Marker For Papillary Thyroid Carcinoma Research Articles

Clinicopathological and molecular markers for the identification of Hashimoto’s thyroiditis as a possible predisposing and prognostic factor of papillary thyroid carcinoma

Background: The papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, while Hashimoto’s thyroiditis (HT) is the most common inflam¬matory thyroid disease. The coincidental coexistence or the possible predisposing, protective or aggravating role of HT in the development of PTC have been repeatedly examined. Aim: The aim of the present study was to eval¬uate histopathological and clinical data obtained from pa¬tients with HT, PTC, and PTC+HT so as to investigate the possible association of HT with PTC. Methodology: The study’s cohort consisted of 114 patients (67 PTC, 29 PTC+HT, and 18 HT patients). A full record of their clini¬copathological and clinical laboratory data was followed by extensive statistical analysis in order to reveal possi¬ble correlations between the existence of each disease and various clinicopathological parameters. The study was conducted from 2019 to 2023 at the Hippokration General Hospital of Athens (Greece). Results: A signifi¬cant increase in the levels of thyroid-stimulating hormone (TSH; p=0.031), anti-thyroglobulin antibodies (Anti-Tg; p<0.001), and anti-thyroid peroxidase antibodies (Anti-TPO; p<0.001) was observed in the PTC+HT group. These patients also have smaller tumors (p=0.015) and a younger age of disease onset (p<0.001), while the ma¬jority of PTC+HT patients were women (p=0.023) and had infiltrated lymph nodes (p=0.002). Furthermore, the majority of patients with infiltration of the capsule be¬longed to the PTC+HT group (57.1%; p=0.032). Conclu¬sion: PTC+HT represents a less aggressive clinical state, as good prognostic markers of PTC correlate with the presence of HT. In PTC+HT patients, the PTC tends to have early onset age and the primary tumor is often small, while the majority of PTC+HT patients are women.

Identification of Potential Biomarkers in Papillary Thyroid Carcinoma Based on Proteomics.

To identify biomarkers of papillary thyroid carcinoma (PTC) and explore the possible pathogenic mechanism. This study included five patients with PTC. Protein expression of cancer tissues and adjacent normal thyroid tissues from each patient were analyzed by TMT proteomics technology. Differentially expressed proteins were identified, and functional annotation of differentially expressed proteins was performed by bioinformatics and pathway enrichment analysis. A total of 639 differentially expressed proteins were identified, including 278 upregulated and 361 downregulated proteins. Six upregulated proteins were identified as potential specific markers of PTC. Differentially expressed proteins may represent new molecular markers of PTC. These differentially expressed proteins and the related pathways may provide new insights into the pathogenic mechanisms of PTC.

Estrogen enhances the proliferation, migration, and invasion of papillary thyroid carcinoma via the ERα/KRT19 signaling axis.

Estrogen is thought to be the reason for the higher prevalence of papillary thyroid carcinoma (PTC) in fertile women; however, more study is required to completely comprehend how estrogen affects PTC development at the cellular level. Therefore, we combined Oxford Nanopore Technologies (ONT) sequencing to explore molecular markers of PTC and to investigate the molecular mechanisms by which estrogen promotes PTC development. The expression levels of ESR1 (ERα) and KRT19 in normal thyroid tissues and cancer tissues as well as in different cancer stages, races, genders, age groups, histological subtypes and nodular metastasis status of the TCGA database were analyzed online by Ualcan; the relationship between ESR1, KRT19 and the survival of THCA patients was analyzed. A PTC xenograft tumor model was established. An ERα specific inhibitor (MPP) was administered and an EDU cell proliferation assay was used to verify the effect of estrogen on PTC proliferation. KRT19 was knocked down in KTC-1 cells, and the proliferation, migration, and invasion abilities of PTC cells were determined using CCK-8, immunofluorescence labeling, Western blot for EMT-related proteins, scratch assay, and Transwell assay. The role of ERα in relation to KRT19 was investigated by Western blot and immunofluorescence. The effects of ERα/KRT19 signaling axis on the proliferation, migration and invasion ability of PTC cells were evaluated using EDU cell proliferation assay and Transwell. Using ONT sequencing, 15 pairs of PTC tissue and paracancer tissue samples were collected. A PPI network was constructed to validate the differential expression of KRT19 in combination with biosignature analysis, and the protein interaction between KRT19 and ESR1 was verified using STRING. Ualcan showed that the expression of ESR1 and KRT19 was higher in THCA tissues than in normal thyroid tissues. E2 activation of ERα promoted the growth of PTC cells and tissues. si-KRT19 inhibited the proliferation, migration and invasion of PTC cells. KRT19 together with ERα formed the ERα/KRT19 signaling axis. E2 activation of the ERα/KRT19 signaling axis promoted the proliferation, migration, and invasion of PTC cells. ONT sequencing and STRING website verified that KRT19 is significantly differentially expressed in PTC and that ESR1 and KRT19 have protein interactions and are related to the estrogen signaling pathway. Using public databases, RNA sequencing, and bioinformatics, we discovered that E2 stimulates the ERα/KRT19 signaling axis to stimulate PTC proliferation, migration, and invasion.

