Project description:BackgroundPapillary thyroid carcinoma (PTC) is the most common malignant endocrine tumour, and its incidence and prevalence are increasing considerably. Cellular heterogeneity in the tumour microenvironment is important for PTC prognosis. Spatial transcriptomics is a powerful technique for cellular heterogeneity study.MethodsIn conjunction with a clinical pathologist identification method, spatial transcriptomics was employed to characterise the spatial location and RNA profiles of PTC-associated cells within the tissue sections. The spatial RNA-clinical signature genes for each cell type were extracted and applied to outlining the distribution regions of specific cells on the entire section. The cellular heterogeneity of each cell type was further revealed by ContourPlot analysis, monocle analysis, trajectory analysis, ligand-receptor analysis and Gene Ontology enrichment analysis.ResultsThe spatial distribution region of tumour cells, typical and atypical follicular cells (FCs and AFCs) and immune cells were accurately and comprehensively identified in all five PTC tissue sections. AFCs were identified as a transitional state between FCs and tumour cells, exhibiting a higher resemblance to the latter. Three tumour foci were shared among all patients out of the 13 observed. Notably, tumour foci No. 2 displayed elevated expression levels of genes associated with lower relapse-free survival in PTC patients. We discovered key ligand-receptor interactions, including LAMB3-ITGA2, FN1-ITGA3 and FN1-SDC4, involved in the transition of PTC cells from FCs to AFCs and eventually to tumour cells. High expression of these patterns correlated with reduced relapse-free survival. In the tumour immune microenvironment, reduced interaction between myeloid-derived TGFB1 and TGFBR1 in tumour focus No. 2 contributed to tumourigenesis and increased heterogeneity. The spatial RNA-clinical analysis method developed here revealed prognosis-associated cellular heterogeneity in the PTC microenvironment.ConclusionsThe occurrence of tumour foci No. 2 and three enhanced ligand-receptor interactions in the AFC area/tumour foci reduced the relapse-free survival of PTC patients, potentially leading to improved prognostic strategies and targeted therapies for PTC patients.
Project description:BackgroundFindings of recent studies have demonstrated a rapid increase of the incidence of papillary thyroid carcinoma (PTC), which accounts for nearly 80% of thyroid cancers.ObjectivesThe aim of this study was to explore the association between AXIN2 gene polymorphism and papillary thyroid carcinoma (PTC).Patients and methods106 blood samples (56 PTC patients and 50 healthy controls) were drawn from China-Japan Union Hospital in Jilin province, China, during October 2010 to March 2011. A case-control study was designed to examine the association between AXIN2 and PTC. Seven tag single nucleotide polymorphisms (tag SNPs) in AXIN2 were selected and genotyped. Frequencies of different genotypes and alleles were analyzed between the patients and the controls, using the R × C column contingency table χ(2) test. The possible association of haplotypes constructed by the combined effects of two or more loci with PTC was analyzed through the UNPHASED 3.1.4 program.ResultsRs11655966, rs3923086 and rs7591 of AXIN2 showed significant associations with PTC (P < 0.05). The result of haplotypes analysis showed that rs11655966-rs3923086-rs4791169 had statistically significant differences between the two groups (P < 0.05).ConclusionsTogether with the functions of the target genes, we further elucidated that AXIN2 is associated with papillary thyroid carcinoma in the Chinese Han population.
