Abstract 767: Role of COL26A1 in papillary thyroid cancer invasion

Abstract

Papillary thyroid cancer (PTC) accounts for 70-80% of all thyroid cancer cases and has been increasing in incidence over the last few decades. It is now the 8th most common cancer in women in the United States and the most common cancer in women under 25 years of age. PTC is often curable, as the tumors are most often slow-growing and surgically resectable and lymphatic spread does not worsen the generally favorable prognosis. However, there are aggressive forms of PTC that are not adequately treated by current therapeutic modalities and invasion into surrounding tissue next to the thyroid worsens the prognosis. Utilizing the NYMC biobank of PTC patient samples, meta-analysis of RNASeq data was performed, ranking differentially expressed genes between invasive vs noninvasive and lymph node positive vs lymph node negative samples. These genes were analyzed in conjunction with the GDC’s The Cancer Genome Atlas (TCGA) Thyroid Cancer (THCA) study, in which the Kaplan Meier survival curve identified genes with a significant impact on survival and those that were increased in metastatic tissue samples. Of the top differentially expressed genes that were increased in patients with extrathyroidal extension and lymph node metastasis, COL26A1 significantly inversely associated with survival (p = 0.0086). COL26A1 codes for collagen type XXVI α1 chain with known roles in degradation of the ECM and collagen chain trimerization. In TCGA datasets, COL26A1 expression was significantly correlated with clinical attributes including MACIS score (q = .001), differentiation score (q = 0.025), and tumor stage (q = 0.025). COL26A1 expression was increased 3-fold in papillary thyroid cancer cell line K1 when compared to normal thyroid cancer cells, NThy-ori 3-1. Two CRISPR guides designed to target COL26A1 were introduced into K1 resulting in repression of COL26A1 by 50% in both knockdowns. COL26A1 repression decreased the proliferation (33%), tumorigenicity (86%), invasion (33%), and migration capacity (73%). Furthermore, knockdown of COL26A1 leads to decreased cell-to-cell adhesion in culture. Thus, COL26A1 may have potential use as a prognostic marker and actionable therapeutic target for small molecule inhibitors. Long noncoding RNAs (lncRNAs) have vast implications in different cancer types with roles in gene expression via modulation of coding and noncoding RNAs. lncRNAs are tissue- and stage- specific and stable in serum alluding to their ability to be used in thyroid cancer prognosis and diagnosis. Therefore, we investigated the mRNA-miRNA-lncRNA axis involved in regulation of COL26A1 utilizing Qiagen Ingenuity Pathway Analysis (IPA). We have identified potential pathways linking COL26A1 with PTC, highlighting those involved in proliferation, migration, invasion, and adhesion. Investigation into these molecular interactions and pathways can elucidate the role of COL26A1 and allow for its optimal targeting for treatment of invasive papillary thyroid cancer. Citation Format: Michelle Carnazza, Danielle Quaranto, Nicole DeSouza, Sina Dadafarin, Augustine Moscatello, Raj K. Tiwari, Jan Geliebter. Role of COL26A1 in papillary thyroid cancer invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 767.