Both anaplastic thyroid cancer (ATC) and papillary thyroid cancer (PTC) originate from thyroid follicular epithelial cells, but ATC has a significantly worse prognosis and shows resistance to conventional therapies. However, clinical trials found that immunotherapy works better in ATC than late-stage PTC. Here, we used single-cell RNA sequencing (scRNA-Seq) to generate a single-cell atlas of thyroid cancer. Differences in ATC and PTC tumor microenvironment components (including malignant cells, stromal cells, and immune cells) leading to the polarized prognoses were identified. Intriguingly, we found that CXCL13 ⁺ T lymphocytes were enriched in ATC samples and might promote the development of early tertiary lymphoid structure (TLS). Last, murine experiments and scRNA-Seq analysis of a treated patient’s tumor demonstrated that famitinib plus anti–PD-1 antibody could advance TLS in thyroid cancer. We displayed the cellular landscape of ATC and PTC, finding that CXCL13 ⁺ T cells and early TLS might make ATC more sensitive to immunotherapy.

(1) Background: The genetic predisposition to papillary thyroid cancer (PTC) is far from clearly elucidated. Rs2292832 is a genetic polymorphism that located in the precursor of mir-149 and has been studied in diverse cancers. Thus far, the role of rs2292832 in PTC tumorigenesis and progression was unclear; (2) Method: Rs2292832 was genotyped in 838 PTCs, 495 patients with thyroid benign tumors (BNs) and 1006 controls in a Chinese Han population. Clinicopathological data was collected and compared. The expression level of mature mir-149 was examined in 55 normal thyroid tissue samples; (3) Results: The CC genotype of rs2292832 was significantly associated with an increased risk of PTC compared with TT homozygote (OR = 1.60, 95% CI: 1.72–2.20, p = 0.003) and TT/TC combined genotype (OR = 1.54, 95% CI: 1.14–2.09, p = 0.005). Rs2292832 is an independent risk factor correlated with tumor invasion (p = 0.006) and higher T stage in PTC patients (p = 0.007), but uncorrelated with short-term disease persistence of PTC. PTC subjects carrying CC genotype have lower mir-149-5p expression than those with TC genotype (p = 0.002). Twelve predicted target genes have been identified by collaboratively using computational tools; (4) Conclusion: Rs2292832 was possibly involved in the susceptibility and local progression of PTC in Chinese patients, by altering the expression level of mir-149-5p and its target genes.

Background: The aim of this study was to develop and validate prognostic nomograms predicting overall (OS) and cancer-specific survival (CSS) of patients with major salivary gland (MaSG) mucoepidermoid carcinoma (MEC). Methods: 1398 MaSG-MEC patients were identified from the Surveillance, Epidemiology and End Results (SEER) database. They were randomly and equally divided into a training cohort (n=699) and a validation cohort (n=699). The best subsets of covariates were identified to develop nomograms predicting OS and CSS based on the smallest Akaike Information Criterion (AIC) value in the multivariate Cox models. The nomograms were internally and externally validated by the bootstrap resampling method. The predictive ability was evaluated by Harrell's Concordance Index (C-index). Results: For the training cohort, eight (age at diagnosis, tumor grade, primary site, surgery, radiation, T, N and M classification) and seven predictors (all the above factors except primary site) were selected to create the nomograms estimating the 3- and 5- year OS and CSS, respectively. C-index indicated better predictive performance of the nomograms than the 7th AJCC staging system, which was confirmed by both internal (via the training cohort: OS: 0.888 vs 0.785, CSS: 0.938 vs 0.821) and external validation (via the validation cohort: OS: 0.844 vs 0.743, CSS: 0.882 vs 0.787). The calibration plots also revealed good agreements between the nomogram-based prediction and observed survival. Conclusions: We have proposed and validated the nomograms predicting OS and CSS of MaSG-MEC. They are proved to be of higher predictive value than the AJCC staging system and may be adopted in future clinical practice.

Background: Patients with anaplastic thyroid cancer (ATC), which is among the deadliest of all cancers, often have a poor response to traditional therapies. Currently, the role of long non-coding RNAs (lncRNAs) in ATC carcinogenesis is unclear. In this study, we analyzed the lncRNA expression profile of ATC with the aim of identifying potential molecular targets for treatment of the disease. Methods: Whole transcriptome sequencing of three ATC and two normal thyroid (NT) samples was performed, and the lncRNA expression profile of ATC was analyzed. Original data as well as datasets deposited in the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were used for clinical validation. Cell proliferation, Transwell, and apoptosis assays were performed using ATC cell lines. Gene Ontology (GO) and gene set enrichment analyses (GSEA) were performed to determine the dysregulated pathways. Results: Whole transcriptome sequencing revealed 182 lncRNAs to be differentially expressed in ATC. One of the lncRNAs, mitotically associated long non-coding RNA (MANCR; LINC00704), was significantly overexpressed in ATC cell lines and patient samples compared with NT and papillary thyroid cancer (PTC). MANCR depletion in ATC cells significantly inhibited cancer cell proliferation and invasion, and induced apoptosis. By further analyzing the transcriptome data, we identified 451 genes co-expressed with MANCR. GO and GSEA showed that the top dysregulated pathways were related to mitosis and cell cycle. Conclusions: MANCR is a tumor promoter in ATC, and its role in carcinogenesis is possibly associated with cell cycle regulation. Because MANCR expression is minimal in most normal tissues, it may serve as a potential target in the future treatment of ATC.