Other efficient body fluids used for liquid biopsy

In addition to blood, several other body fluids such as urine[7], saliva[8], pleural effusions, and cerebrospinal fluid (CSF), as well as stool, have been shown to contain tumor-derived genetic material, and our ability to exploit liquid biopsies for diagnostic purposes will further expand in the future. The analysis of liquid biopsy specimens is, however, challenging because ctDNA is fragmented and highly under represented compared with germ line cfDNA, and only a limited number of CTCs can be isolated from a blood sample. Several studies have revealed the presence of tumor-derived nucleic acids in other body fluids, such as urine, saliva and CSF. The localization of the primary tumor and of any metastatic lesions seems to have a major effect on the abundance of ctDNA in different body fluids [1].

Urine is a valuable source of ctDNA for urogenital cancers, such as prostate, bladder, and cervical cancers, and nonurogenital malignancies, such as NSCLC, CRC, and gastric cancer [2]. The first liquid biopsy test on urine, the Progensa1 PCA3 Assay, was FDA approved in 2012 to aid the decision-making of a repeat prostate biopsy in case of a first negative biopsy. This test measures the level of prostate cancer antigen 3 (PCA3) lncRNA, which is increased in >95% of primary prostate tumors [3].

Salivary biomarkers include ctDNA for head and neck squamous cell carcinoma [4], and miRNAs for detecting early malignancy in potentially malignant oral cancers [5].

Cerebrospinal fluid (CSF), as a result of its direct contact with the central nervous system (CNS), is set to become an important source of biomarkers for CNS-restricted cancers, potentially overcoming the relative scarcity of circulating biomarkers (especially ctDNA) in these diseases caused by the blood–brain barrier [6]. CSF-derived ctDNA has proven to represent genetic alterations of brain tumors better than plasma ctDNA [7].

The analysis of stool-derived DNA was recently validated as a powerful diagnostic tool for CRC [8].

sputum DNA and protein content have potential in the context of lung cancer [9]. Pleural effusions are also sources of DNA biomarkers for lung cancer [10]

Reference

[1]        Giulia Siravegna, et al. (2017) Integrating liquid biopsies into the management of cancerf. Nautre Reviews. Clinical Oncology 14, 531-548

[2]        Lu, T. and Li, J. (2017) Clinical applications of urinary cell-free DNA in cancer: current insights and promising future. Am. J. Cancer Res. 7, 2318–2332

[3]        Durand, X. et al. (2011) Progensa PCA3 test for prostate cancer. Expert Rev. Mol. Diagn. 11, 137–144

[4]        Cao, Y. et al. (2018) Methylated genomic loci encoding microRNA as a biomarker panel in tissue and saliva for head and neck squamous cell carcinoma. Clin. Epigenet. 10, 43 

[5]        Maheswari, T.N.U. et al. (2018) Salivary micro RNA as a potential biomarker in oral potentially malignant disorders: a systematic review. Ci Ji Yi Xue Za Zhi 30, 55–60 

[6]        Bettegowda, C. et al. (2014) Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci. Transl. Med. 6, 224ra24 

[7]        De Mattos-Arruda, L. et al. (2015) Cerebrospinal fluid-derived circulating tumor DNA better represents the genomic alterations of brain tumors than plasma. Nat. Commun. 6, 8839 

[8]        Kisiel, J.B. et al. (2018) Analysis of DNA methylation at specific loci in stool samples detects colorectal cancer and high-grade dysplasia in patients with inflammatory bowel disease. Clin. Gastroenterol. Hepatol. Published online May 15, 2018. http://dx.doi.org/10.1016/j.cgh.2018.05.004

[9]        Rangel, M.P. et al. (2018) Detection of sputum cofilin-1 as indicator of malignancy. Braz. J. Med. Biol. Res. 51, e7138 

[10]      Yeo, C.D. et al. (2013) Detection and comparison of EGFR mutations in matched tumor tissues, cell blocks, pleural effusions, and sera from patients with NSCLC with malignant pleural effusion, by PNA clamping and direct sequencing. Lung Cancer 81, 207–212