Prognosis Of Thyroid Cancer Patients Research Articles

SPRED3 regulates the NF-κB signaling pathway in thyroid cancer and promotes the proliferation

SPRED3 (Sprouty-related EVH1 domain containing 3) mutants are depicted in various cancers, however, nothing is known about its biofunction in thyroid cancer (THCA). Bioinformatic analyses were conducted to ascertain the level of SPRED3 expression in THCA tissues and its importance in the prognosis of THCA patients. Flag-SPRED3 plasmid and SPRED3-knockout vector were developed to overexpress or deplete the SPRED3 expression in THCA cells. The function of SPRED3 on THCA cell proliferation was examined using the colony formation assay and CCK8 assay. The effect of SPRED3 expression on the transcriptional activity of NF-κB was also examined using luciferase reporter assays. High SPRED3 expression was associated with unfavorable clinical outcomes, advanced tumor characteristics, and traditional molecular markers of papillary thyroid cancer in THCA patients. Genetic analysis revealed differences in mutation rates in key genes between SPRED3-high and SPRED3-low THCA cases. It is also revealed that SPRED3 influenced the immune microenvironment, with increased stromal and immune scores and altered immune cell infiltration. Functionally, SPRED3 overexpression enhanced THCA cell viability and colony formation, while its depletion reduced cell growth and proliferation. In vivo experiments in mice confirmed the inhibitory effect of SPRED3 depletion on tumor growth. Mechanically, we found that SPRED3 activated the NF-κB signaling. For the first time, we found that SPRED3 promotes THCA cell proliferation via the NF-κB signaling pathway. This finding may provide insight into SPRED3’s prognostic potential in thyroid cancer and provide the rationale for SPRED3-targeted druggable interventions.

Brain Metastases from Thyroid Carcinoma: Prognostic Factors and Outcomes.

Intracranial metastases from thyroid cancer are rare. Although the prognosis of thyroid cancer patients is generally favorable, the prognosis of patients with intracranial metastases from thyroid cancer has been considered unfavorable owing to lower survival rates among such patients compared to those without intracranial involvement. Many questions about their management remain unclear. The aim of the present study was to analyze the characteristics, treatment modalities, and outcomes of patients with brain metastases from thyroid cancer. Among 4320 patients with thyroid cancer recorded in our institutional database over a 30-year period, the data of 20 patients with brain metastasis were retrospectively collected and analyzed. The clinical characteristics, histological type of primary cancer and metastatic brain tumor, additional previous distant metastasis, treatment modalities, locations and characteristics on radiologic findings, time interval between the first diagnosis of primary thyroid cancer and brain metastasis, and survival were analyzed. Among our patient cohort, the mean age at initial diagnosis was 59.3 ± 14.1 years, and at the manifestation of diagnosis of cerebral metastasis, the mean age was found to be 64.8 ± 14.9 years. The histological types of primary thyroid cancer were identified as papillary in ten patients, follicular in seven, and poorly differentiated carcinoma in three. The average interval between the diagnosis of thyroid cancer and brain metastasis was 63.4 ± 58.4 months (range: 0-180 months). Ten patients were identified as having a single intracranial lesion, and ten patients were found to have multiple lesions. Surgical resection was primarily performed in fifteen patients, and whole-brain radiotherapy, radiotherapy, or tyrosine kinase inhibitors were applied in the remaining five patients. The overall median survival time was 15 months after the diagnosis of BMs from TC (range: 1-252 months). Patients with thyroid cancer can develop brain metastasis even many years after the diagnosis of the primary tumor. The results of our study demonstrate increased overall survival in patients younger than 60 years of age at the time of diagnosis of brain metastasis. There was no difference in survival between patients with brain metastasis from papillary carcinoma and those with follicular thyroid carcinoma.

Increased FGF2 expression promotes immune cell infiltration and correlates with an unfavorable prognosis in thyroid cancer

