Analysis of the prognostic significance and potential mechanisms of lncRNAs associated with m6A methylation in papillary thyroid carcinoma

Abstract Background : m6A methylation-related long non-coding RNAs (lncRNAs) play a significant role in the progression of various tumors and can be used as prognostic markers. However, whether m6A-related lncRNAs also play the same function as prognostic markers in papillary thyroid carcinoma (PTC) remains unclear. Methods : Consensus cluster analysis was performed to divide PTC samples obtained from The Cancer Genome Atlas database into two clusters according to the expression of m6A-related lncRNAs. Then, the least absolute shrinkage and selection operator (LASSO) regression analysis was performed to create and verify a prognostic model. Furthermore, the relationship among risk scores, clusters, programmed death-ligand 1 (PD-L1), tumor microenvironment (TME), clinicopathological characteristics, immune infiltration, immune checkpoint, and tumor mutation burden (TMB) was analyzed. In addition, a nomogram was created, and subsequently, the drug sensitivity of lncRNAs in the prognostic model was analyzed. Finally, the relationship between these lncRNAs and prognosis in pan-cancer was investigated. Results: The prognosis, RAS, BRAF, M, and TME were found to be different in two clusters. The prognostic model included three lncRNAs: PSMG3-AS1 , BHLHE40-AS1 , and AC016747.3 . The risk score was associated with clusters, PD-L1, tumor microenvironment, clinicopathological characteristics, immune cell infiltration, immune checkpoint, and TMB, and thus, risk score was confirmed as useful prognostic indicators. Differentially expressed lncRNAs are involved in many malignancies and can be identified as cancer prognostic makers. Conclusion : According to our research, we can regard m6A-related lncRNAs involved in the procession of PTC as a biomarker of PFS for PTC patients, and pan-cancer.

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Incidence of the CHEK2 Germline Mutation and Its Impact on Clinicopathological Features, Treatment Responses, and Disease Course in Patients with Papillary Thyroid Carcinoma

Cancers ◽

10.3390/cancers13030470 ◽

2021 ◽

Vol 13 (3) ◽

pp. 470

Author(s):

Danuta Gąsior-Perczak ◽

Artur Kowalik ◽

Krzysztof Gruszczyński ◽

Agnieszka Walczyk ◽

Monika Siołek ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Missense Mutation ◽

Vascular Invasion ◽

Germline Mutations ◽

Primary Treatment ◽

Clinicopathological Characteristics ◽

Missense Mutations ◽

Papillary Thyroid ◽

Treatment Responses

The CHEK2 gene is involved in the repair of damaged DNA. CHEK2 germline mutations impair this repair mechanism, causing genomic instability and increasing the risk of various cancers, including papillary thyroid carcinoma (PTC). Here, we asked whether CHEK2 germline mutations predict a worse clinical course for PTC. The study included 1547 unselected PTC patients (1358 women and 189 men) treated at a single center. The relationship between mutation status and clinicopathological characteristics, treatment responses, and disease outcome was assessed. CHEK2 mutations were found in 240 (15.5%) of patients. A CHEK2 I157T missense mutation was found in 12.3%, and CHEK2 truncating mutations (IVS2 + 1G > A, del5395, 1100delC) were found in 2.8%. The truncating mutations were more common in women (p = 0.038), and were associated with vascular invasion (OR, 6.91; p < 0.0001) and intermediate or high initial risk (OR, 1.92; p = 0.0481) in multivariate analysis. No significant differences in these parameters were observed in patients with the I157T missense mutation. In conclusion, the CHEK2 truncating mutations were associated with vascular invasion and with intermediate and high initial risk of recurrence/persistence. Neither the truncating nor the missense mutations were associated with worse primary treatment response and outcome of the disease.

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Histological perspective on the effects of tumor-associated macrophages in the tumor microenvironment surrounding papillary thyroid carcinoma

Polish Journal of Pathology ◽

10.5114/pjp.2016.65865 ◽

2016 ◽

Vol 4 ◽

pp. 332-344 ◽

Cited By ~ 4

Author(s):

Nuray Y. Can ◽

Semra Ayturk ◽

Mehmet Celik ◽

Yavuz A. Sezer ◽

Filiz Ozyilmaz ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Tumor Microenvironment ◽

Thyroid Carcinoma ◽

Papillary Thyroid ◽

Tumor Associated Macrophages

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Microvessel and Lymphatic Vessel Density and VEGFR-3 Expression of Papillary Thyroid Carcinoma with Comparative Analysis of Clinicopathological Characteristics

The Korean Journal of Pathology ◽

10.4132/koreanjpathol.2010.44.3.243 ◽

2010 ◽

Vol 44 (3) ◽

pp. 243 ◽

Cited By ~ 1

Author(s):

Harin Cheong ◽

Hanna Kang ◽

Hyung Kyung Kim ◽

Ji Yoon Bae ◽

Dong Eun Song ◽

...