FHL1: A novel diagnostic marker for papillary thyroid carcinoma.

Although there are clear morphologic criteria for the diagnosis of papillary thyroid carcinoma (PTC), when the morphology is untypical or overlaps, accurate diagnostic indicators are necessary. Since few studies investigated the role of down-regulated genes in PTC, this article aims to further explore the molecular markers associated with PTC. We conducted bioinformatics analysis of gene microarrays of PTC and normal adjacent tissues. Besides, quantitative real-time quantitative polymerase chain reaction array and immunohistochemical staining were used to investigate the expression of the major down-regulated genes. The results indicated that several important down-regulated genes, including TLE1, BCL2, FHL1, GHR, KIT, and PPARGC1A were involved in the process of PTC. Compared to normal adjacent tissues, the mRNA expression of the major genes was down-regulated in PTC (p＜0.05). Immunohistochemically, FHL1 shows negative or low expression in PTC tissues (p＜0.05). BCL2 did not show a significant difference between PTC and normal thyroid tissues (p > 0.05). TLE1, KIT, PPARGC1A and GHR showed negative expression in both tumor and normal tissues. These results suggested that FHL1 could serve as a novel tumor marker for precise diagnosis of PTC.

Proteomic and Phosphoproteomic analysis of thyroid papillary carcinoma: Identification of potential biomarkers for metastasis

Thyroid cancer has emerged as the most rapidly proliferating solid neoplasm. In this study, we included a cohort of patients who underwent sonographic assessment and surgical intervention at the Sir Run Run Shaw Hospital, associated with the School of Medicine at Zhejiang University, spanning from January 2019 to June 2020. Stratification of cases was based on a combination of preoperative ultrasonographic evaluations and postoperative histopathological diagnoses, resulting in three distinct groups: high-risk papillary thyroid carcinoma (PTC) labeled as C1, low-risk PTC designated as C2, and a control group (N) composed of benign thyroid tissue adjacent to the carcinoma. Proteomic and phosphoproteomic analyses were conducted on PTC specimens. The comparative assessment revealed that proteins up-regulated in the C1/N and C2/N groups were predominantly involved in functions such as amino acid binding, binding of phosphorylated compounds, and serine protease activity. Notably, proteins like NADH dehydrogenase, ATP synthase, oxidoreductases, and iron ion channels were significantly elevated in the C1 versus C2 comparative group. Through meticulous analysis of differential expression multiples, statistical significance, and involvement in metabolic pathways, this study identified eight potential biomarkers pertinent to PTC metastasis diagnostics, encompassing phosphorylated myosin 10, phosphorylated proline-directed protein kinase, leucine tRNA synthetase, 2-oxo-isovalerate dehydrogenase, succinic semialdehyde dehydrogenase, ADP/ATPtranslocase, pyruvate carboxylase, and fibrinogen. Therapeutic assays employing metformin, an AMP-activated protein kinase (AMPK) activator, alongside the phosphorylation-specific inhibitor ML-7 targeting Myosin10, demonstrated attenuated cellular proliferation, migration, and invasion capabilities in thyroid cancer cells, accompanied by a reduction in amino acid pools. Cellular colocalization and interaction studies elucidated that AMPK activation imposes an inhibitory influence on Myosin10 levels. The findings of this research corroborate the utility of proteomic and phosphoproteomic platforms in the identification of metastatic markers for PTC and suggest that modulation of AMPK activity, coupled with the inhibition of Myosin10 phosphorylation, may forge novel therapeutic avenues in the management of thyroid carcinoma. SignificanceThe significance of our research lies in its potential to transform the current understanding and management of thyroid papillary carcinoma (PTC), particularly in its metastatic form. By integrating both proteomic and phosphoproteomic analyses, our study not only sheds light on the molecular alterations associated with PTC but also identifies eight novel biomarkers that could serve as indicators of metastatic potential.