Project description:The differences in prognosis of papillary thyroid carcinoma (PTC) by sex have been investigated in several previous studies, but the results have not been consistent. In addition, the impact of sex on the clinical and pathological characteristics, especially on central lymph node metastasis (CLNM), still remains unknown. To the best of our knowledge, the impact of sex on PTC has not been investigated in the Chinese PTC population. Therefore, our study retrospectively analysed the data of 1339 patients who were diagnosed with PTC and had received radical surgery at Ningbo Medical Center, Lihuili Hospital. In addition to cancer-specific death, structural recurrence and risk stratification, prognosis was also estimated by using three conventional prognostic systems: AMES (age, distant metastasis, extent, size), MACIS (distant metastasis, age, completeness of resection, local invasion, size) and the 8th version TNM (tumor, lymph node, metastasis) staging system. The clinical and pathological characteristics and above prognostic indexes were compared between male and female PTC patients. The results showed that there were higher rates of non-microcarcinoma PTC (nM-PTC), CLNM, lateral lymph node metastasis (LLNM), advanced disease and bilateral disease, but there was a lower rate of concurrent Hashimoto's thyroiditis (HT) in male PTC patients than in female PTC patients. Additionally, the rate of intermediate-risk, high-risk or advanced disease was higher in male PTC patients. The above findings indicate that PTC in men is a more aggressive disease and may have a worse prognosis; thus, it should be treated with more caution.
Project description:The present study was designed to assess the protein expression of the autophagy-associated genes, Beclin-1 and microtubule-associated protein 1 light chain 3 (LC3)-II, as well as the association with clinicopathological features in papillary thyroid carcinoma (PTC). A total of 50 subjects were recruited, including 50 human PTC samples and paired adjacent noncancerous tissue samples. The protein expression of Beclin-1 and LC3-II was analyzed using immunohistochemistry and western blotting. Beclin-1 and LC3-II expression in PTC tissues significantly reduced compared with normal tissues (P<0.05). Expression of Beclin-1 and LC3-II was associated with lymph node metastasis of PTC (P<0.05), but had no association with age, gender, tumor size, tumor number and Tumor-Node-Metastasis stage (P>0.05). Expression of Beclin-1 and LC3-II were positively correlated (r=0.327;P=0.020) in PTC. In conclusion, the activity of autophagy was declined in PTC; this decrease in autophagic capacity may be associated with tumorigenesis and the development of PTC.
Project description:BACKGROUND:Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer (TC), accounting for more than 80% of all cases. Ferroptosis is a novel iron-dependent and Reactive oxygen species (ROS) reliant type of cell death which is distinct from the apoptosis, necroptosis and pyroptosis. Considerable studies have demonstrated that ferroptosis is involved in the biological process of various cancers. However, the role of ferroptosis in PTC remains unclear. This study aims at exploring the expression of ferroptosis-related genes (FRG) and their prognostic values in PTC. METHODS:A ferroptosis-related gene signature was constructed using lasso regression analysis through the PTC datasets of the Cancer Genome Atlas (TCGA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to investigate the bioinformatics functions of significantly different genes (SDG) of ferroptosis. Additionally, the correlations of ferroptosis and immune cells were assessed through the single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT database. Finally, SDG were test in clinical PTC specimens and normal thyroid tissues. RESULTS:LASSO regression model was utilized to establish a novel FRG signature with 10 genes (ANGPTL7, CDKN2A, DPP4, DRD4, ISCU, PGD, SRXN1, TF, TFRC, TXNRD1) to predicts the prognosis of PTC, and the patients were separated into high-risk and low-risk groups by the risk score. The high-risk group had poorer survival than the low-risk group (p < 0.001). Receiver operating characteristic (ROC) curve analysis confirmed the signature's predictive capacity. Multivariate regression analysis identified the prognostic signature-based risk score was an independent prognostic indicator for PTC. The functional roles of the DEGs in the TGCA PTC cohort were explored using GO enrichment and KEGG pathway analyses. Immune related analysis demonstrated that the most types of immune cells and immunological function in the high-risk group were significant different with those in the low-risk group. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) verified the SDG have differences in expression between tumor tissue and normal thyroid tissue. In addition, cell experiments were conducted to observe the changes in cell morphology and expression of signature's genes with the influence of ferroptosis induced by sorafenib. CONCLUSIONS:We identified differently expressed FRG that may involve in PTC. A ferroptosis-related gene signature has significant values in predicting the patients' prognoses and targeting ferroptosis may be an alternative for PTC's therapy.