To delve into the expression and functions of FGF2 in patient with thyroid cancer (THCA), we conducted a systematic analysis of the association of FGF2 with immune cell infiltration, and prognosis in THCA patients. The transcription and protein levels, methylation, and biological properties of FGF2 were examined, along with its correlation with prognosis and immune cell infiltration in THCA patients using online databases UALCAN, Human Protein Atlas, Kaplan-Meier Plotter, DNMIVD, cBioPortal, GEPIA, Metascape, Linkedomics and TIMER. Clinical samples were collected for Western blot analyses. FGF2 was substantially overexpressed in the tumor group and shown correlations with age, tumor histology, nodal metastasis, and cancer stages. Moreover, higher expression of FGF2 (HR = 3.42, 95 % CI:1.57-7.44, p = 0.00099) was greatly correlated with poorer relapse-free survival in THCA patients, particularly in female patients. FGF2 methylation level was increased in the tumor group (p = 1.29E-6), and higher methylation levels of FGF2 were positively correlated with the poorer progression-free interval in THCA patients (p = 0.015). FGF2 mutations were markedly associated with shorter disease-free survival, with a mutation rate of 6 % among the total 498 THCA patients. FGF2 functions were potentially related to cell adhesion, cytokine-cytokine receptor interaction and angiogenesis. FGF2 expression showed positive correlations with the infiltration of B cells (Cor = 0.569, p = 1.04e-42), CD4+ T cells (Cor = 0.555, p = 9.43e-41), macrophages (Cor = 0.438, p = 2.94e-42), neutrophils (Cor = 0.578, p = 9.354e-45), and dendritic cells (Cor = 0.591, p = 5.00e-47). FGF2 is a potential prognostic marker in THCA patients, with its functions possibly related to cell adhesion, interaction of the cytokine-cytokine receptor, angiogenesis, and the promotion of multiple immune cell infiltration.

IRX5's influence on macrophage polarization and outcome in papillary thyroid cancer.

With a rise in recent years, thyroid cancer (TC) is the most prevalent hormonal cancer worldwide. It is essential to investigate the inherent variability at the molecular level and the immune environment within tumors of various thyroid cancer subtypes in order to identify potential targets for therapy and provide precise treatment for patients with thyroid adenocarcinoma. First, we analyzed the expression of IRX5 in pan-cancer and papillary thyroid carcinoma by bioinformatics methods and collected paired samples from our center for validation. Subsequently, we analyzed the significance of IRX5 on the prognosis and diagnosis of PTC. Next, we explored the possible mechanisms by which IRX5 affects the prognosis of thyroid cancer patients by GO/KEGG enrichment analysis, and further investigated the effect of IRX5 on immune infiltration of thyroid cancer. Ultimately, by conducting experiments on cells and animals, we were able to show how IRX5 impacts the aggressive characteristics of thyroid cancer cells and its influence on macrophages within the immune system of thyroid cancer. In 11 malignant tumors, including PTC, IRX5 is overexpressed and associated with a poor prognosis. IRX5 may affect the prognosis of PTC through embryonic organ development, ossification, mesenchyme development, etc. Increased IRX5 expression decreases the presence of cytotoxic and Th17 cells in papillary thyroid cancer. IRX5 was highly expressed in different PTC cell lines, such as K-1 and TPC-1. Silencing IRX5 effectively halted the growth and movement of PTC cells while also decreasing M2 polarization and enhancing M1 polarization in tumor-associated macrophages. IRX5 could impact the outlook of individuals with PTC by stimulating the shift of macrophages to M2 in the immune surroundings of thyroid cancer growths, suggesting a potential new focus for treating thyroid cancer, particularly through immunotherapy.

LncRNAs associated with lymph node metastasis in thyroid cancer based on TCGA database

ObjectiveLong non-coding RNA (lncRNA), especially RNA associated with lymph node metastasis, plays an important role in the development of cancer. Identifying metastasis related lncRNAs and exploring their clinical significance can guide the treatment and prognosis of thyroid cancer patients. MethodsRNA expression and clinical data of thyroid cancer was derived from The Cancer Genome Atlas (TCGA) database, while the survival data was obtained from the ULCAN database. R language and SPSS software were used to analyze the correlation between lncRNA and lymph node metastasis of thyroid cancer and the lncRNAs associated with lymph node metastasis were screened. Result10 lncRNAs showed significant differential expression in thyroid cancer with and without lymph node metastasis. Four lncRNAs (LRRC52-AS1, AP002358.1, AC004847.1, and AC254633.1) were overexpressed in metastatic thyroid cancer, while six lncRNAs (SLC26A4-AS1, LINC01886, LINC01789, AF131216.3, AC062015.1, and AL031710.1) were underexpressed. The expression levels of these lncRNAs were associated with the clinical staging of tumors. Cox regression analysis further showed that elevated expression levels of AP002358.1 and LRRC52-AS1 were associated with poor prognosis in patients with thyroid cancer. In addition, analysis of the UALCAN database indicated that these two lncRNAs were significantly overexpressed in thyroid cancer compared to other cancers, and the expression levels of AF131216.3 and AL031710.1 were associated with progression-free survival in thyroid cancer patients. ConclusionThese lncRNAs may play crucial roles in the development and progression of thyroid cancer and could serve as potential markers for predicting tumor metastasis, clinical stage, and patient prognosis.