Availability of Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) as a Surrogate Tumor Marker for Papillary Thyroid Carcinoma.

Thyroglobulin (Tg) is a very sensitive and specific marker in patients who have undergone total thyroidectomy for papillary thyroid carcinoma (PTC). However, the presence of a Tg antibody (TgAb) interferes with Tg immunometric assays, making Tg levels unreliable indicators. There are currently no other tumor markers to monitor in patients with PTC whose serum is TgAb-positive. Thus, we investigated whether carbohydrate antigen 19-9 (CA19-9) can be used as a tumor marker for PTC. We retrospectively analyzed 196 consecutive patients with PTC (maximum diameter ≥ 2 cm). The serum CA19-9 and Tg values of each patient were obtained before and 0.5-1 month postsurgery. Immunohistochemical staining for PTC was performed using an antibody against CA19-9. High pre-surgery serum levels of CA19-9 were observed in 6.1% of the patients. Postsurgery, serum CA19-9 levels in all 196 patients decreased considerably and were within the normal range. CA19-9 expression was detected in 28 of 62 PTCs (45.2%) and was detected at various degrees and ranges in conventional PTC histology. Although further studies with longer follow-ups are necessary, serum CA19-9 levels may serve as a surrogate tumor marker for PTC in place of serum Tg levels sin some patients.

Machine-learning-based prediction of a diagnostic model using autophagy-related genes based on RNA sequencing for patients with papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer and belongs to the category of malignant tumors of the thyroid gland. Autophagy plays an important role in PTC. The purpose of this study is to develop a novel diagnostic model using autophagy-related genes (ARGs) in patients. In this study, RNA sequencing data of PTC samples and normal samples were obtained from GSE33630 and GSE29265. Then, we analyzed GSE33630 datasets and identified 127 DE-ARGs. Functional enrichment analysis suggested that 127 DE-ARGs were mainly enriched in pathways in cancer, protein processing in endoplasmic reticulum, toll-like receptor pathway, MAPK pathway, apoptosis, neurotrophin signaling pathway, and regulation of autophagy. Subsequently, CALCOCO2, DAPK1, and RAC1 among the 127 DE-ARGs were identified as diagnostic genes by support vector machine recursive feature elimination and least absolute shrinkage and selection operator algorithms. Then, we developed a novel diagnostic model using CALCOCO2, DAPK1, and RAC1 and its diagnostic value was confirmed in GSE29265 and our cohorts. Importantly, CALCOCO2 may be a critical regulator involved in immune microenvironment because its expression was related to many types of immune cells. Overall, we developed a novel diagnostic model using CALCOCO2, DAPK1, and RAC1 which can be used as diagnostic markers of PTC.

