**4. Follicular thyroid cancer and liquid biopsy**

Follicular thyroid carcinoma (FTC) is the second most common type of thyroid cancer, comprising 10–15% of all thyroid carcinomas [4, 13, 31]. Although FTC is the second most common type, its incidence has decreased over the past few years [31]. World Health Organization has defined FTC as a malignant epithelial tumor showing follicular cell differentiation in which the diagnostic nuclear features of PTC are absent. Lesions are usually encapsulated and show invasive growth pattern [14]. The diagnosis of FTC is a difficult dilemma in cases when capsular, vascular, or extrathyroidal invasion or metastasizing is not straightforward [32, 33]. A lot of studies have researched biomarkers in liquid biopsy for PTC; however, limited amount of information is found about FTC. One of those studies explored miRNA dysregulation and tried to found miRNA markers for diagnostic purposes in the case of FTC [34]. Dettmer with colleagues found upregulation of miR-182/-183/-221/-222/-125a-3p and a downregulation of miR-542-5p/-574-3p/-455/-199a. They concluded that distinction between FTC and hyperplastic nodules can be done by the use of dysregulated miRNA in the tissues. The miRNAs found


**6. Anaplastic thyroid cancer and liquid biopsy**

This process enables cells to migrate and invade [26–28].

thyroid cancer cells, which enhances cell proliferation [26–28].

Downregulated in

Downregulated in

Downregulated in

cells

cells

miR-138 Downregulated in cells

cells

ferentiated follicular thyroid cells [14].

**Diagnosis Type of** 

Anaplastic thyroid cancer **miRNA**

miR-30 family

miR-125a, miR-125b

miR-200 family

miR-17-92 cluster

miR-146a, miR-146b

miR-221, miR-222

**Table 4.** Expression of microRNA in ATC.

Anaplastic thyroid carcinoma (ATC) is aggressive thyroid tumor which consists of undif-

Many miRNAs have been found to be dysregulated in thyroid cancer, but only a few miRNAs are exclusively dysregulated in anaplastic thyroid cancer (ATC) [28]. Loss of miR-200 expression in ATC results in epithelial-mesenchymal transition (EMT) that represses the epithelial features of cancer cells and disrupts the cell-cell adhesion mediated by the loss of E-cadherin.

Overexpression of the miR-17-92 cluster results in downregulation of tumor suppressor PTEN. This process potentiates the activation of AKT/mTOR growth and survival signaling. Another important tumor-suppressive pathway targeted by miR-17-92 is the TGFβ signaling pathway [28]. Increase of miR-17-92 leads to a loss of the tumor inhibitory effect of TGFβ in

**Type of regulation Outcome References**

Increase with the progression of histological dedifferentiation and malignant behavior

Increase the invasive potential of tumor

differentiation and invasion

Upregulated in cells Promote tumor growth and invasion

Upregulated in cells Promote tumor growth and invasion

invasion

Upregulated in cells Dysregulated cell

miR-4295 Upregulated in cells Increased cell migration and

Protect cancer cells from apoptosis and autophagy

Promote tumor invasion Sasanakietkul et al. [26]

Sasanakietkul et al. [26] Rodriguez-Rodero et al. [27] Boufraqech et al. [28]

Liquid Biopsy in Patients with Thyroid Carcinoma http://dx.doi.org/10.5772/intechopen.85356 93

Sasanakietkul et al. [26] Rodriguez-Rodero et al. [27]

Sasanakietkul et al. [26] Rodriguez-Rodero et al. [27] Boufraqech et al. [28]

Sasanakietkul et al. [26] Rodriguez-Rodero et al. [27] Boufraqech et al. [28]

Rodriguez-Rodero et al. [27] Sasanakietkul et al. [26]

Rodriguez-Rodero et al. [27] Sasanakietkul et al. [26]

Rodriguez-Rodero et al. [27] Sasanakietkul et al. [26]

**Table 2.** Expression of microRNA in FTC.

in follicular thyroid cancers (FTC) are also frequently present in other subtypes of thyroid cancer [27]. miR-199a-5p is downregulated, but miR-197 and miR-346 are upregulated in FTC leading to increased cancer cell proliferation [28] (**Table 2**).