Keyword(s):

Comparative Analysis ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Lymphatic Vessel ◽

Clinicopathological Characteristics ◽

Vessel Density ◽

Lymphatic Vessel Density ◽

Papillary Thyroid

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Association between Thyroiditis and Multifocality in Papillary Thyroid Carcinoma

International Archives of Otorhinolaryngology ◽

10.1055/s-0040-1710307 ◽

2020 ◽

Author(s):

Rogério Aparecido Dedivitis ◽

Leandro Luongo de Matos ◽

Felipe Guilherme Silva Souza ◽

Jose Luis Bogado Ortiz

Keyword(s):

Retrospective Study ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Total Thyroidectomy ◽

Direct Relationship ◽

Statistical Significance ◽

Hashimoto Thyroiditis ◽

Papillary Thyroid ◽

Multifocal Lesions ◽

The Relationship

Abstract Introduction Hashimoto thyroiditis (HT) shares many characteristics with papillary thyroid carcinoma (PTC), and some studies show that, when associated, PTC is diagnosed mostly with smaller lesions and multifocal pattern. Objective To evaluate the relationship between HT and PTC. Methods A retrospective study of 155 patients who underwent total thyroidectomy from 2009 to 2015. Demographical, clinical and ultrasonographical data, as well as anatomopathological findings were evaluated. Results There were signs of thyroidits in 35 patients, and 114 patients had a unifocal disease. There was no statistical significance between the variables studied and thyroiditis. However, when compared with the occurrence of unifocal or multifocal lesions, there was statistical significance regarding age (p = 0.038) and mass (p = 0.031). There was no direct relationship between thyroiditis and multifocality (p = 0.325) nor between thyroiditis and cervical extension of the disease (p = 0.300 e p = 0.434). Conclusion There was no relationship between thyroiditis and multifocality in cases of PTC.

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Clinicopathological Significance of Loss of p27Kip1 Expression in Papillary Thyroid Carcinoma

The International Journal of Biological Markers ◽

10.5301/jbm.5000239 ◽

2017 ◽

Vol 32 (2) ◽

pp. 255-259 ◽

Cited By ~ 4

Author(s):

Nae Yu Kim ◽

Jin Hwa Kim ◽

Jung-Soo Pyo ◽

Won Jin Cho

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Meta Analysis ◽

Thyroid Tissue ◽

Clinicopathological Characteristics ◽

Papillary Thyroid ◽

Benign Lesions ◽

Thyroid Microcarcinoma ◽

Clinicopathological Significance ◽

Expression Loss

Introduction A meta-analysis was done to investigate the clinicopathological significance of the loss of p27kip1 expression in papillary thyroid carcinoma (PTC). Methods The meta-analysis involving 17 studies included 1,652 PTC and 328 benign cases. The rate of p27kip1 expression loss in PTC and benign lesions, and the correlations between p27kip1 expression loss and clinicopathological characteristics of PTC were determined. Results The estimated rate of p27kip1 expression loss was 0.557 (95% confidence interval [CI] 0.443-0.665) and 0.139 (95% CI 0.062-0.283) in PTC and benign lesions, respectively. In subgroup analysis, the rates of p27kip1 expression loss were 0.683, 0.393, and 0.414 in the classical variant, follicular variant, and papillary thyroid microcarcinoma, respectively. Loss of p27kip1 expression was significantly correlated with lymph node metastasis and distant metastasis (odds ratio 3.559, 95% CI 1.146-11.056 and 4.735, 95% CI 1.322-16.960, respectively). Extrathyroidal extension was correlated with loss of p27kip1 expression, but not in a statistically significant way (p = 0.051). There were no significant correlations between loss of p27kip1 expression and sex, tumor size, BRAFV600E mutation, and tumor multifocality. Conclusions Loss of p27kip1 expression is frequently found in PTC compared with benign lesions and normal thyroid tissue. When present in PTC, it is correlated with aggressive tumor behavior.