LncRNA PFAR facilitates the proliferation and migration of papillary thyroid carcinoma by competitively binding to miR-15a

Papillary thyroid carcinoma (PTC) is type of aggressive tumor, with a markedly declined survival rate when distant metastasis occurs. It is of great significance to develop potential biomarkers to evaluate the progression of PTC. LncRNAs are recently widely claimed with biomarker value in malignant tumors. Herein, the role of LncRNA PFAR in PTC was investigated to explore potential prognostic marker for PTC. Compared to NTHY-ORI 3-1 cells, LncRNA PFAR was found markedly upregulated in PTC cell lines. In LncRNA PFAR knockdown TPC-1 cells, markedly declined cell viability, increased apoptotic rate, enhancive number of migrated cells, and elevated migration distance were observed, accompanied by a suppressed activity of the RET/AKT/mTOR signaling. In LncRNA PFAR overexpressed BCPAP cells, signally increased cell viability, declined apoptotic rate, reduced number of migrated cells, decreased migration distance, and increased tumor volume and tumor weight in nude mice xenograft model were observed, accompanied by an activation of the RET/AKT/mTOR signaling. The binding site between LncRNA PFAR and miR-15a, as well as miR-15a and RET, was confirmed by the dual luciferase reporter assay. The FISH study revealed that LncRNA PFAR was mainly located in the cytoplasm. Furthermore, the impact of the siRNA targeting LncRNA PFAR against the growth and migration of PTC cells was abolished by the inhibitor of miR-15a or SC79, an activator of AKT/mTOR signaling. Collectively, LncRNA PFAR facilitated the proliferation and migration of PTC cells by mediating the miR-15a/RET axis.

Clinical significance and diagnostic value of QPCT, SCEL and TNFRSF12A in papillary thyroid cancer.

To identify specific novel genes that could be used as diagnostic and prognostic factors in papillary thyroid carcinoma (PTC). Screening of differential genes by RNA sequencing (RNA-Seq) in normal thyroid, Hashimoto's thyroiditis, PTC combined with Hashimoto's thyroiditis and PTC tissues. The genes QPCT, SCEL and TNFRSF12A were selected by qRT-PCR and immunohistochemical pre-experiments. The GEPIA2 database, qRT-PCR, and immunohistochemical studies were used to confirm the target genes QPCT, SCEL, and TNFRSF12A. ROC curves were used to assess the diagnostic usefulness of these 3 genes for PTC in more detail. Functional enrichment analysis showed that QPCT, SCEL and TNFRSF12A were enriched in the pathways for peptidyl-pyroglutamic acid biosynthesis, keratinocyte differentiation, WNT signaling, apoptosis. GEPIA2 database analysis revealed that QPCT, SCEL and TNFRSF12A were high in thyroid cancer, and TC patients with lower TNFRSF12A levels had short survival. QPCT, SCEL and TNFRSF12A were elevated in PTC and thyroid adenoma. The mRNA diagnostic values were as follows: for QPCT, AUROC =0.891, 95% CI, 0.835-0.947; for SCEL, AUROC =0.921, 95% CI, 0.869-0.974; for TNFRSF12A, AUROC =0.884, 95% CI, 0.809-0.958. Immunohistochemical results showed that QPCT, SCEL, and TNFRSF12A differed to varying degrees between subgroups of thyroid tissue. SCEL was associated with BRAF V600E mutation status and stratification of recurrence risk, while TNFRSF12A was associated with Cyclin D1. The protein diagnostic values were as follows: for QPCT, AUROC =0.752, 95% CI, 0.685-0.819; for SCEL, AUROC =0.715, 95% CI, 0.645-0.784; for TNFRSF12A, AUROC =0.660, 95% CI, 0.587-0.734. QPCT, SCEL and TNFRSF12A are expected to be diagnostic markers for PTC.

NT5E DNA methylation in papillary thyroid cancer: Novel opportunities for precision oncology

The ectoenzyme CD73, encoded by the NT5E gene, has emerged as a potential prognostic and therapeutic marker for papillary thyroid carcinoma (PTC), which has increased in incidence in recent decades. Here, from The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA) database, we extracted and combined clinical features, levels of NT5E mRNA, and DNA methylation of PTC samples and performed multivariate and random forest analyses to evaluate the prognostic relevance and the potential of discriminating between adjacent non-malignant and thyroid tumor samples. As a result, we revealed that lower levels of methylation at the cg23172664 site were independently associated with BRAF-like phenotype (p = 0.002), age over 55 years (p = 0.012), presence of capsule invasion (p = 0.007) and presence of positive lymph node metastasis (LNM) (p = 0.04). The methylation levels of cg27297263 and cg23172664 sites showed significant and inversely correlations with levels of NT5E mRNA expression (r = −0.528 and r = −0.660, respectively), and their combination was able to discriminate between adjacent non-malignant and tumor samples with a precision of 96%–97% and 84%–85%, respectively. These data suggest that combining cg23172664 and cg27297263 sites may bring new insights to reveal new subsets of patients with papillary thyroid carcinoma.