METTL3 regulates thyroid cancer differentiation and chemosensitivity by modulating PAX8.

Background: Thyroid cancer (TC) is a common endocrine cancer with a favourable prognosis. However, poor patient prognosis due to TC dedifferentiation is becoming an urgent challenge. Recently, methyltransferase-like 3 (METTL3)-mediated N6 -methyladenosine (m6A) modification has been demonstrated to play an important role in the occurrence and progression of various cancers and a tumour suppressor role in TC. However, the mechanism of METTL3 in TC remains unclear. Methods: The correlation between METTL3 and prognosis in TC patients was evaluated by immunohistochemistry. Mettl3fl/flBrafV600ETPO-cre TC mouse models and RNA-seq were used to investigate the underlying molecular mechanism, which was further validated by in vitro experiments. The target gene of METTL3 was identified, and the complete m6A modification process was described. The phenomenon of low expression of METTL3 in TC was explained by identifying miRNAs that regulate METTL3. Results: We observed that METTL3 expression was negatively associated with tumour progression and poor prognosis in TC. Mechanistically, silencing METTL3 promoted the progression and dedifferentiation of papillary thyroid carcinoma (PTC) both in vivo and in vitro. Moreover, overexpressing METTL3 promoted the sensitivity of PTC and anaplastic thyroid cancer (ATC) cells to chemotherapeutic drugs and iodine-131 (131I) administration. Overall, the METTL3/PAX8/YTHDC1 axis has been revealed to play a pivotal role in repressing tumour occurrence, and is antagonized by miR-493-5p.

NOLC1 was identified as a tumor suppressor gene in thyroid cancer and correlated with prognosis by bioinformatics.

Thyroid cancer (THCA) is the most common endocrine malignancy, mainly affecting women's unilateral glandular lobes. However, for relapsed and distant metastasis of THCA patients, the existing early diagnosis and treatment methods were still insufficient, and a new method was urgently needed to diagnose and treat them. Nucleolar and coiled-body phosphoprotein 1 (NOLC1) was one of the most phosphorylated proteins in the cell, which was located mainly in the nucleolus. In addition, more and more studies have confirmed that NOLC1 plays a crucial role in various pathological processes, such as the occurrence and progression of cancer and viral infection. A previous study showed that NOLC1, as a member of RNA-binding protein, was significantly correlated with the prognosis of THCA patients. However, further exploration of NOLC1 in THCA is limited. To further explore the role of NOLC1 in THCA, we conducted expression and survival prognosis analysis of NOLC1 using multiple databases. We also evaluated the correlation between NOLC1 gene expression and clinical characteristics of THCA patients. Furthermore, we analyzed the relationship between NOLC1 and other genes, followed by enrichment analysis to investigate its metabolic pathways and molecular metabolism processes. Additionally, we examined the association between immune cell infiltration in tumor microenvironment and NOLC1. Notably, through vitro experiments, we confirmed the tumor suppressive effect of NOLC1 on the proliferation and migration of human THCA cells, providing evidence for clinical diagnosis of THCA. Furthermore, we confirmed the tumor suppressive effect of NOLC1 in vivo xenograft assay. To sum up, our results suggest that NOLC1 is a tumor suppressor gene for THCA.

Osseous Metastases in Thyroid Cancer: Unveiling Risk Factors, Disease Outcomes, and Treatment Impact.

Bone is the second most common site of metastasis in patients with thyroid cancer (TC) and dramatically impacts overall survival and quality of life with no definitive cure, yet there is no extensive study of the demographic and clinical risk factors in the recent literature. Data regarding 120,754 TC patients with bone metastasis were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate analyses were used to identify the risk factors of bone metastasis occurring in various histologies of TC. Cox regression was performed to analyze the influence of bone metastasis on overall survival. Hazard ratios were computed to analyze the association between bone metastasis and the primary outcomes. Of the 120,754 records collected from the SEER database from 2000 to 2019, 976 (0.8%) presented with bone metastasis, with occurrence being the greatest in patients of age ≥ 55 years (OR = 5.63, 95%CI = 4.72-6.71), males (OR = 2.60, 95%CI = 2.27-2.97), Blacks (OR = 2.38, 95%CI = 1.95-2.9) and Asian or Pacific Islanders (OR = 1.90, 95%CI = 1.58-2.27), and single marital status. TC patients presenting with bone metastasis (HR = 2.78, 95%CI = 2.34-3.3) or concurrent bone and brain metastases (HR = 1.62, 95%CI = 1.03-2.55) had a higher mortality risk. Older age, gender, race, and single marital status were associated with bone metastasis and poorer prognosis in TC patients at initial diagnosis. Understanding such risk factors can potentially assist clinicians in making early diagnoses and personalized treatment plans, as well as researchers in developing more therapeutic protocols.

