Background: Lymph node metastasis (LNM) occurs frequently in young papillary thyroid carcinoma (PTC) patients, though the mortality rates are low. We aimed to analyze the relationship between age at diagnosis and LNM in PTC at a population level to elucidate the clinical behavior of PTC. Methods: Data of adult patients with surgically treated PTC and follicular thyroid carcinoma (FTC) were identified from the Surveillance, Epidemiology, and End Results (SEER) database (2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015) to investigate the relationship between age and clinical characteristics by curve estimation. The adjusted odds ratio of age and LNM rate were determined.Results: A total of 50,347 PTC (48,166) and FTC (2181) (median age: 45 and 50 years, respectively) patients met the inclusion criteria; 44.5% of those with PTC (21,428) had LNM. Rank-sum test analysis indicated differences in distribution of age in LNM-positive and LNM-negative PTC. The relationship between age, tumor size and LNM showed a quadratic curve in PTC. The mean tumor diameter and LNM rate correlated linearly with age in 18-59year-old patients. LNM rate decreased with age (R 2 = 0.932, P < .0001), especially women (R 2 = 0.951, P < .0001). Conclusion:In young and middle-aged PTC patients, LNM may resolve spontaneously with delayed diagnosis and management. Active surveillance of low-risk PTC is justified.
Longer BCG maintenance therapy (such as 3 years) is not superior to shorter maintenance therapy (such as 1 year). But maintenance therapy overall is better than induction-only BCG therapy while not increasing side effects. Though further evidence and clinical practice with balanced confounding factors (risk stratification and BCG strain) are wished for, the current study suggests the common use of 1 year intravesical BCG instillation for NMIBC patients.
Background. Medullary thyroid carcinoma (MTC) accounts for 1%–2% of thyroid cancer in the United States based on the latest Surveillance, Epidemiology, and End Results (SEER) data, and this study aimed to construct a comprehensive predictive nomogram based on various clinical variables in MTC patients who underwent total thyroidectomy and neck lymph nodes dissection. Methods. Data regarding 1,237 MTC patients who underwent total thyroidectomy and neck lymph nodes dissection from 2004 to 2015 were obtained from the SEER database. Univariate and multivariate Cox regression analyses were used to screen for meaningful independent predictors. These independent factors were used to construct a nomogram model, a survival prognostication tool for 3- and 5-year overall survival, and cancer-specific survival among these MTC patients. Result. A total of 1,237 patients enrolled from the SEER database were randomly divided into the training group (n = 867) and the test group (n = 370). Univariate and multivariate Cox regression analyses were used to identify meaningful independent prognostic factors ( P < 0.05 ). Tumor size, age, metastasis status, and LNR were selected as independent predictors of overall survival (OS) and cancer-specific survival (CSS). Finally, two nomograms were developed, and the predicted C-index of overall survival (OS) and cancer-specific survival (CSS) rate in the training group was 0.828 and 0.904, respectively. The predicted C-index of overall survival (OS) and cancer-specific survival (CSS) rate in the test group was 0.813 and 0.828. Conclusion. Nomograms constructed by using various clinical variables can make more comprehensive and accurate predictions for MTC patients who underwent total thyroidectomy and neck lymph nodes. These predictive nomograms help identify postoperative high-risk MTC patients and facilitate patient counseling on clinical prognosis and follow-up.
ObjectiveThe objective of this research was to screen prognostic related genes of thyroid papillary carcinoma (PTC) by single-cell RNA sequencing (scRNA-seq), to construct the diagnostic and prognostic models based on The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA) data, and to evaluate the association between tumor immune microenvironment and the prognostic model.MethodThe differentially expressed genes (DEGs) and tumor evolution were analyzed by scRNA-seq based on public databases. The potential regulatory networks of DEGs related to prognosis were analyzed by multi-omics data in the THCA. Logistic regression and Cox proportional hazards regression were utilized to construct the diagnosis and prognostic model of PTC. The performance of the diagnostic model was verified by bulk RNA sequencing (RNA-seq) of our cohort. The tumor immune microenvironment associated with the prognostic model was evaluated using multi-omics data. In addition, qRT-PCR was performed on tumor tissues and adjacent normal tissues of 20 patients to verify the expression levels of DEGs.ResultsThe DEGs screened by scRNA-seq can distinguish between tumor and healthy samples. DEGs play different roles in the evolution from normal epithelial cells to malignant cells. Three DEGs ((FN1, CLU, and ANXA1)) related to prognosis were filtered, which may be regulated by DNA methylation, RNA methylation (m6A) and upstream transcription factors. The area under curve (AUC) of the diagnostic model based on 3-gene in the validation of our RNA-seq was 1. In the prognostic model based on 3-gene, the overall survival (OS) of high-risk patients was shorter. Combined with the clinical information of patients, a nomogram was constructed by using tumor size (pT) and risk score to quantify the prognostic risk. The age and tumor size of high-risk patients in the prognostic model were greater. In addition, the increase of tumor mutation burden (TMB) and diversity of T cell receptor (TCR), and the decrease of CD8+ T cells in high-risk group suggest the existence of immunosuppressive microenvironment.ConclusionWe applied the scRNA-seq pipeline to focus on epithelial cells in PTC, simulated the process of tumor evolution, and revealed a prognostic prediction model based on 3 genes, which is related to tumor immune microenvironment.
Background: Multiple studies showed that long-chain noncoding RNA H19 (LncRNA H19) is high-expressed in human and mouse abdominal aortic aneurysms (AAAs). We speculated that it plays an important role in arterial disease, and therefore studied the role and mechanism of H19 in aortic dissection (AD). Methods: The expressions of related genes in human aortic smooth muscle cells (HASMCs) induced by platelet-derived growth factor BB (PDGF-BB) or in the aortic tissue of AD patients/mice were identified by Western blot and quantitative real-time polymerase chain reaction. The targeting relationship between H19 and miR-193b-3p was predicted and verified by bioinformatics analysis, dual luciferase assay, RNA pull-down assay, RNA immunoprecipitation (RIP), and Pearson correlation coefficient. The H19 and miR-193b-3p effects on the biological functions of tissues and cells were examined by MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, thiazolyl blue tetrazolium bromide) assay, wound-healing assay, and Hematoxylin–Eosin (HE) staining. Results: LncRNA H19 was abnormally high-expressed in thoracic aorta tissues of AD patients, and it could competitively bind to and inhibit miR-193b-3p. In the PDGF-BB group, the expressions of H19, matrix metallopeptidase (MMP) 2 (MMP-2) and MMP-9 were up-regulated and the expressions of miR-193b-3p, α-SMA, and SM22α were down-regulated; moreover, the proliferation and migration rate of HASMCs were increased. However, H19 silencing reversed the regulation of PDGF-BB on HASMCs. More interestingly, miR-193b-3p inhibitor could partially reverse the effect of H19 silencing. In addition, the above results were verified by animal experiments, showing that shH19 and up-regulated miR-193b-3p could significantly reduce the thoracic aorta pathological damage in AD mice. Conclusion: LncRNA H19 regulated smooth muscle cell function by sponging miR-193b-3p and it participated in the development of AD.
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