence and malignancy.