Identification of a Novel Cuproptosis-Related Gene Signature and Integrative Analyses in Thyroid Cancer

Cuproptosis is a novel programmed cell death that depends on copper. The role and potential mechanism of cuproptosis-related genes (CRGs) in thyroid cancer (THCA) are still unclear. In our study, we randomly divided THCA patients from the TCGA database into a training set and a testing set. A cuproptosis-related signature consisting of six genes (SLC31A1, LIAS, DLD, MTF1, CDKN2A, and GCSH) was constructed using the training set to predict the prognosis of THCA and was verified with the testing set. All patients were classified into low- and high-risk groups according to risk score. Patients in the high-risk group had a poorer overall survival (OS) than those in the low-risk group. The area under the curve (AUC) values for 5 years, 8 years, and 10 years were 0.845, 0.885, and 0.898, respectively. The tumor immune cell infiltration and immune status were significantly higher in the low-risk group, which indicated a better response to immune checkpoint inhibitors (ICIs). The expression of six cuproptosis-related genes in our prognostic signature were verified by qRT-PCR in our THCA tissues, and the results were consistent with TCGA database. In summary, our cuproptosis-related risk signature has a good predictive ability regarding the prognosis of THCA patients. Targeting cuproptosis may be a better alternative for THCA patients.

Omics sciences and precision medicine in thyroid cancer.

Thyroid cancer, a heterogeneous disease originating from the thyroid gland, stands as the predominant endocrine malignan-cy worldwide. Despite advances in diagnosis and treatment, some patients still experience recurrence and mortality, which highlights the need for more personalized approaches to treatment. Omics sciences, encompassing genomics, transcriptomics, proteomics, and metabolomics, offer a high-throughput and impartial methodology for investigating the molecular signatures of thyroid cancer. In the course of this review, we have adopted a focu-sed research strategy, meticulously selecting the most pertinent and emblematic articles related to the topic. Our methodology included a systematic examination of the scientific literature to guarantee a thorough and precise synthesis of the existing sources. These techniques enable the identification of molecular markers that can aid in diagnosis, prognosis, and treatment selection. As an illustration, through genomics studies, numerous genetic alterations commonly discovered in thyroid cancer have been identified, such as mutations in the BRAF and RAS genes. Through transcriptomics studies, distinctively expressed genes in thyroid cancer have been uncovered, playing roles in diverse biological processes, including cell proliferation, invasion, and metastasis. These genes can serve as potential targets for novel therapies. Proteomics studies have unveiled differentially expressed proteins intricately involved in thyroid cancer pathogenesis, presenting promising biomarkers for early detection and disease progression monitoring. Metabolomics studies have identified alterations in metabolic pathways linked to thyroid cancer, offering promising avenues for potential therapeutic targets. Precision medicine in thyroid cancer involves the integration of omics sciences with clinical data to develop personalized treatment plans for patients. Employing targeted therapies guided by molecular markers has exhibited promising outcomes in enhancing the prognosis of thyroid cancer patients. Notably, those with advanced hyroid cancer carrying BRAF mutations have displayed substantial responses to specific targeted therapies, such as vemurafenib and dabrafenib.