Project description:Papillary thyroid carcinomas are the most common thyroid cancers and constitute more than 70% of thyroid malignancies. The most common etiologic factor is radiation, but genetic susceptibility and other factors also contribute to the development of papillary thyroid carcinoma. The most common variants include conventional, follicular variant and tall cell variant. However, many other uncommon variants have been described including oncocytic, columnar cell, diffuse sclerosing and solid forms. Immunohistochemical staining with TTF-1 and thyroglobulin is very useful in confirming the diagnosis of papillary thyroid carcinoma especially in metastatic sites. Markers such as HBME-1 and CITED1 can assist in separating some difficult cases of follicular variants of papillary thyroid carcinomas from follicular adenomas. Molecular studies have shown that the BRAF V600E mutation is found mainly in papillary and anaplastic thyroid carcinomas. Other molecular markers such as HMGA2 and insulin-like growth factor II mRNA binding protein 3 have been used recently as molecular tests to separate papillary thyroid carcinoma and its variants from follicular adenomas and other benign thyroid nodules.
Project description:BackgroundAs a rare but aggressive papillary thyroid carcinoma (PTC) variant, the genetic changes of hobnail variant of PTC (HVPTC) are still unclear.ResultsThe prevalence of HVPTC was 1.69% (18/1062) of all PTC diagnosed in our cohort. 73 samples from 55 patients (17 HVPTC, 26 CPTC, 7 PDTC and 5 ATC) were successfully analyzed using targeted NGS with an 18-gene panel. Thirty-seven mutation variant types were identified among 11 genes. BRAF V600E mutation was the most common mutation, which is present in almost all HVPTC samples (16/17, 94%), most CPTC samples (20/26, 77%), and none of the ATC and PDTC samples. TERT promoter mutation (C228T) was identified in 2 ATC and one HVPTC patient. RAS and TP53 mutation are almost exclusively present among ATC and PDTC samples although TP53 mutation was also observed in 3 HVPTC patients. Six different GNAS mutations were identified among 8 CPTC patients (31%) and none of the HVPTC patients. The only patient who died of disease progression harbored concomitant TERT C228T mutation, BRAF V600E mutation and TP53 mutation.MethodsHVPTC cases were identified from a group of 1062 consecutive surgical specimens diagnosed as PTC between 2000 and 2010. Targeted next-generation sequencing (NGS) was applied to investigate the mutation spectrum of HVPTC, compared to classical PTC (CPTC), poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC).ConclusionAs an aggressive variant of PTC, HVPTC has relatively specific molecular features, which is somewhat different from both CPTC and ATC/PDTC and may underlie its relatively aggressive behavior.
Project description:While the intratumor microbiome has become increasingly implicated in cancer development, the microbial landscape of papillary thyroid carcinoma (PTC) is essentially uninvestigated. PTC is characterized by varied prognosis between gender and cancer subtype, but the cause for gender and subtype-based dissimilarities is unclear. Women are more frequently diagnosed with PTC, while men suffer more advanced-staged PTC. In addition, tall cell variants are more aggressive than classical and follicular variants of PTC. We hypothesized that intratumor microbiome composition distinctly alters the immune landscape and predicts clinical outcome between PTC subtypes and between patient genders. Raw whole-transcriptome RNA-sequencing, Level 3 normalized mRNA expression read counts, and DNA methylation 450 k sequencing data for untreated, nonirradiated tumor, and adjacent normal tissue were downloaded from the Genomic Data Commons (GDC) legacy archive for 563 thyroid carcinoma patients. Microbe counts were extracted using Pathoscope 2.0 software. We correlated microbe abundance to clinical variables and immune-associated gene expression. Gene-set enrichment, mutation, and methylation analyses were conducted to correlate microbe abundance to characterize microbes' roles. Overall, PTC tumor tissue significantly lacked microbes that are populated in adjacent normal tissue, which suggests presence of microbes may be critical in controlling immune cell expression and regulating immune and cancer pathways to mitigate cancer growth. In contrast, we also found that microbes distinctly abundant in tall cell and male patient cohorts were also correlated with higher mutation expression and methylation of tumor suppressors. Microbe dysbiosis in specific PTC types may explain observable differences in PTC progression and pathogenesis. These microbes provide a basis for developing specialized prebiotic and probiotic treatments for varied PTC tumors.
