Increased gene expression of TIMP1 and CHI3L1 in fine‐needle aspiration biopsy samples from papillary thyroid cancer as compared to benign nodules

Abstract

Background Thyroid nodules are common ultrasound findings with malignancy rate 7%–15%. Our objective was to assess the relative expression of the tissue inhibitor of metalloproteinase‐1 gene (TIMP1) and chitinase‐3‐like protein 1 gene (CHI3L1) in fine‐needle aspiration biopsy (FNAB) washouts and the serum levels of their protein products (TIMP‐1 and chitinase‐3‐like protein 1 known as YKL‐40) in patients with papillary thyroid cancer (PTC) and patients with benign nodules. Furthermore, the correlation between gene expression and circulating protein product was evaluated. Methods Eighty patients who underwent FNAB in one tertiary center were recruited in the study. Forty with Bethesda V and VI nodules were operated and PTC was confirmed. The other 40 patients were with Bethesda II nodules. TIMP‐1 and YKL‐40 serum levels were measured in all subjects. The TIMP1 and CHI3L1 expression was assessed in FNAB washouts from 20 PTC patients and 20 benign cases using quantitative PCR. Results The relative expression of TIMP1 and CHI3L1 was significantly higher in the PTC group than in the benign group (p < .001 for TIMP1; p = .018 for CHI3L1). The PTC patients had higher serum TIMP‐1 than the patients with benign nodules (p = .036). We did not find significant difference in the YKL‐40 level between the two groups. TIMP1 and CHI3L1 expression did not correlate with the serum levels of their protein products. Conclusion FNAB washouts could be used for identification of diagnostic markers. The increased TIMP1 and CHI3L1 expression implies a role of these genes in the PTC carcinogenesis.

Proteomic analysis of radioiodine‑refractory differentiated thyroid cancer identifies CHI3L1 upregulation in association with dysfunction of the sodium‑iodine symporter

“…Previous studies have demonstrated that CHI3L1 is highly expressed in PTC compared with adjacent normal tissues ( 29 , 30 ), and it was further identified that CHI3L1 is significantly upregulated in RR-DTC compared with PTC in the present study. These findings suggest that CHI3L1 may serve an important role in thyroid cancer and could be associated with the dedifferentiation of tumor cells in RR-DTC.…”

Repurposing homoharringtonine for thyroid cancer treatment through TIMP1/FAK/PI3K/AKT signaling pathway

“… 28 Several studies found that the serum levels of TIMP1 are higher in the patients with DTC compared to the patients with benign nodule. 33 , 34 However, we did not evaluate the serum levels of TIMP1 of TC patients in the present study. Growing evidence suggests TIMP1 impacts on various cellular processes and regulates the initiation and progression in a wide range of cancers.…”