Circ_0008792 Prevents Against the Deterioration of Thyroid Cancer Through Regulating IGFBP5

To detect the expression of circ_0008792 in thyroid cancer (TC) tissues and cell lines, and to explore the regulatory effect of circ_0008792 on TC progression. Relative levels of circ_0008792 and IGFBP5 in TC and paracancerous tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The influences of circ_0008792 and IGFBP5 on pathology and prognosis of TC patients were analyzed. After intervening circ_0008792 level by transfection, changes in proliferative and migratory abilities of BHP5-16 and TPC cells were analyzed by cell counting kit-8 (CCK-8) and transwell assay, respectively. The interaction between circ_0008792 and IGFBP5 was explored by dual-luciferase reporter assay. In vivo xenograft model of TC was constructed in nude mice. Co-regulation of circ_0008792 and IGFBP5 on in vitro and In vivo TC progression was respectively analyzed. circ_0008792 was lowly expressed in TC tissues. TC patients overexpressing circ_0008792 had a relatively well outcome, manifesting as earlier tumor staging, lower rate of lymphatic metastasis and higher overall survival in comparison to whom expressing low level of circ_0008792. Overexpression of circ_0008792 in TC cells attenuated proliferative and migratory abilities, and knockdown of circ_0008792 yielded the opposite results. IGFBP5 was the target gene binding circ_0008792, which was negatively correlated to circ_0008792 in TC tissues. circ_0008792 overexpression attenuated proliferative and migratory abilities in TC cells, and slowed down In vivo growth of TC by targeting IGFBP5. circ_0008792 is lowly expressed in TC, and its level is correlated to tumor staging, lymphatic metastasis rate and overall survival of TC. It inhibits proliferative and migratory potentials in TC cells by regulating IGFBP5.

Serum Sialyl Fibronectin Is an Indicator of Good Prognosis in Thyroid Cancer.

Sialyl-fibronectin (S-FN), a type of glycoprotein like Sialyl Lewisa and MAC1 thyroid cancer biomarkers, has been found to be expressed in thyroid cancer. In this study, we examined the usefulness of serum S-FN as a biomarker, as well as prognostic factor in various tumors including thyroid cancer. Using the MoAb JT-95, an ELISA kit was created and S-FN levels in sera (blood S-FN) of a total of 182 cases were investigated. Analysis included 63 cases of thyroid cancer, 33 cases of thyroid benign tumors, 7 cases of parathyroid benign tumors, and 79 cases of breast cancer. The incidence of blood S-FN-positive cases was 24 (38.0%) in 63 examined patients with thyroid cancer. Out of 40 examined benign neck tumor cases, 16/40 (40%) were S-FN-positive. Out of 79 examined breast cancer cases, 20/79 (25.3%) were S-FN-positive, with significant differences between thyroid and breast cancer cases (p=0.007). Regarding the association of blood S-FN expression and prognosis in thyroid cancer, there was a significant difference between 39 blood S-FN-negative cases and 15 recurrent or metastatic cases in terms of progression and pathological factors: tumor size, lymph node metastasis, extra-membrane infiltration, and clinical stage. All 63 assessed thyroid cancer cases also had a significant difference in these factors. There were no significant differences between these factors in the 24 blood S-FN-positive thyroid cancer cases. In cases of recurrent metastasis, intravascular cells were observed in all recurrent metastasis patients of both groups. Regarding staining of intravascular infiltrating cells, recurrent metastasis appeared at a higher rate in cases with S-FN-negative infiltrating cells. S-FN presence in blood can be used as an indicator of good prognosis in thyroid cancer patients.

IL2RA+VSIG4+ tumor-associated macrophage is a key subpopulation of the immunosuppressive microenvironment in anaplastic thyroid cancer

Extensive infiltration of tumor-associated macrophages was correlated poor prognosis in anaplastic thyroid cancer (ATC). However, the heterogeneity and characteristics of the ATC-associated macrophages (ATAMs) in ATC remain far from clear. We combined single-cell RNA-sequencing analysis and gene expression microarray datasets to assess the molecular signature of ATAMs. Compared with normal thyroid-associated macrophages (NTAMs), 778 differentially expressed genes (DEGs) significantly changed in ATAMs compared with NTAMs. These DEGs were correlated with oxidative phosphorylation (M2 phenotype) and phagocytosis (M1 phenotype). Moreover, ATAMs highly expressed pro-tumor genes associated with angiogenesis, fibrosis, metalloprotease activity, and metastasis. Notably, we identified one ATC-specific subset, IL2RA+ VSIG4+ ATAMs, co-expressed M1 and M2 markers. The infiltration of IL2RA+ VSIG4+ ATAMs showed strong correlation with BRAF and RAS signaling, and its high infiltration was associated with favorable prognosis in thyroid-cancer patients. IL2RA+ VSIG4+ ATAMs were associated with increased tumor-infiltrating lymphocytes (B cells, CD8+ T cells, Tregs). IL2RA+ VSIG4+ ATAMs interacted with CD8+ T cells and Tregs through immune checkpoints (such as LGALS9_HAVCR2), cytokines (such as CXCL10_CXCR3), and receptors (such as CSF1R_CSF1), thereby forming an immunosuppressive microenvironment. Multiplex immunohistochemistry staining and coculture experiment confirmed that ATC cancer cells were able to induce the polarization of IL2RA+ VSIG4+ ATAMs. Besides, we identified several novel ATC-specific immune checkpoint genes including the immunosuppressive molecule VSIG4, LAIR1, and LILRB2. Expression of VSIG4 was also significantly correlated with tumor-infiltrating lymphocytes (B cells, CD8+ T cells, Tregs). In conclusion, our study revealed an ATC-specific ATAM subset with bifunctional phenotype, which provided a comprehensive insight to delineate the molecular characteristics of ATC-associated macrophages.

