Dataset Information

Impact of Epithelial-Mesenchymal Immunophenotype on Local Aggressiveness in Papillary Thyroid Carcinoma Invading the Airway.

ABSTRACT: Primary thyroid tumours show different levels of aggressiveness, from indolent to rapidly growing infiltrating malignancies. The most effective therapeutic option is surgery when radical resection is feasible. Biomarkers of aggressiveness may help in scheduling extended resections such as airway infiltration, avoiding a non-radical approach. The aim of the study is to evaluate the prognostic role of E-cadherin, N-cadherin, Aryl hydrocarbon receptor (AhR), and CD147 in different biological behaviours. Fifty-five samples from three groups of thyroid carcinomas were stained: papillary thyroid carcinomas (PTCs) infiltrating the airway (PTC-A), papillary intra-thyroid carcinomas (PTC-B) and poorly differentiated or anaplastic thyroid carcinomas (PDTC/ATC). High expressions of N-cadherin and AhR were associated with higher locoregional tumour aggressiveness (p = 0.005 and p < 0.001 respectively); PDTC/ATC more frequently showed a high expression of CD147 (p = 0.011), and a trend of lower expression of E-cadherin was registered in more aggressive neoplasms. Moreover, high levels of AhR were found with recurrent/persistent diseases (p = 0.031), particularly when tumours showed a concomitant high N-cadherin expression (p = 0.043). The study suggests that knowing in advance onco-biological factors with a potential role to discriminate between different subsets of patients could help the decision-making process, providing a more solid therapeutic indication and an increased expectation for radical surgery.

SUBMITTER: Mandarano M

PROVIDER: S-EPMC8509765 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Impact of Epithelial-Mesenchymal Immunophenotype on Local Aggressiveness in Papillary Thyroid Carcinoma Invading the Airway.

Mandarano Martina M Andolfi Marco M Colella Renato R Monacelli Massimo M Polistena Andrea A Moretti Sonia S Bellezza Guido G Puxeddu Efisio E Sanguinetti Alessandro A Sidoni Angelo A Avenia Nicola N Puma Francesco F Vannucci Jacopo J

Journal of clinical medicine 20210924 19

Primary thyroid tumours show different levels of aggressiveness, from indolent to rapidly growing infiltrating malignancies. The most effective therapeutic option is surgery when radical resection is feasible. Biomarkers of aggressiveness may help in scheduling extended resections such as airway infiltration, avoiding a non-radical approach. The aim of the study is to evaluate the prognostic role of E-cadherin, N-cadherin, Aryl hydrocarbon receptor (AhR), and CD147 in different biological behavi ...[more]

PMID: 34640369

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Project description:Papillary thyroid carcinoma (PTC) is the fastest-growing disease caused by numerous molecular alterations in addition to previously reported DNA mutations. There is a compelling need to identify novel transcriptomic alterations that are associated with the pathogenesis of PTC with potential diagnostic and prognostic implications. Methods: We gathered and compared 242 expression profiles between paired PTC and adjacent normal tissues and identified and validated the coding and long non-coding RNAs (lncRNAs) associated with the extrathyroidal extension (ETE) of 655 PTC patients in two independent cohorts, followed by predicting their interactions with drugs. Co-expression, RNA interaction, Kaplan-Meier survival and multivariate Cox proportional regression analyses were performed to identify dysregulated lncRNAs and genes that correlated with clinical outcomes of PTC. Alternative splicing (AS), RNA circularization, and editing were also compared between transcriptomes to expand the repertoire of molecular alterations in PTC. Results: Numerous genes related to cellular microenvironment and steroid hormone response were associated with the ETE of PTC. Drug susceptibility predictions of the expression signature revealed two highly ranked compounds, 6-bromoindirubin-3'-oxime and lovastatin. Co-expression and RNA interaction analysis revealed the essential role of lncRNAs in PTC pathogenesis by modulating extracellular matrix and cell adhesion. Eight genes and two novel lncRNAs were identified that correlated with the aggressive nature and disease-free survival of PTC. Furthermore, this study provided the transcriptome-wide landscape of circRNAs in PTC and uncovered dissimilar expression profiles among circRNAs originating from the same host gene, suggesting the functional complexity of circRNAs in PTC carcinogenesis. The newly identified AS events in the SERPINA1 and FN1 genes may improve the sensitivity and specificity of these diagnostic biomarkers. Conclusions: Our study uncovered a comprehensive transcriptomic signature associated with the carcinogenesis and aggressive behavior of PTC, as well as presents a catalog of 10 potential biomarkers, which would facilitate PTC prognosis and development of new therapeutic strategies for this cancer.

Project description:Background: Papillary thyroid carcinoma (PTC) is one of the most common endocrine malignant tumors. Poor prognoses such as high recurrence rate always appear in PTC patients with cervical lymph node metastasis. The process of ubiquitination plays important roles in PTC. As ubiquitin E3 ligases, Deltex (DTX) family proteins were reported to associate with multiple cancers. However, functions and mechanisms of DTX3 in PTC are currently unknown. Methods: In this study, DTX3 expressions were examined in 114 PTC and paired paracancerous normal tissues through quantitative real-time polymerase chain reaction and western blot. The clinical significances of DTX3 expressions in PTC patients were also investigated. After stable transfection with either short hairpin RNA to knock down DTX3 expression or full-length complementary DNA to upregulate DTX3 expression, changes of malignant phenotypes in two PTC cell lines K1 and TPC-1 were observed using cell viability, flow cytometry, wound healing and transwell assays. Afterwards, altered expressions of epithelial-mesenchymal transition (EMT) and AKT signal pathway related proteins were measured by western blot. Immunoprecipitation and mass spectrometry (IP-MS), immunofluorescence and Co-IP were utilized to identify the possible DTX3 interacting proteins. Results: Both mRNA and protein expressions of DTX3 were lower in PTC tissues and correlated with the presence of cervical lymph node metastasis (P<0.05). DTX3 overexpression inhibited migration and invasion of PTC cells, decreased Vimentin and phosphorylated AKT expressions, but promoted E-cadherin expression (P<0.05). Moreover, knockdown of DTX3 led to opposite changes (P<0.05). Total 46 probable DTX3 interacting proteins were identified by IP-MS. Among them, X-ray repair cross-complementing protein 5 (XRCC5) and NADH: Ubiquinone Oxidoreductase Complex Assembly Factor 5 (NDUFAF5) were verified to be associated with DTX3. Moreover, DTX3 was proved to be co-localized with XRCC5 in nucleus and promote ubiquitination of XRCC5. Conclusions: DTX3 suppresses EMT by partially facilitating ubiquitination of XRCC5 to inhibit AKT signal pathway in PTC.

Dataset Information

Impact of Epithelial-Mesenchymal Immunophenotype on Local Aggressiveness in Papillary Thyroid Carcinoma Invading the Airway.

Publications

Impact of Epithelial-Mesenchymal Immunophenotype on Local Aggressiveness in Papillary Thyroid Carcinoma Invading the Airway.

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