Molecular Alterations in Relation to Histopathological Characteristics in a Large Series of Pediatric Papillary Thyroid Carcinoma from a Single Institution

Macerola, Elisabetta; Proietti, Agnese; Poma, Anello Marcello; Ugolini, Clara; Torregrossa, Liborio; Vignali, Paola; Basolo, Alessio; Materazzi, Gabriele; Elisei, Rossella; Santini, Ferruccio; Basolo, Fulvio

doi:10.3390/cancers13133123

Cited by 20 publications

(18 citation statements)

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“…It has been reported that CPTCs were less represented in patients aged less than 15 years than in patients aged 15-18 years, while FVPTCs occurred more frequently in the former group ( 20 ). However, our results showed that the proportion of CPTCs was higher than that of FVPTCs, both in children aged ≤18 years and in young children aged 2-16 years regardless of with or without DM.…”

Section: Discussionmentioning

confidence: 97%

“…Within the pediatric group under 18 years of age, special attention should be paid to male patients under 15 years old, as they are associated with a more advanced disease at diagnosis ( 5 ). Tumors were generally infiltrative in patients younger than 15 years ( 20 ). Therefore, we believe that it is necessary to take the age into consideration to divide young children separately from adolescents during the development and disease progression of PTC.…”

Section: Discussionmentioning

confidence: 99%

“…CPTC was a strong predictor of high recurrence risk and high cancer-specific mortality, with a worse prognosis than FVPTC ( 9 ). In a study including 163 patients aged less than 18 years diagnosed as PTC, BRAF mutations and RET and NTRK fusions were detected mainly in CPTCs ( 20 ). The presence of a BRAFV600E mutation was reported to be correlated significantly with the need for a second treatment during the follow-up in patients under 18 years of age, and BRAF mutations might be associated with more aggressive clinical features and a higher risk of recurrence or persistence of disease in the pediatric population ( 5 ).…”

Section: Discussionmentioning

confidence: 99%

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High Incidence of Distant Metastasis Is Associated With Histopathological Subtype of Pediatric Papillary Thyroid Cancer - a Retrospective Analysis Based on SEER

et al. 2021

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ObjectiveChildren with papillary thyroid cancer (PTC) have a higher invasive rate and distant metastasis rate, but the mortality rate is lower with unknown reasons. The majority of PTC cases comprise classical papillary thyroid carcinoma (CPTC) and follicular variant papillary thyroid carcinoma (FVPTC). This study aimed to determine the relationship between histopathological subtype and rate of distant metastasis and investigate factors influencing distant metastasis in pediatric PTC.MethodsA total of 102,981 PTC patients were recruited from SEER registry, 2004-2015. Proportion of distant metastasis between children (≤18 years) and adults with different histopathological subtypes was compared by propensity score matching. The cut-off age for distant metastasis in children was calculated by receiver operating characteristic (ROC) curve, and the risk factors for distant metastasis in pediatric patients were analyzed by logistic regression models.ResultsAmong the 1,484 children and 101,497 adults included in the study, the incidence of CPTC patients with distant metastasis in children was higher than that in adults (p<0.001). The ROC curve was calculated, which yielded a cut-off age for distant metastasis in CPTC children as 16 years old. In CPTC, the proportion of young children (2-16 years) with distant metastasis was higher than that of adolescents (17-18 years) and adults (>18 years) (both p<0.001). While there was no such trend in FVPTC. In young children (2-16 years), the incidence of CPTC with distant metastasis was higher than FVPTC (p=0.006). There was no difference between the proportion of CPTC and FVPTC with distant metastasis in adolescents (17-18 years) and adults. Logistic regression models revealed that extrathyroidal extension, lymph node metastasis and CPTC histopathological subtype were risk factors for distant metastasis in young children aged 2 -16 years.ConclusionsIn CPTC, the incidence of distant metastasis in young children (2-16 years) was significantly higher than that in adolescents (17-18 years) and adults (>18 years). In patients with distant metastasis aged 2-16 years, the proportion of CPTC was higer than that of FVPTC. Extrathyroidal extension, lymph node metastasis, and CPTC histopathological subtype were risk factors for distant metastasis in young children aged 2-16 years.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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High Incidence of Distant Metastasis Is Associated With Histopathological Subtype of Pediatric Papillary Thyroid Cancer - a Retrospective Analysis Based on SEER

et al. 2021

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“…In a previous study, gene mutations were found to play important roles in thyroid cancer progression and development [ 27 ]. Additional file 1 : Fig.…”

Section: Resultsmentioning

confidence: 99%

BRAF-activated WT1 contributes to cancer growth and regulates autophagy and apoptosis in papillary thyroid carcinoma