Epithelial-to-mesenchymal transition of circulating tumor cells and CD133 expression on predicting prognosis of thyroid cancer patients.

The present study aimed to explore the epithelial-to-mesenchymal transition of circulating tumor cells (CTCs) and CD133 expression in determining the prognosis of patients with thyroid cancer. It enumerated different CTC subtypes and analyzed CD133 gene expression in patients with thyroid cancer to evaluate the relationship between CTC number and thyroid cancer prognosis. In total 394 patients with thyroid cancer were enrolled. Among these, 270 cases had papillary thyroid cancer (PTC), 60 had follicular thyroid cancer (FTC), 30 had medullary thyroid cancer (MTC), 15 had poorly differentiated thyroid cancer, 19 had anaplastic thyroid cancer and 10 had non-malignant thyroid nodules based on their histopathological characteristics. CTC cell counts were determined by CanPatrol CTC capture technique before treatment. The present study also performed reverse transcription-quantitative PCR for CD133 gene expression and evaluated the relationship between CD133 expression and clinical pathology. A total of 330 cases of enrolled patients were classified as differentiated thyroid cancer, which included PTC and FTC. Their prognosis was excellent. The positivity rate of CTCs at diagnosis was 95.5%. The data of the present study showed that early recurrence and metastasis rates in PTC and FTC patients with >6 CTCs and positive mesenchymal circulating tumor cells (MCTCs) were significantly higher than those in patients with <6 CTCs and MCTCs. It was also found that those patients with >6 CTCs and MCTCs had shorter overall survival. In addition, CD133 levels in patients with thyroid cancer were strongly associated with the differentiation grades of thyroid cancers. The detection of >6 CTCs and positive MCTCs in patients with differentiated thyroid cancer was an excellent biomarker for predicting the prognosis of patients. CD133 expression was also identified as a good biomarker for thyroid cancer differentiation.

Impact of Lung Metastasis versus Metastasis of Bone, Brain, or Liver on Overall Survival and Thyroid Cancer-Specific Survival of Thyroid Cancer Patients: A Population-Based Study.

Simple SummaryPatients with thyroid cancer have different survival rate based on their cancer type and the organs affected by the metastases. About 88% of the patients with follicular thyroid cancer are still alive 15 years after diagnosis. Still, some patients will develop metastasis, and the location of the metastases could indicate patients with more aggressive disease.We investigate the impact of lung metastasis versus metastasis of bone, brain, or liver on overall survival (OS) and thyroid cancer-specific survival (TCSS) in patients with thyroid cancer (TC). Therefore, de-identified SEER 18 registry data of primary TC patients diagnosed between 2010 and 2016 were analyzed. The primary outcome was the prognosis of TC patients with lung metastasis compared with other sites. The secondary outcomes included the prognosis comparison between patients with and without surgery and between single and multiple metastasis sites. Isolated lung metastasis was associated with worse OS and TCSS than bone metastasis (both p < 0.05) and was associated with worse OS than liver metastasis (p = 0.0467). Surgery performed either for the primary or distant site was associated with better OS and TCSS in patients with metastasis of lung or bone (p < 0.05). Isolated lung metastasis was related to better OS and TCSS than lung–liver, lung–brain, and lung–other multiple metastases. The multivariable analysis revealed that age < 55 years, surgery to the primary site, and to the distant site(s) were associated with better outcomes, while T4 and Tx were associated with worse outcomes. Nevertheless, it revealed that the other race (i.e., any race other than white, black, or unknown) and male gender were associated with better TCSS only (p < 0.05). Isolated lung metastasis is associated with a worse prognosis in TC patients compared with bone or liver metastasis. Surgery performed either for the primary or distant site(s) is associated with better survival outcomes in TC patients with metastasis of lung or bone.