Cell-free DNA methylation biomarker for the diagnosis of papillary thyroid carcinoma.

Cell-free DNA (cfDNA) is being explored as biomarker for non-invasive diagnosis of cancer. We aimed to establish a cfDNA-based DNA methylation marker panel to differentially diagnose papillary thyroid carcinoma (PTC) from benign thyroid nodule (BTN). 220 PTC- and 188 BTN patients were enrolled. Methylation markers of PTC were identified from patients' tissue and plasma by reduced representation bisulfite sequencing and methylation haplotype analyses. They were combined with PTC markers from literatures and were tested on additional PTC and BTN samples to verify PTC-detecting ability using targeted methylation sequencing. Top markers were developed into ThyMet and were tested in 113 PTC and 88 BTN cases to train and validate a PTC-plasma classifier. Integration of ThyMet and thyroid ultrasonography was explored to improve accuracy. From 859 potential PTC plasma-discriminating markers that include 81 markers identified by us, the top 98 most PTC plasma-discriminating markers were selected for ThyMet. A 6-marker ThyMet classifier for PTC plasma was trained. In validation it achieved an Area Under the Curve (AUC) of 0.828, similar to thyroid ultrasonography (0.833) but at higher specificity (0.722 and 0.625 for ThyMet and ultrasonography, respectively). A combinatorial classifier by them, ThyMet-US, improved AUC to 0.923 (sensitivity=0.957, specificity=0.708). The ThyMet classifier improved the specificity of differentiating PTC from BTN over ultrasonography. The combinatorial ThyMet-US classifier may be effective in preoperative diagnosis of PTC. This work was supported by the grants from National Natural Science Foundation of China (82072956 and 81772850).

Development and validation of the nomogram based on ultrasound, thyroid stimulating hormone, and inflammatory marker in papillary thyroid carcinoma: a case-control study.

The increase in the number of thyroid cancer cases in recent years has increased not only the medical burden but also the potential for overtreatment. Therefore, it is crucial to distinguish papillary thyroid cancer from benign thyroid nodules before surgery when treating thyroid nodules. The patients were divided into two groups: 117 patients made up the validation cohort and 414 patients made up the primary cohort. As a result of the primary cohort, a preoperative prediction model was developed, which was then validated externally in the validation cohort. Preoperative thyrotropin (thyroid stimulating hormone, TSH), systemic immune-inflammation index (SII), lymphocyte-to-monocyte ratio (LMR), and ultrasonographic features were recorded in both groups. As predictors for the model, the preoperative blood levels of TSH, SII, LMR, echogenicity, margin, calcification, composition, taller-than-wide, and age were chosen. This was the regression equation: Y = -0.070 × (age) + 1.511 × (echogenicity) + 1.664 × (margin) + 1.003 × (calcification) + 0.939 × (composition) + 2.964 × (tall than wide) + 0.305 × (TSH) + 0.558 × (SII) - 1.271 × (LMR) + 0.327. Papillary thyroid carcinoma (PTC) was predicted positively with values of Y ≥0.808. The prediction model's accuracy, sensitivity, and specificity were 88.2%, 85.1%, and 94.9%, respectively. The area under the receiver operating characteristic (ROC) curve was 0.961. The model's external validation produced satisfactory results with accuracy, sensitivity, and specificity of 85.5%, 90.9%, and 75.5%, respectively. Using the preoperative TSH, SII, LMR, and ultrasonographic characteristics, a straightforward and accurate preoperative prediction model for PTC has been developed and validated. The preoperative assessment of PTC in clinical application is enhanced by this approach.

