No abstract

Thyroid cancer is among the most common endocrine malignancies, with papillary thyroid cancer (PTC) accounting for approximately 80% of new thyroid cancer cases in 2017 (ACS). Despite the high sensitivity (95%) of ultrasound-guided fine needle aspiration biopsies (FNAB), approximately 20% of FNA biopsies are indeterminate, which require resection, despite the fact that about 50% are benign. The outcome is that many patients undergo surgical resection of benign disease resulting in avoidable iatrogenic morbidity, and about $700 million in health care costs. Thus, identifying diagnostic/prognostic molecular signatures of PTC would greatly reduce the number of costly, unnecessary resections following indeterminate biopsies. Following consenting of NYEEI patients, surgery, and diagnosis by the pathologist, RNA was prepared from PTC and matched-normal tissue samples, rRNA eliminated and RNA-Seq performed (100bp, paired-end). STARv2.5.2b/ htseq-countv0.6.1 and DESeq2 were used to align raw sequences, and measure transcript abundance. Preliminary bioinformatics analysis was performed with Advaita's iPathway Software. Over 1500 protein-coding transcripts, and 386 lincRNAs achieved 1.5 fold level differential expression (p= 0.05). Gene Ontology enrichment analysis indicated that locomotion, cell motility, signaling, cell differentiation and cell communication were among the most statistically significantly biological processes altered between PTC and matched-normal tissue. Cytokine, signal transducer, ion channel activity, receptor and growth factor activities were among the most statistically significantly molecular functions altered between PTC and matched, normal tissue. Additionally, Pathway Analysis indicated that cell adhesion molecules, cytokine-cytokine receptor, ECM-receptor, cancer, proteoglycans and Jak-Stat signaling were significantly altered. Linc01614, linc00475, linc01510, RP11-244M2.1, linc00511, linc01314 and linc00973 were the most overexpressed lncRNAs. Patients who had lymph node metastasis showed differential expression compare to patients with localized disease. These same patients had statistically significantly alterations in the negative regulation of adhesion-dependent cell spreading and cell-matrix adhesion, establishment of cell polarity, and protein kinase C signaling according to Gene Ontology enrichment analysis. In addition to capturing protein coding transcripts, our RNA processing technique has enriched our RNASeq database for novel, noncoding RNAs that are known to play critical roles in cell homeostasis. The biological significance of differentially expressed RNA transcripts is currently being investigated. We anticipate that the detailed bioinformatics analysis of our coding and noncoding databases will yield new diagnostic/prognostic biomarkers, and therapeutic targets. Citation Format: Sina Dadafarin, Anvita Gupta, Katharine Dermigny, Melanie Jones, Timmy O'Connell, JK Rasamny, Nina Suslina, Iacob Iacob, Monica Schwarcz,, Ameet Kamat, Cameron Budenz, Craig Berzofsky, Deya Jourdy, Tali Lando, Stimson Schantz, Sarnath Singh, Edward Shin, Augustine Moscatello, Raj Tiwari, Jan Geliebter. Coding and non-coding RNA in papillary thyroid cancer - markers for disease progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2469.

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No abstract

Thyroid cancer is among the most common endocrine malignancies, with papillary thyroid cancer (PTC) accounting for approximately 80% of new thyroid cancer cases in 2017 (ACS). Despite the high sensitivity (95%) of ultrasound-guided fine needle aspiration biopsies (FNAB), approximately 20% of FNA biopsies are indeterminate, which require resection, despite the fact that about 50% are benign. The outcome is that many patients undergo surgical resection of benign disease resulting in avoidable iatrogenic morbidity, and about $700 million in health care costs. Thus, identifying diagnostic/prognostic molecular signatures of PTC would greatly reduce the number of costly, unnecessary resections following indeterminate biopsies. Following consenting of NYEEI patients, surgery, and diagnosis by the pathologist, RNA was prepared from PTC and matched-normal tissue samples, rRNA eliminated and RNA-Seq performed (100bp, paired-end). STARv2.5.2b/ htseq-countv0.6.1 and DESeq2 were used to align raw sequences, and measure transcript abundance. Preliminary bioinformatics analysis was performed with Advaita's iPathway Software. Over 1500 protein-coding transcripts, and 386 lincRNAs achieved 1.5 fold level differential expression (p= 0.05). Gene Ontology enrichment analysis indicated that locomotion, cell motility, signaling, cell differentiation and cell communication were among the most statistically significantly biological processes altered between PTC and matched-normal tissue. Cytokine, signal transducer, ion channel activity, receptor and growth factor activities were among the most statistically significantly molecular functions altered between PTC and matched, normal tissue. Additionally, Pathway Analysis indicated that cell adhesion molecules, cytokine-cytokine receptor, ECM-receptor, cancer, proteoglycans and Jak-Stat signaling were significantly altered. Thyroid differentiation scores (TDS) were calculated for each patients and correlations between differentially expressed lincRNA’s and the TDS were identified. We expect followup experiments modulating the expression of lincRNAs most strongly correlated to the TDS will augment the expression of iodine-handling genes and differentiation in PTC cell lines. We anticipate that the detailed bioinformatics analysis of our coding and noncoding databases in addition to evidence from in vitro studies will yield new diagnostic/prognostic biomarkers, and therapeutic targets. Citation Format: Sina Dadafarin, Anvita Gupta, Katharine Dermigny, Leyla Cavdar, Brandon Pecchia, Melanie Jones, Timmy O'Connell, JK Rasamny, Nina Suslina, Codrin Iacob, Monica Schwarcz, Ameet Kamat, Cameron Budenz, Craig Berzofsky, Deya Jourdy, Tali Lando, Stimson Schantz, Sarnath Singh, Edward Shin, Augustine Moscatello, Raj Tiwari, Jan Geliebter. Investigating coding and non-coding RNA in papillary thyroid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3570.