NOD1 activation promotes cell apoptosis in papillary thyroid cancer

BackgroundNOD1 can promote or inhibit different types of cancers, suggesting that NOD1 functions in the progression of cancers dependent on the tumour environment. However, the expression and mechanisms of NOD1 during papillary thyroid carcinoma (PTC) progression remain unclear. MethodsTo investigate the role of NOD1 in PTC development and apoptosis, we detected NOD1 expression in three cell lines and surgical specimens from patients with PTC using immunohistochemistry, quantitative real-time PCR (Q-PCR) and Western blotting; we studied the biological functions of NOD1 by loss-of-function analysis of TPC-1 and BCPAP cells and the effect of NOD1 on the progression of PTC in terms of cell proliferation and apoptosis induced by tumour necrosis factor alpha (TNF-α), Fas ligand (Fas L), tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) or Ala-γGlu-diaminopimelic acid (TriDAP) in the presence of cycloheximide (CHX) and determined its underlying molecular mechanism using PTC cell lines in vitro and mouse xenograft models in vivo. ResultsIncreased expression of NOD1 is correlated with an improved prognosis in thyroid cancer patients. We also found that NOD1 expression was markedly upregulated in PTC cells compared to normal epithelial cells. NOD1 knockdown significantly promoted the proliferation of PTC cells in vitro, while activation of NOD1 signalling promoted PTC cell apoptosis; NOD1-induced apoptosis depends on the activation of caspase-3 and caspase-9 although the RIP2/TAK1 and MAPK pathways in PTC cells. ConclusionsThis study demonstrates that NOD1 is a predictive biomarker for PTC and that PTC cell apoptosis is induced by activation of NOD1 via the RIP2/TAK1 and MAPK pathways. The above results may provide a new perspective on targeting NOD1 signalling for the treatment of PTC, which deserves further investigation.

ZHX2 inhibits thyroid cancer metastasis through transcriptional inhibition of S100A14

BackgroundThyroid cancer is the most common malignant endocrine tumour, and metastasis has become the main reason for treatment failure. However, the underlying molecular mechanism of thyroid cancer metastasis remains poorly understood. We investigated the role of the tumour suppressor zinc fingers and homeoboxes 2 (ZHX2) in the metastasis of thyroid cancer.MethodsTo study the role of ZHX2 in thyroid cancer metastasis, we evaluated the EMT process using cell migration, wound healing and lung metastatic tumour formation in vitro and in vivo models.ResultsZHX2 expression was significantly decreased in thyroid cancer tissues, which correlated with poor prognosis of thyroid cancer patients. ZHX2 knockdown significantly promoted the migration of thyroid cancer cells. Mechanistically, ZHX2 associated with the S100 calcium binding protein A14 (S100A14) promoter to decrease the transcription of S100A14. Moreover, S100A14 was highly expressed in human thyroid cancer samples, and its expression negatively correlated with ZHX2 expression.ConclusionsInhibition of S100A14 attenuated the ZHX2 knockdown-induced enhanced metastasis of thyroid cancer cells both in vitro and in vivo. The evidence presented here suggests that ZHX2 inhibits the progression of thyroid cancer by blocking S100A14-mediated metastasis.

Identification of prognostic signature with seven LncRNAs for papillary thyroid carcinoma

PurposeWith the increasing incidence of thyroid cancer (TC), the prognostic risk assessment of thyroid cancer has been becoming more and more important. The aim of this study was to screen TC-related biomarkers and identify key multi-long non coding RNA (lncRNA) signature for prognostic risk assessment of papillary TC. Material and methodsThe lncRNAs differentially expressed between TC tissue and adjacent normal tissue was identified by R language. Bioinformatics analysis was applied to screen the lncRNAs significantly associated with prognosis in TC patients and build the multi-lncRNA signature. The lncRNAs were annotated by co-expression and enrichment analysis to demonstrate the underlying mechanism of their effect on prognosis. Results285 up-regulated and 174 down-regulated differently expressed lncRNAs were identified. Based on seven signature lncRNAs (AL591846.2, AC253536.3, AC004112.1, LINC00900, AC008555.1, TNRC6C-AS1, LINC01736) a prognostic risk assessment model was built. The model can segregate the patients into the high-risk and low-risk groups (P value <0.0001, CI: 0.02∼0.14). ROC analysis revealed that the area under the curve reached 0.86, indicating that this model had an excellent sensitivity and specificity. Also, the model could act as an independent prognostic indication (HR ​= ​2.90, P value ​= ​0.0094 with multivariate analysis). Annotation results further supported and enriched our understanding of the seven signature lncRNAs. Importantly, expression levels of three of the seven lncRNAs were confirmed in Gene Expression Omnibus (GEO) data. ConclusionsThis study has provided a promising method for the prognostic risk assessment in patients with TC.

