The discovery of cancer stem cells and tumor heterogeneity prompted the exploration of additional mechanisms aside from genetic mutations for carcinogenesis and cancer progression. The aim of the present study was to investigate the effect of cell fusion between mesenchymal stem cells and the gastric epithelial cells in tumorigenesis. Cell fusion between cord blood mesenchymal stem cells and human gastric epithelial cells was performed in vitro. Cell scratch and transwell assays were performed to determine migration and invasion abilities of the hybrids. The expressions of epithelial-mesenchymal transition-related proteins and genes were analyzed by immunocytochemistry and real time quantitative PCR. Tumorigenesis of the hybrids was evaluated through in vivo inoculation in nude mice. Hybrids expressed the phenotypes of both donor cells. Aneuploidy was observed in 84.1% of cells. The hybrids showed increased proliferation, migration and invasion abilities compared with the parental cells. In addition, the expression of N-cadherin and vimentin in the hybrids was significantly higher than that of the epithelial cells, and the mRNA expression of the epithelial-mesenchymal transition-related genes, Twist and Slug, in the hybrids was also increased compared with that of the parental epithelial cells. Furthermore, the hybrids formed masses of epithelial origin with glandular structures in BALB/c nude mice. These findings suggest that cell fusion between gastric epithelial cells and mesenchymal stem cells may result in epithelial to mesenchymal transition and malignant transformation.

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 (2004–2015) 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 18–59-year-old patients. LNM rate decreased with age (R² = 0.932, P < .0001), especially women (R² = 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.

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 ( ). 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.

Objective: The 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.Method: The 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.Results: The 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.Conclusion: We 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.