Identification of a four-miRNA signature predicts the prognosis of papillary thyroid cancer

BACKGROUND In recently diagnosed patients with thyroid cancer,papillary thyroid cancer(PTC),as the most common histological subtype,accounts for 90%of all cases.Although PTC is known as a relatively adolescent malignant disease,there still is a high possibility of recurrence in PTC patients with a poor prognosis.Therefore,new biomarkers are necessary to guide more effective stratification of PTC patients and personalize therapy to avoid overtreatment or inadequate treatment.Accumulating evidence demonstrates that microRNAs(miRNAs)have broad application prospects as diagnostic biomarkers in cancer.AIM To explore novel markers consisting of miRNA-associated signatures for PTC prognostication.METHODS We obtained and analyzed the data of 497 PTC patients from The Cancer Genome Atlas.The patients were randomly assigned to either a training or testing cohort.RESULTS We discovered 237 differentially expressed miRNAs in tumorous thyroid tissues compared with normal tissues,which contained 172 up-regulated and 65 downregulated miRNAs.The evaluation of differently expressed miRNAs was conducted using our risk score model.We then successfully generated a fourmiRNA potential prognostic signature[risk score=(-0.001×hsa-miR-181a-2-3p)+(0.003×hsa-miR-138-5p)+(-0.018×hsa-miR-424-3p)+(0.284×hsa-miR-612)],which reliably distinguished patients from high and low risk with a significant difference in the overall survival(P<0.01)and was effective in predicting the five-year disease survival rate with the area under the receiver operating characteristic curve of 0.937 and 0.812 in the training and testing cohorts,respectively.Additionally,there was a trend indicated that high-risk patients had shorter relapse-free survival,although statistical significance was not reached(P=0.082)in our sequencing cohort.CONCLUSION Our results indicated a four-miRNA signature that has a robust predictive effect on the prognosis of PTC.Accordingly,we would recommend more radical therapy and closer follow-ups for highrisk groups.

Efficacy of anlotinib combined with radioiodine to treat scalp metastasis of papillary thyroid cancer:A case report and review of literature

BACKGROUND Papillary thyroid cancer(PTC)is one of the well-differentiated thyroid tumors.Cutaneous metastasis from differentiated thyroid cancers occurs in<1%of primary thyroid carcinomas but produces the worst survival prognosis.The multi-targeting tyrosine kinase inhibitor anlotinib has been approved to treat refractory advanced non-small-cell lung cancer as well as advanced soft-tissue and clear cell sarcomas in China.CASE SUMMARY In a patient with scalp metastasis caused by PTC,thyroid and skull metastasis tumor sizes were significantly reduced after a trial of neoadjuvant anlotinib therapy for 3 cycles.Anlotinib maintenance medication after thyroidectomy further reduced the metastatic skull tumor size thereby preventing the requirement for craniotomy.CONCLUSION The outcome of the present trial confirmed the potential of anlotinib therapy to treat scalp metastasis induced by PTC and point the way for the treatment of similar diseases in the future.

Intratumoral Bacteria Dysbiosis Is Associated with Human Papillary Thyroid Cancer and Correlated with Oncogenic Signaling Pathways

Emerging evidence suggests that microbial dysbiosis plays vital roles in many human cancers.However,knowledge of whether the microbial community in thyroid tumor is related to tumorigenesis remains elusive.In this study,we aimed to explore the microbial community in thyroid tissues and its contribution to papillary thyroid cancer(PTC).In parallel,we performed microbial profiling and transcriptome sequencing in the tumor and adjacent normal tissues of a large cohort of 340 PTC and benign thyroid nodule(BTN)patients.Distinct microbial signatures were identified in PTC,BTN,and their adjacent nontumor tissues.Intra-thyroid tissue bacteria were verified by means of bacteria staining,fluorescence in situ hybridization,and immunoelectron microscopy.We found that 17 bacterial taxa were differentially abundant in PTC compared with BTN,which included enrichment in PTC of the pathobionts Rhodococcus,Neisseria,Streptococcus,Halomonas,and Devosia,and depletion of the beneficial bacteria Amycolatopsis.These differentially abundant bacteria could differentiate PTC tumor tissues(PTC-T)from BTN tissues(BTN-T)with an area under the curve(AUC)of 81.66%.Microbial network analysis showed increased correlation strengths among the bacterial taxa in PTC-T in comparison with BTN-T.Immunefunction-corresponding bacteria(i.e.,Erwinia,Bacillus,and Acinetobacter)were found to be enriched in PTC with Hashimoto’s thyroiditis.Moreover,our integrative analysis revealed that the PTC-enriched bacteria had a positive association with key PTC-oncogenic pathway-related genes,including BRAF,KRAS,IRAK4,CTNNB1,PIK3CA,MAP3K7,and EGFR.In conclusion,our results suggest that intratumor bacteria dysbiosis is associated with the thyroid tumorigenesis and oncogenic signaling pathways of PTC.