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Conventional Papillary Thyroid Carcinoma With Intralobular Lymphatic Dissemination Shows More Aggressive Features

10.21203/rs.3.rs-91174/v1 ◽

2020 ◽

Author(s):

Yuanyuan Lei ◽

Wenting Huang ◽

Qiuxiao Yu ◽

Sha Feng ◽

Guihua Shen ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Vascular Tumor ◽

Biological Indicator ◽

Clinicopathological Characteristics ◽

Clinicopathological Features ◽

Braf V600e ◽

Tumor Diameter ◽

Papillary Thyroid ◽

Significant Difference

Abstract Objective: To investigate the invasive capability and other clinicopathological features of conventional papillary thyroid carcinoma (CVPTC) with intralobular lymphatic dissemination.Methods: Seventy-three CVPTC patients receiving total thyroidectomy were analyzed in this study. The expression of BRAF-V600E, D2-40 and CD31 in all thyroid samples was detected by immunohistochemical staining (IHC). The results were evaluated by two pathologists and were statistically analyzed. In addition, the rate of positive BRAF-V600E expression and the clinical invasiveness of CVPTC with intralobular dissemination (ID-CVPTC), multiple primary CVPTC (MP-CVPTC) and single focus CVPTC (SF-CVPTC) were evaluated. The correlation between BRAF-V600E expression, lymphatic vessel density (LVD), microvessel density (MVD) and the clinicopathological characteristics of CVPTC were assessed.Results: Twenty-five ID-CVPTC, 17 MP-CVPTC and 31 SF-CVPTC cases were included in this study. The positive expression rate of BRAF-V600E in ID-CVPTC (92.0%) was significantly higher than that in MP-CVPTC (70.6%) and SF-CVPTC (71.0%), while no significant difference in expression between MP-CVPTC and SF-CVPTC was detected (P > 0.05). The expression of BRAF-V600E was not related to clinicopathological features, including age, gender, lymph node metastasis (LNM), bilateral involvement, presence of vascular tumor thrombus, capsule invasion, nerve invasion or the maximum tumor diameter (P > 0.05). The LVD in the ID-CVPTC group (9.74 ± 2.98) was higher than that in the non-ID-CVPTC group (7.46 ± 2.5) (P < 0.05). Compared with cases without adenolobar dissemination, ID-CVPTC was associated with a younger age, higher LNM rate, and increased capsule and vessel invasiveness (P < 0.05).Conclusions: ID-CVPTC shows more aggressive features, and intralobular lymphatic dissemination may be a potential biological indicator of poor prognosis.

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BRAF V600E Immunoexpression in Papillary Thyroid Carcinoma and Its Association with Prognostic Factors and Histopathologic Variant

Medicinus ◽

10.19166/med.v8i1.3120 ◽

2021 ◽

Vol 8 (1) ◽

pp. 12

Author(s):

Erna Kristiani ◽

Endang SR Hardjolukito ◽

Agnes S Harahap ◽

Benyamin Makes

Keyword(s):

Prognostic Factors ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Clinicopathological Characteristics ◽

Braf V600e Mutation ◽

Braf V600e ◽

Papillary Thyroid ◽

Tall Cell Variant ◽

Tall Cell ◽

Cell Variant

Aim: to provide additional information regarding the clinicopathological characteristics of Papillary Thyroid Carcinoma (PTC). Methods: Fifty patient with PTC were reviewed to determine prognostic factors such as age, gender, size of tumor and histologic variant. BRAF V600E mutation was detected by immunohistochemical staining and assessed with H score. Result: BRAF V600E mutations were detected in 17 (34%) cases. There were seven cases with extrathyroidal extension (ETE) p 0,04, 11 cases with lymph node metastasis (LNM) p < 0,001, and 8 cases with tall cell variant p 0,047.The cases with positive BRAF V600E mutation had mean age of 44.71 years, and the size of the tumor between 0.1-4cm. Six cases of them are male and 11 female.Conclusion: There were significant relationships between BRAF V600E mutation with ETE, LNM, and tall cell variant. There was no significant relationship between BRAF V600E mutation, either with age, gender, or size of the tumor. BRAF V600E immunohistochemical examination can be performed as additional investigation for PTC patients.

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