Clinical Significance of Circulating Tumor Cells (CTCs) and Survivin on Predicting Prognosis in Thyroid Cancer Patients.

Background Clinical significance of circulating tumor cell (CTC) count, mesenchymal CTCs (MCTCs), and survivin in patients with thyroid cancer remains unclear. We evaluated the relationship between the expression of different CTC subtypes or survivin and the prognosis in patients with thyroid cancer. Patients and Methods. This study enrolled 164 patients with thyroid cancer who were diagnosed from January 2013 to September 2020 in our hospital. Among these patients, there were 73 cases with papillary thyroid cancer (PTC), 60 cases with follicular thyroid cancer (FTC), 12 medullary thyroid cancers (MTC), 10 poorly differentiated thyroid cancers (PDTC), 9 anaplastic thyroid cancers, and 10 control patients with nonmalignant thyroid nodules based on their histopathological characteristics. Only 5 milliliters (mL) of peripheral blood from the patients with thyroid cancer and control was used to detect the CTC cell number via CanPatrol capture technique before treatments. We also isolated mononuclear cells (MNC) from the peripheral blood and performed quantity reverse transcriptase polymerase chain reaction (qPCR) for survivin gene expression among these patients. Results The overall positive rates of CTC at diagnosis were 56.1%. The relapse and metastasis rates in PTC and FTC patients with more than 6 CTCs and positive MCTCs were significantly higher than those in the patients with 6 or less than 6 CTCs and MCTCs. It was also found that these patients with >6 CTCs and MCTCs had shorter progression-free survival (PFS). Additionally, the survivin level of the patients with thyroid cancer was strongly relative to differentiation grades of thyroid cancers. Conclusions The detection of more than six of total CTCs and positive MCTCs in the patients with differentiated thyroid cancer is an excellent biomarker for predicting the prognosis of patients. Survivin also is a good biomarker for thyroid cancer differentiation.

CONUT Score: A New Tool for Predicting Prognosis in Patients with Advanced Thyroid Cancer Treated with TKI.

Simple SummaryMany studies have shown that an impaired nutritional status correlated with a worse prognosis in cancer patients. The aim of our retrospective study was to evaluate the potential role of baseline Controlling Nutritional Status (CONUT score) in predicting prognosis of advanced thyroid cancer treated with tyrosine kinase inhibitors (TKI). We were able to confirm that baseline CONUT score significantly correlated with progression free survival (PFS) and overall survival (OS) and was the only independent prognostic factor for both outcomes. In particular, a CONUT score ≥3 was associated with a worse PFS and OS. The CONUT score represents a relatively new screening tool that is useful in predicting prognosis in thyroid cancer patients before the beginning of anti-tumoral treatment.(1) Background: The Controlling Nutritional Status (CONUT) score is an immuno-nutritional screening tool based on serum albumin, total cholesterol, and lymphocyte count. The aim of the study was to assess the CONUT score as a potential prognostic factor of response to therapy in patients with advanced thyroid cancer treated with tyrosine kinase inhibitors (TKIs). (2) Methods: We retrospectively evaluated 42 metastatic thyroid cancer patients (54.8% female). The median age at the time of TKI treatment was 69 years. Histological diagnosis was differentiated thyroid cancer in 66.7%, poorly differentiated thyroid cancer in 21.4%, and medullary thyroid cancer in 11.9% of patients. CONUT score was assessed before starting TKI therapy. (3) Results: Progression-free survival (PFS) and overall survival (OS) were significantly influenced by baseline CONUT score. The best CONUT cut-off able to predict the response to treatment was 3. Both PFS and OS were better in patients with CONUT score <3 than in those with CONUT score ≥3 (p < 0.0001). CONUT score was the only independent prognostic factor associated with PFS (p = 0.021) and OS (p = 0.007). (4) Conclusions: CONUT score represents a relatively new screening tool, easily applicable in clinical practice and potentially useful in predicting prognosis in thyroid cancer patients treated with TKIs.