Project description:BackgroundPrimary squamous cell carcinoma of the thyroid (PSCCT) has recently been reclassified as a morphologic pattern of anaplastic thyroid carcinoma (ATC). Consequently, PSCCT and squamous cell carcinoma with papillary thyroid carcinoma (SCC-PTC) were categorized as ATC. However, in terms of clinical characteristics and overall prognosis, whether PSCCT is similar to SCC-PTC has yet to be sufficiently investigated. Therefore, this study aimed to elucidate the differences and similarities between PSCCT and SCC-PTC regarding clinicopathological characteristics and prognosis.MethodsWe retrospectively reviewed the medical records of patients with squamous cell carcinoma of the thyroid in our institution from December 2009 to December 2020. In addition, the publications in CNKI, Wanfang, VIP, PubMed, Embase, Web of Science, and ProQuest databases were systematically searched to collect patient information. According to pathological diagnosis, patients were divided into the PSCCT and SCC-PTC groups, and compared their clinical characteristics, treatment, and prognosis, respectively.Results308 patients in the PSCCT group and 60 patients in the SCC-PTC group were enrolled in the study. There were significant differences in gender, age, T stage, N stage, M stage, symptoms at diagnosis, and TTF-1 expression between the two groups. Patients in the SCC-PTC group with more frequent radioactive iodine therapy, surgery, and less frequent radiotherapy than PSCCT. In addition, PSCCT and SCC-PTC also demonstrated similarities in tracheal invasion, esophageal invasion, CK5/6 expression, TG expression, P53 expression, and chemotherapy frequency. The 3-year overall survival rate of PSCCT (19.1%) was lower than that of SCC-PTC (34.6%). The prognostic factors were different between the two groups. Multivariable analysis shows that the N stage, M stage, radiotherapy, and tracheal invasion were related to the prognosis of PSCCT, while only the T stage was associated with the prognosis in SCC-PTC.ConclusionsClinicopathological characteristics and prognosis were not identical in patients with SCC-PTC and PSCCT. These findings indicated that different clinical treatment and management plans are required for patients with these two types of thyroid cancer.
Project description:Background and objectivePapillary thyroid carcinoma (PTC) is the most common subtype of thyroid cancer, accounting for up to 85-90% of cases, with the best overall prognosis and mostly inert tumors. However, some tumors are aggressive, causing metastasis, recurrence, and other bad outcomes. Preoperative inflammation indices, such as lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and systemic immune inflammation index (SII) in peripheral blood, have recently gained attention as nonspecific markers of inflammatory response in thyroid. In this study, we reviewed the interactions between preoperative inflammatory factors and outcomes in patients with PTC.MethodsThis is a narrative review. We searched for English articles published between January 2014 and December 2023 on PubMed and Web of Science to identify how do these blood indicators affect the prognosis of patients with papillary thyroid cancer.Key content and findingsAll retrievable indicators that have predictive significance for the prognosis of PTC were included, and the prognosis mainly included tumor-node-metastasis (TNM) staging, survival rate, recurrence, clinical and pathological risk factors such as lymph node metastasis (LNM), etc. From the general evidence, the prognostic predictive value of cell count alone was unknown, and low LMR was usually associated with poor prognosis, high NLR and high platelet-to-lymphocyte ratio (PLR) usually indicated poor prognosis.ConclusionsThese minimally invasive, low-cost, and easily obtainable blood indicators provide convenience for precise prognosis management of PTC patients, but many of the findings are conflicting and need to be validated by prospective studies that are more multi-sample, multi-centre and incorporate factors such as age that affect the immune response.