Multifocal papillary thyroid cancer in Graves’ disease: A case report

BACKGROUND Thyroid cancer is not commonly observed in patients with Graves’disease(GD).The presence of thyroid nodules in GD is not uncommon.However,a link bet-ween these two entities has been reported.Herein,we report the case of a patient with GD and thyroid cancer in Saudi Arabia,which has not been reported previously in our region.CASE SUMMARY A 26-year-old male patient with GD,receiving carbimazole for 2 years,presented to our hospital.His hyperthyroidism was controlled clinically and biochemically.On clinical examination,he was found to have a left-sided thyroid nodule.Ultra-sound revealed a 2.6 cm hypoechoic nodule with high vascularity.He was then referred for fine needle aspiration which showed that the nodule was highly suspicious for malignancy.The patient underwent total thyroidectomy and was diagnosed with multifocal classical micropapillary thyroid cancer.Post thyroid-ectomy he received radioactive iodine ablation along with levothyroxine replace-ment therapy.CONCLUSION Careful preoperative assessment and thyroid gland ultrasound might assist in screening and diagnosing thyroid cancer in patients with GD.

Relationship between Whole Body Iodine-131 Effective Half-Life and Estimated Glomerular Filtration Rate for Papillary Thyroid Cancer Patients Undergoing Radioactive Iodine Therapy

Background: The aim of this work was to examine the relationship between the estimated glomerular filtration rate (eGFR) as indicator of renal efficiency potentially related to the ability to release radioactive iodine from the patients bodies and the radioactive iodine whole body effective half-life (WBEHL) defined as the time taken for the administered activity to decay to half of its value for papillary thyroid cancer (PTC) patients undergoing radioactive iodine therapy (RAIT) in a tertiary care medical Centre. Methods: This retrospective observational study included seventy nine patients, sixty females and nineteen males. The patients were divided in two subgroups, those who have WBEHL of less than 11 hours (n = 51) and those with more than 11 (n = 28) hrs based on k-means clustering technique. Results: Analysis of variance (ANOVA) was used to find out if there is a statistically significant difference between the two subgroups Conclusion: There was not a statistically significant difference between the short and the longer WBEHL patients’ groups analyzed in this study. .

Relationship between Expression of Vascular Endothelial Growth Factor and Cervical Lymph Node Metastasis in Papillary Thyroid Cancer: A Meta-analysis

The aim of the present study was to examine the relationship between the protein expression of vascular endothelial growth factor（VEGF） and lymph node metastasis（LNM） in papillary thyroid cancer（PTC）. VEGF-related articles that had been published until August 2016 were searched from the Pub Med, EMBASE, and MEDLINE to identify the risk factors of LNM in PTC. Rev Man 5.3 software was used for the meta-analysis. Finally, 9 articles met the inclusion criteria and were included in our meta-analysis. LNM was found to be present in 176 of 318 patients（57.8%） with high VEGF expression and in 71 of 159 patients（47.0%） with low VEGF expression. The overall OR was 2.81（95% confidence interval, 1.49–5.29）. LNM occurred more frequently in patients with high VEGF expression than in those with low VEGF expression（P=0.001）. Heterogeneity was markedly decreased in the subgroup analyses of LNM in terms of the patients＇ country of origin and the detection methods. Our meta-analysis concluded that the VEGF protein expression is associated with LNM in PTC.

