scholarly journals Transcriptome analysis discloses dysregulated genes in normal appearing tumor-adjacent thyroid tissues from patients with papillary thyroid carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Huiling He ◽  
Sandya Liyanarachchi ◽  
Wei Li ◽  
Daniel F. Comiskey ◽  
Pearlly Yan ◽  
...  

AbstractPapillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. The molecular characteristics of histologically normal appearing tissue adjacent to the tumor (NAT) from PTC patients are not well characterized. The aim of this study was to characterize the global gene expression profile of NAT and compare it with those of normal and tumor thyroid tissues. We performed total RNA sequencing with fresh frozen thyroid tissues from a cohort of three categories of samples including NAT, normal thyroid (N), and PTC tumor (T). Transcriptome analysis shows that NAT presents a unique gene expression profile, which was not associated with sex or the presence of lymphocytic thyroiditis. Among the differentially expressed genes (DEGs) of NAT vs N, 256 coding genes and 5 noncoding genes have been reported as cancer genes involved in cell proliferation, apoptosis, and/or tumorigenesis. Bioinformatics analysis with Ingenuity Pathway Analysis software revealed that “Cancer, Organismal Injury and Abnormalities, Cellular Response to Therapeutics, and Cellular Movement” were major dysregulated pathways in the NAT tissues. This study provides improved insight into the complexity of gene expression changes in the thyroid glands of patients with PTC.

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1597 ◽  
Author(s):  
Dagmara Rusinek ◽  
Aleksandra Pfeifer ◽  
Marta Cieslicka ◽  
Malgorzata Kowalska ◽  
Agnieszka Pawlaczek ◽  
...  

Background: Telomerase reverse transcriptase promoter (TERTp) mutations are related to a worse prognosis in various malignancies, including papillary thyroid carcinoma (PTC). Since mechanisms responsible for the poorer outcome of TERTp(+) patients are still unknown, searching for molecular consequences of TERTp mutations in PTC was the aim of our study. Methods: The studied cohort consisted of 54 PTCs, among them 24 cases with distant metastases. BRAF V600E, RAS, and TERTp mutational status was evaluated in all cases. Differences in gene expression profile between TERTp(+) and TERTp(−) PTCs were examined using microarrays. The evaluation of signaling pathways and gene ontology was based on the Gene Set Enrichment Analysis. Results: Fifty-nine percent (32/54) of analyzed PTCs were positive for at least one mutation: 27 were BRAF(+), among them eight were TERTp(+), and 1 NRAS(+), whereas five other samples harbored RAS mutations. Expression of four genes significantly differed in BRAF(+)TERTp(+) and BRAF(+)TERTp(−) PTCs. Deregulation of pathways involved in key cell processes was observed. Conclusions: TERTp mutations are related to higher PTC aggressiveness. CRABP2 gene was validated as associated with TERTp mutations. However, its potential use in diagnostics or risk stratification in PTC patients needs further studies.


Molecules ◽  
2014 ◽  
Vol 19 (8) ◽  
pp. 11586-11599 ◽  
Author(s):  
You Peng ◽  
Chen Li ◽  
Ding-Cun Luo ◽  
Jin-Wang Ding ◽  
Wo Zhang ◽  
...  

2020 ◽  
Vol 6 (5) ◽  
pp. e273-e278
Author(s):  
Ruey Hu ◽  
George Xu ◽  
Thomas Stricker ◽  
Bingshan Li ◽  
Vivian L. Weiss ◽  
...  

Objective: Here we present 2 cases of papillary thyroid microcarcinomas (PMCs) that had metastasized at presentation. The 2015 American Thyroid Association and the American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS) criteria do not recommend biopsy of the majority of subcentimeter thyroid nodules, as PMCs are mostly indolent with excellent prognosis. However, the paradigm of active surveillance presents a conundrum on how to identify the rare patient with distant metastatic disease while avoiding unnecessary intervention in the majority. Methods: After initial discovery of incidental lesions on chest computed tomography, core or wedge biopsies of the lung lesion were performed. Thyroid nodules on ultrasound were classified by TI-RADS. Tumor DNA was sequenced, annotated, filtered on 119 known cancer genes, and filtered for variants with an exome allele frequency of <0.001. Results: A 70-year-old woman and a 29-year-old woman presented with incidental pulmonary lesions on computed tomography scan. Lung biopsy revealed lung metastases from papillary thyroid carcinoma. The thyroid nodules in both patients were TI-RADS 3 and American Thyroid Association low-suspicion. Molecular testing showed a c.1721C>G mutation (p.Thr574Ser) in the TSHR gene in patient 1 and a codon 61 mutation in the NRAS gene in patient 2. Both patients were iodine-avid, with complete structural remission in one patient and ongoing treatment with evidence of structural response in the other. Conclusion: The 2 presentations demonstrate unexpected and concerning behavior of PMCs. Both thyroid tumors were subcentimeter in diameter, meaning they would have escaped detection using traditional risk-stratification algorithms in active surveillance. Further knowledge of tumor genetics and microenvironment may assist in predicting tumor behavior in PMCs.


2017 ◽  
Vol 102 (1-2) ◽  
pp. 39-46 ◽  
Author(s):  
Woo Young Kim ◽  
Jae Bok Lee ◽  
Seung Pil Jung ◽  
Hoon Yub Kim ◽  
Sang Uk Woo ◽  
...  

The objective was to identify gene expression profile of papillary thyroid microcarcinoma. To help improve diagnosis of papillary thyroid microcarcinoma, we performed gene expression profiling and compared it to pair normal thyroid tissues. We performed microarray analysis with 6 papillary thyroid microcarcinoma and 6 pair normal thyroid tissues. Differentially expressed genes were selected using paired t test, linear models for microarray data, and significance analysis of microarrays. Real-time quantitative reverse transcription–polymerase chain reaction was used to validate the representative 10 genes (MET, TIMP1, QPCT, PROS1, LRP4, SDC4, CITED1, DPP4, LRRK2, RUNX2). We identified 91 differentially expressed genes (84 upregulated and 7 downregulated) in the gene expression profile and validated 10 genes of the profile. We identified a significant genetic difference between papillary thyroid microcarcinoma and normal tissue by 10 upregulated genes greater than 2-fold (P &lt; 0.05).


Sign in / Sign up

Export Citation Format

Share Document