Overexpression of chitinase‐3‐like protein 1 is associated with structural recurrence in patients with differentiated thyroid cancer

Abstract

We previously identified that the expression of chitinase‐3‐like protein 1 (CHI3L1) was upregulated during thyroid cancer progression. Here, we investigated the prognostic significance of CHI3L1 expression in thyroid neoplasms and examined the potential oncogenic roles. CHI3L1 immunochemical staining was performed on tissue microarrays of benign and malignant thyroid tumours. Compared with normal thyroid tissue and benign thyroid lesions that had low or no detectable CHI3L1 expression, CHI3L1 was overexpressed in both differentiated and undifferentiated thyroid cancer. High CHI3L1 expression was associated with extrathyroidal extension, lymph node metastasis, and shorter recurrence‐free survival in differentiated thyroid cancer. The biological roles of CHI3L1 were further investigated by gain‐ and loss‐of‐function assays. CHI3L1 silencing suppressed clonogenicity, migration, invasion, anoikis resistance, and angiogenesis in thyroid cancer cells, although exogenous CHI3L1 treatment promoted these malignant phenotypes. Cysteine‐rich angiogenic inducer 61 (CYR61) was identified as a downstream target of CHI3L1 by RNA‐seq analysis. CYR61 silencing or treatment reversed the alterations induced by CHI3L1 modulation. Our results demonstrate that CHI3L1 is overexpressed in thyroid cancer and is associated with an increased risk of disease recurrence. Additionally, CYR61 may participate in CHI3L1‐mediated tumour progression. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Biomarkers, Master Regulators and Genomic Fabric Remodeling in a Case of Papillary Thyroid Carcinoma

“…A high expression of NPC2 and its significant elevation in PTC were also detected in meta-analyses of public PTC transcriptomes [28]. Overexpression of CHI3L1, the most up-regulated gene in the analyzed PTC, was reported as associated with metastatic PTC [29] and its recurrence [30]. Significantly decreased expression of TFF3, the most down-regulated gene in our study, was also reported in several other studies (e.g., [31]).…”

Biomarkers, Master Regulators and Genomic Fabric Remodeling in a Case of Papillary Thyroid Carcinoma

“…High expression of NPC2 and its significant elevation in PTC were also detected in meta-analyses of public PTC transcriptomes [20]. Overexpression of CHI3L1, the most up-regulated gene in the analyzed PTC, was reported as associated with metastatic PTC [21] and its recurrence [22]. Significantly decreased expression of TFF3, the most down-regulated gene in our study, was also reported in several other studies (e.g.…”

Long Non-Coding RNA MAPK8IP1P2 Inhibits Lymphatic Metastasis of Thyroid Cancer by Activating Hippo Signaling via Sponging miR-146b-3p

“…Several lines of evidence have reported the pivotal role of anoikis resistance in lymphatic metastasis of cancer ( 10 , 11 ), even in lymphatic metastasis of thyroid cancer ( 18 – 20 ). Furthermore, anoikis resistance was reported to be significantly correlated with positive lymph node metastasis in various cancers ( 12 – 17 ).…”

“…In several cancer scenario, anoikis resistance correlated significantly with positive lymph node metastasis status, including esophageal carcinoma ( 12 , 13 ), melanoma ( 14 ), tongue cancer ( 15 ), breast cancer ( 16 ), and colorectal cancer ( 17 ). Importantly, development of anoikis resistance has been reported to significantly contribute to lymphatic metastasis of thyroid cancer ( 18 – 20 ). Therefore, investigating the underlying mechanism of anoikis resistance in lymphatic metastasis of thyroid cancer is of great necessity.…”