Background: The goal of this study was to identify the clinicopathological factors of co-existing papillary thyroid cancer (PTC) in patients with Hashimoto’s thyroiditis (HT) and provide information to aid in the diagnosis of such patients. Methods: This study included 6109 patients treated in a university-based tertiary care cancer hospital over a 3-year period. All of the patients were categorised based on their final diagnosis. Several clinicopathological factors, such as age, gender, nodular size, invasive status, central compartment lymph node metastasis (CLNM) and serum thyroid-stimulating hormone (TSH) level, were compared between the various groups of patients. Results: There were 653 patients with a final diagnosis of HT. More PTC was found in those with HT (58.3%; 381 of 653) than those without HT (2416 of 5456; 44.3%; p < 0.05). The HT patients with co-occurring PTC were more likely to be younger, be female, have smaller nodules and have higher TSH levels than those without PTC. A multivariate analysis indicated that the presence of HT and higher TSH levels were risk factors for a diagnosis of PTC. In the PTC patients, the presence of HT or another benign nodule was a protective factor for CLNM, whereas no significant association was found for TSH levels. Conclusion: PTC and HT have a close relationship in this region of highly prevalent HT disease. Based on the results of our study, we hypothesise that long-term HT leads to elevated serum TSH, which is the real risk factor for thyroid cancer.

(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: Firstly, 5-hydroxytryptamine G-protein-coupled receptors (HTGPCRs) are a family of 13 genes associated with cancer progression. Nevertheless, a comprehensive understanding of HTGPCRs in cancer remains largely lacking. Method: We tested the gene expression levels and prognostic values for the HTGPCRs in relation to pan-cancer. A subsequent analysis examined the relationships among HTGPCR expression and clinical characteristics, immune subtypes, stemness scores, tumor microenvironments (TMEs), single-cell analyses, and drug sensitivity. Result: A significant difference in HTGPCR expression was found between normal tissues and tumors. HTR1D/2C expressed higher levels in breast invasive carcinoma (BRCA), colon adenocarcinoma, and liver hepatocellular carcinoma. HTGPCR gene expression was correlated with prognosis in many cancers. HTR1D/2C were associated with poorer overall survival for head and neck squamous cell carcinoma. In addition, HTGPCR expression correlated significantly with the stemness scores of RNA and DNA, TMB, and MSI, as well as stromal and immune scores of pan-cancer patients. Additionally, the expression of HTR2A/2B/7 was correlated significantly with immune cells and immune checkpoint genes in a variety of cancers, such as BRCA, brain lower-grade glioma, and lung adenocarcinoma. Immune regulation and TME were both regulated by HTGPCRs. Using single-cell analysis, we found that the gene set of HTGPCRs correlated with many cancer-related functional states in retinoblastoma. Moreover, drug sensitivity and HTR4 were significantly correlated. Furthermore, we validated results in breast cancer and found knockdown of HTR1D inhibited breast cancer cell growth and metastasis. Conclusion: As prognostic indicators, HTGPCRs hold considerable promise and offer insights into the therapeutic targets for malignancy.

The recruitment and polarization of tumor-associated macrophages (TAMs) play a pivotal role in shaping the immunosuppressive tumor microenvironment in breast cancer. Interleukin-1 receptor accessory protein (IL1RAP), a critical co-receptor for IL-1 family cytokines, is emerging as a potential regulator of macrophage function, though its specific role in TAM biology remains to be explained. In this study, we investigated the impact of IL1RAP on macrophage recruitment and M2-like polarization. Initial bioinformatics analysis of public databases revealed a significant correlation between elevated IL1RAP expression in macrophages and signatures of immune suppression and poor prognosis in breast cancer. To functionally validate these findings, we performed IL1RAP knockdown in a murine macrophage cell line. Our results demonstrated that IL1RAP deficiency markedly impaired the migratory capacity of macrophages towards classic chemotactic stimuli. Furthermore, under M2-polarizing conditions, IL1RAP-knockdown macrophages exhibited a significantly attenuated M2 phenotype, as evidenced by the decreased expression of canonical M2 markers (e.g., Arg1, Mrc1) and reduced functional outputs. Collectively, our integrated approach combining bioinformatics and in vitro experimentation identifies IL1RAP as a novel regulator that potentiates both the recruitment and the M2 polarization of macrophages. These findings suggest that targeting the IL1RAP pathway could represent a promising therapeutic strategy for reprogramming the tumor-immune microenvironment by limiting pro-tumoral macrophage infiltration and polarization.

Upstream binding transcription factor (UBTF) is a nuclear transcription factor implicated in ribosome biogenesis, yet its pancancer relevance and immunological associations remain incompletely understood. We integrated datasets from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Human Protein Atlas (HPA), Cancer Cell Line Encyclopedia (CCLE), and cBioPortal databases to characterize UBTF expression, genomic alterations, and prognostic value across 33 cancer types. Immune microenvironment analyses were performed using ESTIMATE and multiple deconvolution algorithms. CRISPR-Cas9–mediated UBTF depletion was conducted in breast invasive carcinoma (BRCA) cell lines to evaluate functional roles. UBTF was broadly upregulated in multiple tumors with recurrent copy number gains. Survival analyses revealed cancer type–dependent prognostic associations. UBTF expression correlated with immune/stromal contexture, checkpoint features, and predicted immunotherapy response. In BRCA, UBTF depletion reduced proliferation and migration while increasing apoptosis. A UBTF-related prognostic signature effectively stratified patient outcomes and was associated with immune infiltration and predicted immunotherapy response. UBTF represents a pancancer biomarker linked to tumor immunity, with validated functional significance in BRCA and potential utility for risk stratification.

Immune checkpoint blockade benefits only a minority of patients with triple-negative breast cancer (TNBC), and the tumour-intrinsic programmes that establish its immunosuppressive microenvironment remain poorly defined. Pyrimidine metabolism supplies nucleotides and one-carbon units in malignant cells, but whether it shapes the immune microenvironment is unknown. Integrating single-cell, bulk breast cancer transcriptomics with Xenium spatial transcriptomics, DTYMK knockdown, tumour-conditioned-medium co-culture and folate rescue, we found that pyrimidine pathway activity was elevated in the malignant epithelium of TNBC, within which we identified Epi4, a high-potency subpopulation coupling pyrimidine and folate metabolism and predicted to export folate. Furthermore, this folate was predicted to be taken up by FOLR2⁺ tumour-associated macrophages (TAMs) and was associated with S-adenosylmethionine(SAM)-dependent methylation signatures and MAFB activity. Spatially, Epi4 and FOLR2⁺ TAMs co-localised at the tumour–stroma margin, a region of reduced T-cell density. DTYMK depletion reduced tumour fitness and attenuated folate-mediated macrophage reprogramming, which was largely restored by exogenous folate. Here, we therefore identify a DTYMK–folate–MAFB axis in which tumour metabolic rewiring is associated with epigenetic reprogramming of macrophages.