Lymph node metastasis‐dependent molecular classification in papillary thyroid carcinoma defines aggressive metastatic outgrowth

Lymph node metastasis‐dependent molecular classification in papillary thyroid carcinoma defines aggressive metastatic outgrowth

Expanding the Spectrum of BRAF Non-V600E Mutations in Thyroid Nodules: Evidence-Based Data from a Tertiary Referral Centre.

The BRAF p.V600E mutation represents the most specific marker for papillary thyroid carcinoma and is potentially related to aggressive behavior and persistent disease. BRAF alterations other than the p.V600E are less common in thyroid carcinoma and represent an alternative mechanism of BRAF activation with unclear clinical significance. The study aims to describe the frequency and clinicopathologic characteristics of BRAF non-V600E mutations in a large cohort (1654 samples) of thyroid lesions characterized by next-generation sequencing. BRAF mutations have been found in 20.3% (337/1654) of thyroid nodules, including classic (p.V600E) mutation in 19.2% (317/1654) of samples and non-V600E variants in 1.1% of cases (19/1654). BRAF non-V600E alterations include 5 cases harboring p.K601E, 2 harboring p.V600K substitutions, 2 with a p.K601G variant, and 10 cases with other BRAF non-V600E alterations. BRAF non-V600E mutations have been reported in one case of follicular adenoma, three cases of conventional papillary thyroid carcinoma, eight cases of follicular variant of papillary carcinomas, one case of columnar cell variant papillary thyroid carcinoma, one case of oncocytic follicular carcinoma, and two bone metastasis of follicular thyroid carcinoma. We confirm that BRAF non-V600E mutations are uncommon and typically found in indolent follicular-patterned tumors. Indeed, we show that BRAF non-V600E mutations can be found in tumors with metastatic potential. However, in both aggressive cases, the BRAF mutations were concomitant with other molecular alterations, such as TERT promoter mutation.

Cancer-associated fibroblasts in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) has a relatively good prognosis, yet there are some invasive PTC cases with worse clinicopathological features and poor outcome. Cancer-associated fibroblasts (CAFs) play an important role in cancer invasion and metastasis. This study aimed to investigate the expression of marker proteins of CAFs in PTC and their correlations with clinicopathological features through immunohistochemistry. The medical records of 125 PTC patients were reviewed in this study, whose specimens were retrieved for immunohistochemistry. Four CAFs marker proteins, FAP fibroblast activated protein (FAP), α-smooth muscle actin (α-SMA), Vimentin and platelet-derived growth factor receptor-α(PDGFR-α), were stained and scored. Then, statistical analyses were performed. The immunoreactivity scores of FAP and α-SMA correlated with tumor size, BRAF mutation, extrathyroidal, invasion, pathological subtype, lymph node metastasis and ATA risk stratification. Moreover, binary logistic regression analysis and receiver operating characteristic curves showed that high FAP and α-SMA immunoreactivity scores were risk factors for extrathyroidal invasion, BRAF mutation, multi-focality and lymph node metastasis (especially N1b) with good sensitivity and accuracy in prediction. A better performance was found in FAP than α-SMA. Strong expressions of CAFs were risk factors for worse thyroid cancer clinicopathological features. FAP was the better CAFs marker for PTC.

Can anti-thyroglobulin antibody (anti-Tg) be a tumor marker for recurrence in papillary thyroid carcinoma (PTC) in patients without autoimmune thyroiditis (AIT)?: A case report

