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Genetic relationship between Hashimoto`s thyroiditis and papillary thyroid carcinoma with coexisting Hashimoto`s thyroiditis.

ABSTRACT: Hashimoto's thyroiditis (HT) is present in the background of around 30% of papillary thyroid carcinomas (PTCs). The genetic predisposition effect of this autoimmune condition is not thoroughly understood. We analyzed the microarray expression profiles of 13 HT, eight PTCs with (w/) coexisting HT, six PTCs without (w/o) coexisting HT, six micro PTCs (mPTCs), and three normal thyroid (TN) samples. Based on a false discovery rate (FDR)-adjusted p-value ? 0.05 and a fold change (FC) > 2, four comparison groups were defined, which were HT vs. TN; PTC w/ HT vs. TN; PTC w/o HT vs. TN; and mPTC vs. TN. A Venn diagram displayed 15 different intersecting and non-intersecting differentially expressed gene (DEG) sets, of which a set of 71 DEGs, shared between the two comparison groups HT vs. TN ? PTC w/ HT vs. TN, harbored the relatively largest number of genes related to immune and inflammatory functions; oxidative stress and reactive oxygen species (ROS); DNA damage and DNA repair; cell cycle; and apoptosis. The majority of the 71 DEGs were upregulated and the most upregulated DEGs included a number of immunoglobulin kappa variable genes, and other immune-related genes, e.g., CD86 molecule (CD86), interleukin 2 receptor gamma (IL2RG), and interferon, alpha-inducible protein 6 (IFI6). Upregulated genes preferentially associated with other gene ontologies (GO) were, e.g., STAT1, MMP9, TOP2A, and BRCA2. Biofunctional analysis revealed pathways related to immunogenic functions. Further data analysis focused on the set of non-intersecting 358 DEGs derived from the comparison group of HT vs. TN, and on the set of 950 DEGs from the intersection of all four comparison groups. In conclusion, this study indicates that, besides immune/inflammation-related genes, also genes associated with oxidative stress, ROS, DNA damage, DNA repair, cell cycle, and apoptosis are comparably more deregulated in a data set shared between HT and PTC w/ HT. These findings are compatible with the conception of a genetic sequence where chronic inflammatory response is accompanied by deregulation of genes and biofunctions associated with oncogenic transformation. The generated data set may serve as a source for identifying candidate genes and biomarkers that are practical for clinical application.

SUBMITTER: Subhi O

PROVIDER: S-EPMC7326236 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Genetic relationship between Hashimoto`s thyroiditis and papillary thyroid carcinoma with coexisting Hashimoto`s thyroiditis.

Subhi Ohoud O Schulten Hans-Juergen HJ Bagatian Nadia N Al-Dayini Roa'a R Karim Sajjad S Bakhashab Sherin S Alotibi Reem R Al-Ahmadi Alaa A Ata Manar M Elaimi Aisha A Al-Muhayawi Saad S Mansouri Majid M Al-Ghamdi Khalid K Hamour Osman Abdel OA Jamal Awatif A Al-Maghrabi Jaudah J Al-Qahtani Mohammed Hussain MH

PloS one 20200630 6

Hashimoto's thyroiditis (HT) is present in the background of around 30% of papillary thyroid carcinomas (PTCs). The genetic predisposition effect of this autoimmune condition is not thoroughly understood. We analyzed the microarray expression profiles of 13 HT, eight PTCs with (w/) coexisting HT, six PTCs without (w/o) coexisting HT, six micro PTCs (mPTCs), and three normal thyroid (TN) samples. Based on a false discovery rate (FDR)-adjusted p-value ≤ 0.05 and a fold change (FC) > 2, four compar ...[more]

PMID: 32603365

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Project description:The aim of the present study was to evaluate the association between coexisting lymphocytic thyroiditis (LT) and the clinicopathological features of papillary thyroid carcinoma (PTC). The records of 458 patients with PTC who underwent a total thyroidectomy and lymph node dissection in Sir Run Run Shaw Hospital (Hangzhou, China) were analyzed. In accordance with the histopathology of thyroid parenchyma, the cases were divided into three groups, including Hashimoto's thyroiditis (HT), non-Hashimoto's type LT (NHLT) and no LT. Based on the histopathology, data on age, sex, maximum diameter of tumor, multifocality, extrathyroidal extension, metastatic lymph node size, extranodal extension and tumor grades in the different groups were analyzed and compared. The prevalence of coexisting LT was 29.0% (133/458), of which 7.6% (35/458) was HT and 21.4% (98/458) was NHLT. PTC concomitant with LT was significantly associated with female patients (95.5 vs. 70.2%; P<0.001), a lower rate of extrathyroidal extension and/or capsular invasion (25.6 vs. 39.7%; P=0.004), central lymph node metastasis (CLNM) ratio (10.71 vs. 17.37; P=0.014), higher number of dissected central lymph nodes (16.83 vs. 11.7; P<0.001), larger metastatic lymph nodes (0.66 vs. 0.46 cm; P<0.001), higher occurrence of multifocality (61.7 vs. 50.5%; P=0.029) and earlier pT stage (57.9 vs. 38.8%; P<0.001), regardless of the combined or separate consideration of HT and NHLT. Besides, LT was associated with multifocality [odds ratio (OR), 1.578; 95% confidence interval (CI), 1.046-2.382; P=0.030]. Furthermore, in patients with PTC, CLNM had a significant association with the male sex (OR, 2.000; 95% CI, 1.216-3.288; P=0.006), an age of <45 years (OR, 0.592; 95% CI, 0.398-0.879; P=0.009) and a tumor size of >1 cm (OR, 3.913; 95% CI, 2.431-5.734; P<0.001). In conclusion, patients with PTC and LT showed a greater female preponderance, multifocality, a lower extrathyroidal extension and a lower CLNM ratio. LT was associated with an increased risk of multifocality in PTC.

