Transcriptome analysis of papillary thyroid cancer harboring telomerase reverse transcriptase promoter mutation

Chien, Ming Nan; Yang, Po Sheng; Hsu, Yi Chiung; Liu, Tsang Pai; Lee, Jie Jen; Cheng, Shih‐Ping

doi:10.1002/hed.25385

Cited by 18 publications

(17 citation statements)

References 53 publications

(109 reference statements)

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“…So far, there was only one published study that analyzed the impact of the presence of TERT p mutations on PTC transcriptome [ 18 ]. Chien et al, who used the data obtained from the TCGA study [ 4 ], found TERT p mutations to be associated with proliferative and metabolic alterations in PTC.…”

Section: Discussionmentioning

confidence: 99%

“…However, the data concerning their molecular consequences and potential differences/similarities to BRAF V600E-positive TCs are scarce. To our best knowledge, there was only one published study devoted to the transcriptomic analysis of TERT p-mutated PTCs [ 18 ]. Therefore, in the present study, we focused on the gene expression profile of TERT p-mutated PTC in BRAF(+) cases.…”

Section: Introductionmentioning

confidence: 99%

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TERT Promoter Mutations and Their Impact on Gene Expression Profile in Papillary Thyroid Carcinoma

Rusinek

Pfeifer

Cieślicka

et al. 2020

Cancers

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TERT Promoter Mutations and Their Impact on Gene Expression Profile in Papillary Thyroid Carcinoma

Rusinek

Pfeifer

Cieślicka

et al. 2020

Cancers

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“…A propensity score matching was calculated to take into account selection biases as well as confounding factors between the two groups as previously described. 13 After an initial comparison of papillary thyroid carcinomas and microcarcinomas, patients were matched in a 2:1 analysis with the nearest neighbor matching method. The 2:1 control-case ratio was chosen to improve precision and maintain statistical power without an increase in bias.…”

Section: Propensity Score Matchingmentioning

confidence: 99%

Is papillary thyroid microcarcinoma a biologically different disease? A propensity score‐matched analysis

Hsu

Lee

Chien

et al. 2019

Journal of Surgical Oncology

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Background Papillary thyroid microcarcinoma exhibits an indolent clinical course and could be a candidate for active surveillance in the appropriate setting. It remains unknown whether papillary microcarcinoma is biologically different from larger papillary carcinoma >1 cm. Methods We analyzed clinicopathological information and transcriptome data of papillary thyroid cancer samples from The Cancer Genome Atlas. Propensity‐score matching was used to construct a matched cohort consisting of 29 microcarcinomas and 58 carcinomas. Principal component analysis and unsupervised hierarchical cluster analysis were carried out to investigate the similarity of gene expression profiles. Results After adjustment for differences in baseline clinicopathological and genetic factors, transcriptome could be grouped mainly on the basis of tumor class (BRAF‐like vs RAS‐like) and tumor size (microcarcinoma vs carcinoma). The gene set enrichment analysis showed that extracellular matrix‐associated pathways were enriched in the MSigDB database. Conclusion Papillary thyroid microcarcinomas display a distinct gene expression pattern different from the corresponding carcinomas. We hypothesize that tumor microenvironment may play a role in the microcarcinoma/carcinoma phenotypic divergence.

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“…IDH1 mutation upregulates p21 expression via sterol regulatory element-binding protein 1, inhibits phosphorylation of Rb and promotes the progression of the cell cycle from G 1 to S phase (45). The involvement of telomerase in regulating the cell cycle is primarily dependent on the progression of S phase (46). TERT promoter mutation can increase the telomerase reverse transcriptase expression and telomerase activity (47).…”

Section: Skp2 Expression --------------------------------------------mentioning

confidence: 99%

High S phase kinase‑associated protein 2 expression is a potential prognostic biomarker for glioma

et al. 2020

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S phase kinase-associated protein 2 (SKP2), a substrate recognizing protein, serves an important role in promoting cell cycle progression through ubiquitination and degradation of cell cycle inhibitors. In the present study, the clinical significance of SKP2 in gliomas was studied; 395 glioma specimens and 20 non-neoplastic tissues were collected and immunohistochemical analysis was performed. χ 2 test was used to assess the associations between SKP2 expression and clinical parameters. Overall survival (OS) curves were plotted according to the Kaplan-Meier method. In the tested glioma samples, SKP2 expression was mainly observed in glioblastomas (GBMs). Survival analysis demonstrated that the overall survival time of the high SKP2 expression group was lower compared with the low SKP2 expression group (median OS, 10.04 months vs. 16.50 months; P= 0.003). Moreover, SKP2 was independently associated with an unfavorable prognosis in GBMs. In addition, the expression of SKP2 was associated with the expression of phosphorylated retinoblastoma protein and the epidermal growth factor receptor. A combination of SKP2 expression along with isocitrate dehydrogenase 1 (IDH1) mutations and telomerase reverse transcriptase (TERT) promoter mutations was used to classify glioma patients for survival analysis. Patients with low SKP2 expression, IDH1 mutation and wild-type TERT promoter demonstrated the longest survival time. The findings of the present study, indicate that SKP2 is a potential prognostic biomarker in patients with GBMs.

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Transcriptome analysis of papillary thyroid cancer harboring telomerase reverse transcriptase promoter mutation

Abstract: The TERT promoter mutations were associated with proliferative and metabolic alterations in PTC.

Cited by 18 publications

References 53 publications

TERT Promoter Mutations and Their Impact on Gene Expression Profile in Papillary Thyroid Carcinoma

TERT Promoter Mutations and Their Impact on Gene Expression Profile in Papillary Thyroid Carcinoma

Is papillary thyroid microcarcinoma a biologically different disease? A propensity score‐matched analysis

High S phase kinase‑associated protein 2 expression is a potential prognostic biomarker for glioma

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