Abstract Introduction Thyroid carcinoma is the most common malignancy of the endocrine system, accounting for 1% of all newly diagnosed cancers. Thyroglobulin (Tg) is a tumor marker for papillary thyroid carcinoma (PTC) if the anti-thyroglobulin antibody (anti-Tg) is negative. In autoimmune thyroiditis (AIT) patients with positive anti-Tg, the level of this antibody can be a marker in the follow-up of PTC, since the anti-Tg concentration depends on the amount of Tg-secreting tissue. However, there is no clear data on whether the development of anti-Tg positivity during follow-up is an indicator of recurrence in a patient who has neither AIT nor anti-Tg positivity before surgery. Clinical Case 21-year-old male admitted to our hospital with a complaint of a palpable mass on the neck. The patient was euthyroid and thyroid autoantibodies were negative. In neck ultrasonography (US), 10 mm EU-TIRADS 5 nodule in right lobe and pathologic lymphs nodes in right cervical compartments were detected, and FNABs were done. Results were consistent with PTC. Total thyroidectomy, central and right neck dissection were performed. Histopathology report resulted in classic variant 2 cm PTC in right lobe, one central and 10 lateral pathologic lymph nodes among a total of 41. While 150 mCi RAI was given as adjuvant therapy; TSH level was 109 µIU/ml, Tg was 11 ng/mL and anti-Tg was negative. No involvement was detected in the post-RAI whole body scan except microscopic residual RAI avid foci in the thyroid bed and upper mediastinum. No pathologic focus was observed in the upper mediastinum in thorax CT. During one year, he was followed with an excellent response. At the end of the first year after surgery, anti-Tg antibody was detected as positive with 6.63 IU/mL (0–4 normal range) when neck ultrasonography and thyroglobulin were negative (<0.1 ng/mL). At the end of the second year that the patient was under close follow-up, the anti-Tg titer increased to 8 IU/mL and neck US revealed a single suspicious 7×6mm, round lymph node, with loss of normal hilum, in the central compartment (level VI-VII). Central lymph node dissection was performed when Tg washout was positive in this lymph node. Histopathological examination resulted in two metastatic (2 and 3 mm) lymph nodes out of four lymph nodes removed. In postoperative third months, Tg and anti-Tg were negative. Conclusion This case shows that anti-Tg can be used as a tumor marker for PTC in patients without AIT. It was thought that the autoimmunity that developed afterwards against the thyroglobulin antigen might have been triggered by the thyroglobulin that passed into the serum after the adjuvant rai treatment, and it might have turned into a tumor marker in this way for this patient. Therefore, we recommend that anti-Tg testing should be continued in the follow-up of patients with PTC whose anti-Tg were not positive before surgery.

Identification of potential biomarkers for papillary thyroid carcinoma by comprehensive bioinformatics analysis.

To perform bioinformatics analysis on the papillary thyroid carcinoma (PTC) gene chip dataset to explore new biological markers for PTC. The gene expression profiles of GSE3467 and GSE6004 chip data were collected by GEO2R, and the differentially expressed genes (DEGs) were selected for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Protein-protein interaction (PPI) relationship analysis was achieved using STRING, and the hub genes were obtained using the Cytoscape software. GEPIA was used to validate the expressions of the hub genes in the normal and tumor tissues and to conduct survival analyses. Pertinent genetic pathology results were fetched using the HPA database. Finally, the key genes were clinically verified by reverse transcription-polymerase chain reaction. 97 genes were jointly up-regulated and 107 genes were jointly down-regulated in GSE3467 and GSE6004. GO function enrichment analysis revealed that the DEGs were involved in the regulation of calcium ion transport into cytosol, integrin binding, and cell adhesion molecule binding. KEGG pathway enrichment analysis indicated that the DEGs were chiefly associated with thyroid cancer and non-small cell lung cancer. According to the PPI network, 30 key target genes were identified. Only the expressions of ANK2, TLE1, and TCF4 matched between the normal and tumor tissues, and were associated with disease prognosis. When compared with the normal thyroid tissues, the protein and mRNA expressions of ANK2, TLE1, and TCF4 were down-regulated in PTC. Significant differences exist in overall gene expression between the thyroid tissues of patients with PTC and those of healthy people. Furthermore, the differential genes ANK2, TLE1, and TCF4 are expected to be reliable molecular markers for the mechanism study and diagnosis of PTC.

The Value of Ki-67 Labeling Index in Central Lymph Node Metastasis and Survival of Papillary Thyroid Carcinoma: Evidence From the Clinical and Molecular Analyses.