Project description:ImportanceHashimoto thyroiditis (HT) has been suggested to be associated with papillary thyroid cancer (PTC) development. However, its association with PTC progression remains unclear.ObjectiveTo examine the association between HT and PTC presentation and outcomes.Design, setting, and participantsThis retrospective cohort study included a review of patients aged 18 to 75 years who had pathologically confirmed PTC treated at a single center in China from January 1, 2001, to December 31, 2014. Data analysis was performed from November 1 to December 31, 2020.ExposuresCoexistent HT was defined according to evaluation of postoperative paraffin sections.Main outcomes and measuresThe primary outcome was the association of HT with PTC-related mortality, assessed using Cox proportional hazards regression models. The secondary outcome was the association of HT with aggressive characteristics and structural recurrence of PTC, assessed using logistic regression and Cox proportional hazards regression with and without adjustment for related factors.ResultsOf 9210 patients with PTC (mean [SD] age, 43.6 [12.0] years; 6872 [75%] women) included in the analysis, 1751 (19%) had HT. In the logistic regression model, HT was negatively associated with frequencies of primary tumor size of 4 cm or greater (adjusted odds ratio [aOR], 0.20; 95% CI, 0.12-0.33; P < .001), gross extrathyroidal extension (aOR, 0.44; 95% CI, 0.36-0.54; P < .001), extranodal extension (aOR, 0.66; 95% CI, 0.55-0.80; P < .001), and distant metastasis (aOR, 0.17; 95% CI, 0.04-0.71; P = .02). After a median follow-up of 85 months (range, 12-144 months), 131 PTC-related deaths were identified in the cohort; 2 patients who died had HT. Patients with HT had significantly superior outcomes compared with patients without HT in terms of unadjusted 10-year disease-specific survival (99.9% vs 96.6%; log-rank P < .001) and recurrence-free survival (92.0% vs 87.6%; log-rank P = .001). After adjusting for sex, age, primary tumor size, extrathyroidal extension, lymph node metastasis, distant metastasis, extent of surgery, and radioactive iodine ablation, HT was associated with decreased PTC-related mortality (hazard ratio [HR], 0.19; 95% CI, 0.05-0.76; P = .02). Stratified analysis showed that HT was associated with less frequent structural recurrence in patients with extrathyroidal extension (HR, 0.52; 95% CI, 0.38-0.71; P < .001; P = .002 for interaction) or after total thyroidectomy (HR, 0.50; 95% CI, 0.35-0.69; P < .001; P = .009 for interaction).Conclusions and relevanceIn this cohort study, patients with coexistent HT had less aggressive characteristics at presentation and better outcomes of PTC than did patients without HT. The findings suggest that autoimmune thyroiditis has a protective role in association with thyroid cancer.

Project description:Background Parathyroid adenoma (PA) is a common but relatively poorly understood endocrine tumor. A significant number of PA patients also have papillary thyroid carcinoma (PTC). The clinicopathological characteristics of PA and its relationship with PTC need further study. Methods The clinical data of 99 PA patients were reviewed and the clinicopathologic features of PA were analyzed. PTC occurred in 22 PA patients. The clinicopathologic features of 22 patients with PA + PTC and 77 patients with PA alone were compared. According to age, gender and thyroid surgery methods, 22 PA + PTC patients were matched with 1,123 patients with PTC alone during the same period. The pathological characteristics of the two groups of patients were compared. All data analysis was performed using SPSS23.0, variables were compared by t-test, chi square test or Mann Whitney U-test as appropriate. Results Ninety-nine PA patients (21 males, 78 females) with a median age of 51 [10–80] years were included. The preoperative parathyroid hormone (PTH) (P=0.007) and preoperative blood calcium (P=0.036) of male patients were higher than those of female patients, and the proportion of asymptomatic patients (P=0.008) and postoperative PTH level (P=0.013) were lower. The preoperative PTH level (P=0.002), preoperative blood calcium level (P=0.004), preoperative alkaline phosphatase (ALP) level (P=0.018) and postoperative PTH levels (P=0.023) in PA + PTC group were lower than those in PA group. The asymptomatic rate was higher in PTC + PA group than that in PA group (P<0.001). There was no statistical difference between PA + PTC group and PTC group in multifocal tumor, capsule invasion, lymph node metastasis (P>0.05). The lymph node metastasis rate in PA + PTC group (9/215) was significantly lower than that in PTC group (37/337) (P=0.005). Conclusions PA exhibited the following characteristics: occurred in all age groups; more common in women but more severe in men; more located in the lower pole. The coexistence of PTC and PA did not promote the progression of PA, nor did it increase the aggressiveness of PTC. Conversely, their co-existence may lead to early diagnosis of the disease. PA patients (22.2%) also have PTC, so surgeons should pay attention to thyroid disease to prevent the need for reoperation.

Dataset Information

Genetic relationship between Hashimoto`s thyroiditis and papillary thyroid carcinoma with coexisting Hashimoto`s thyroiditis.

Publications

Genetic relationship between Hashimoto`s thyroiditis and papillary thyroid carcinoma with coexisting Hashimoto`s thyroiditis.

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