Chen

Lin

Lin³

et al. 2022

J Transl Med

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Background Papillary thyroid carcinoma (PTC) is one of most prevalent malignant endocrine neoplasms, and it is associated with a high frequency of BRAF gene mutations, which lead to lymphatic metastasis and distant metastasis that promote tumor progression. The molecular mechanism of PTC and the role of BRAF mutation in PTC progression and development need to be further elucidated. Methods In this study, a comprehensive bioinformatics analysis was performed to identify the differentially expressed genes and signaling pathways in thyroid cancer patients carrying mutant BRAF. Then, we confirmed the prognostic role of WT1 in thyroid cancer patients. Immunohistochemistry was performed to measure the expression profile of WT1 in PTC tissue. Lentivirus shWT1 was transfected into BRAFV600E (mutant) PTC cells to stably inhibit WT1 expression. CCK-8, EdU, immunofluorescence, colony formation, cell migration, cell wound healing, apoptosis and autophagy assays were performed to assess the biological functions of WT1 in BRAFV600E PTC cells. RNA sequencing, immunohistochemistry and immunoblotting were performed to explore the molecular mechanism of WT1 in BRAFV600E PTC cells. Results The results confirmed that “epithelial cell proliferation”, “apoptosis” and “selective autophagy” were closely associated with this BRAF mutant in these thyroid cancer patients. Knocking down BRAF-activated WT1 effectively inhibited the proliferation and migration of BRAFV600E PTC cells. Silencing WT1 significantly inhibited autophagy and promoted the apoptosis of BRAFV600E PTC cells. Mechanistic investigations showed that silencing WT1 expression remarkably suppressed the AKT/mTOR and ERK/P65 signaling pathways in BRAFV600E PTC cells. Conclusion All these results indicate that WT1 is a promising prognostic biomarker and facilitates PTC progression and development of cells carrying the BRAFV600E mutation.

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“…We discuss the THADA gene (also called thyroid adenoma-associated protein) separately, located on the short arm 2p21 of chromosome 2, first discovered in thyroid tumors ( Rippe et al, 2003 ). THADA encodes a thyroid adenoma-related protein in the thyroid, pancreas, and other tissues ( Ling, 2020 ; Castillo-Higuera et al, 2021 ; Macerola et al, 2021 ), which is related to energy metabolism disorders. In this study, we found that the missense and amplification of this gene in the IS3 subtype were significantly lower than the other two subtypes, and its expression was consistent with a better prognostic trend.…”

Section: Discussionmentioning

confidence: 99%

Immune Classification and Immune Landscape Analysis of Triple-Negative Breast Cancer

Jiao

et al. 2021

Front. Genet.

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Background: To classify triple-negative breast cancer (TNBC) immunotyping using the public database, analyze the differences between subtypes in terms of clinical characteristics and explore the role and clinical significance of immune subtypes in TNBC immunotherapy.Methods: We downloaded TNBC data from the cBioPortal and GEO databases. The immune genes were grouped to obtain immune gene modules and annotate their biological functions. Log-rank tests and Cox regression were used to evaluate the prognosis of immune subtypes (IS). Drug sensitivity analysis was also performed for the differences among immune subtypes in immunotherapy and chemotherapy. In addition, dimension reduction analysis based on graph learning was utilized to reveal the internal structure of the immune system and visualize the distribution of patients.Results: Significant differences in prognosis were observed between subtypes (IS1, IS2, and IS3), with the best in IS3 and the worst in IS1. The sensitivity of IS3 to immunotherapy and chemotherapy was better than the other two subtypes. In addition, Immune landscape analysis found the intra-class heterogeneity of immune subtypes and further classified IS3 subtypes (IS3A and IS3B). Immune-related genes were divided into seven functional modules (The turquoise module has the worst prognosis). Five hub genes (RASSF5, CD8A, ICOS, IRF8, and CD247) were screened out as the final characteristic genes related to poor prognosis by low expression.Conclusions: The immune subtypes of TNBC were significantly different in prognosis, gene mutation, immune infiltration, drug sensitivity, and heterogeneity. We validated the independent role of immune subtypes in tumor progression and immunotherapy for TNBC. This study provides a new perspective for personalized immunotherapy and the prognosis evaluation of TNBC patients in the future.

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Molecular Alterations in Relation to Histopathological Characteristics in a Large Series of Pediatric Papillary Thyroid Carcinoma from a Single Institution

Abstract: Papillary thyroid carcinoma (PTC) presents distinct clinico-pathological and molecular differences in children compared with adult patients. Whether the presence of rearrangements or point mutations is associated with aggressive PTC clinical presentation is still controversial.

Cited by 20 publications

References 25 publications

High Incidence of Distant Metastasis Is Associated With Histopathological Subtype of Pediatric Papillary Thyroid Cancer - a Retrospective Analysis Based on SEER

High Incidence of Distant Metastasis Is Associated With Histopathological Subtype of Pediatric Papillary Thyroid Cancer - a Retrospective Analysis Based on SEER

BRAF-activated WT1 contributes to cancer growth and regulates autophagy and apoptosis in papillary thyroid carcinoma

Immune Classification and Immune Landscape Analysis of Triple-Negative Breast Cancer

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