Recent evidence suggests that the Ki-67 labeling index is associated with lymph node metastasis and the prognosis of papillary thyroid carcinoma (PTC). We retrospectively evaluated the clinicopathological features of consecutive PTC patients between Jan 2019 and Oct 2020 in our medical center. The molecular analysis was also conducted by using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) program. The Chi-square test was performed for the comparison of variables between patients with central lymph node metastasis (CLNM) and not. Besides, univariate and stepwise multivariate logistic regression analyses were further used to determine the risk factors for CLNM in PTC. Our results showed that male gender (odd ratio (OR) = 3.02; 95% CI: 1.81-5.04), tumor size >1cm (OR = 2.81; 95% CI: 1.84-4.29), multifocality (OR = 2.08; 95% CI: 1.31-3.30, and Ki-67 labeling index (>3% and ≤5%: OR = 1.20; 95% CI: .73-1.97; >5%: OR = 3.85; 95% CI: 1.62-9.14) were independent risk factors for CLNM. After excluding the patients with harvested central lymph nodes <3, increased Ki-67 labeling index was still associated with the number of CLNM and the lymph node ratio. Additionally, the expression level of Ki-67 was significantly correlated with a higher N stage and worse disease-free survival in TCGA and validated GSE60542 datasets. Higher Ki-67 labeling index (>5%) is significantly associated with the CLNM in PTC patients, like other indicators of the male gender, larger tumor size, and multifocality. Besides, the Ki-67 was also determined to be associated with CLNM and DFS in PTC patients, which may act as an important molecular marker in PTC.

Preoperative Diagnostics of Papillary Thyroid Carcinoma by Molecular Analysis of FNAB Materials

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Molecular markers of papillary thyroid carcinoma (PTC) including the BRAFT1799A mutation, RET/PTC1,3 rearrangements, and differentially expressed SFTPB (up-regulated) and TFF3 (down-regulated) genes were prospectively assessed in FNAB (fine needle aspiration biopsy) material from thyroid nodules. We examined 73 cases, of them 59 PTC (papillary thyroid carcinoma), five nodular goiters, and nine follicular adenomas. Concordantly with cytology, molecular diagnosis of PTC by SFTPB and TFF3 expression levels was confirmed in 38/41 cases (92.7%); in them, 22/41 (53.6%) had BRAFT1799A mutation and 7/41 (17.1%) had RET/PTC rearrangements. For benign nodules, concordance was observed in 10/12 (83.3%) cases. Among 20 cases, including 19 suspicious for malignancy and one inadequate sample, 17 were positive for SFTPB/TFF3 test (85.0%). Of these, four were also positive for RET/PTC rearrangements, five were positive for BRAFT1799A and all resulted in PTC at histology. The remaining 3 cases were negative for three molecular markers. These nodules showed benign lesions in histology. Our results demonstrated that specific molecular tests improve the efficacy of preoperative diagnostics of PTC.

EVALUATION OF INFLAMMATION-RELATED HEMOGRAM PARAMETERS AS A USEFUL MARKER IN PAPILLARY THYROID CARCINOMA

Objective&#x0D; Inflammation-related hemogram parameters have&#x0D; recently started to be defined as a useful marker in&#x0D; cancer patients. In this study, we aimed to comparison&#x0D; of hemogram parameters in papillary thyroid cancer&#x0D; (PTC) patients, well differentiated thyroid tumor&#x0D; of uncertain malignant potential (WDT-UMP) and&#x0D; follicular adenoma (FA).&#x0D; Material and Method&#x0D; The 287 patients’ data were analyzed in study. Study&#x0D; subjects were divided into 5 different groups. 1st&#x0D; group: control, 2nd group: FA, 3rd group: WDT-UMP,&#x0D; 4th group: non-metastatic PTC, 5th group: metastatic&#x0D; PTC. We evaluated the preoperative blood tests.&#x0D; Results&#x0D; The average age was 50 (37-59). The mean TSH&#x0D; value was 1.2 (0.5-2.2) μIU/mL. The mean size of the&#x0D; lesion detected in the total thyroidectomy material was&#x0D; 1.7 (1.0-3.0) cm. White blood cells (WBC), neutrophils&#x0D; and lymphocytes were lower in 3rd group than 4th&#x0D; group (p