Ultrasound features of extranodal extension in the metastatic cervical lymph nodes of papillary thyroid cancer:a case-control study

Objective：Extranodal extension in cervical lymph nodes is an important risk factor for the progression and prognosis of papillary thyroid cancer.The purpose of this study was to identify the common and characteristic preoperative ultrasonography features that are associated with the pathologic extranodal extension of metastatic papillary thyroid carcinoma.Methods：We retrospectively assessed and compared clinicopathologic and ultrasound features between 60 papillary thyroid cancer patients with extranodal extension and 120 control patients with papillary thyroid cancer without extranodal extension.Results：With respect to the pathological N stage and clinicopathologic features,N1b stage papillary thyroid carcinomas were more frequently found in patients who were extranodal extension-positive,in comparison with those who were extranodal extension-negative（78.3%vs.63.3%,P=0.043）.Extranodal extension was detected most frequently in level VI cervical lymph nodes（48.7%）.In our univariate analysis of patients with papillary thyroid carcinoma,cervical lymph nodes with extranodal extension showed higher incidences of node matting,microcalcification,cystic area,aspect ratio＆lt;2,and larger diameter than those without extranodal extension（all P〈0.05）.Our multivariate analysis demonstrated that node matting and cystic area were independent risk factors for the presence of extranodal extension[odds ratio（OR）：4.751,95%confidence interval（CI）：1.212~18.626,P=0.025;OR：2.707,95%CI：1.127~6.502,P=0.026].Conclusions：Common ultrasound features may indicate the presence of extranodal extension in patients with metastatic cervical lymph nodes of papillary thyroid carcinoma.

Late recurrence of papillary thyroid cancer from needle tract implantation after core needle biopsy: A case report

BACKGROUND Papillary thyroid cancer(PTC)has good prognosis so that the local recurrence or distant metastasis can occur later on the lifetime follow up.In this study,we report recurrence of PTC in subcutaneous area combined with lymph node metastasis.A suspicion of needle tract implantation after core needle biopsy was found.CASE SUMMARY A 66-year-old female patients who underwent right thyroid lobectomy for PTC complained of palpable nodule on anterior neck area.The location of the palpable nodule was not associated with her postoperative scar.After excision of the skin tumor,it was diagnosed as recurrence of PTC.Furthermore,results of subsequent imaging showed lymph node metastasis on her right cervical area.According to the previous medical records,the patient received core needle biopsy through the neck of the patient midline and hematoma was noted after the procedure.The time interval from the first diagnosis to local recurrence or metastasis to the skin and lymph nodes was ten years.As treatment,the patient underwent lymph node dissection in the right and completion thyroidectomy for radioisotope treatment.CONCLUSION Needle tract implantation can occur after core needle biopsy.Further studies are needed to compare core-needle biopsy and fine-needle aspiration.

Mechanism of SCD1 in promoting proliferation,migration and invasion of human papillary thyroid cancer cells

Objective:To investigate the effects of SCD1 on the proliferation,migration and invasion of human papillary thyroid cancer cell line TPC1.Methods:The expression of SCD1 in human thyroid follicular epithelial normal cells Nthy-ori 3-1 and thyroid papillary carcer cell lines TPC1,BCPAP and K1 was detected by Western blot.The negative control and SCD1 siRNA were transfected respectively into human thyroid papillary carcer cell line TPC1,then the expressions of SCD1 mRNA and protein in each group were tested by real-time fluorescence quantitative PCR(qRT-PCR)and Western blot.The effects of interfering SCD1 on the proliferation,migration and invasion of TPC1 cells were detected by CCK-8 method and Transwell chamber assay respectively.Meanwhile,the expression levels of epithelial-mesenchymal transition(EMT)related proteins(N-cadherin,Snail,vimentin and E-cadherin)were detected by qRT-PCR and Western blot.Results:The expression level of SCD1 in TPC1 was significantly higher than that in Nthy-ori 3-1,BCPAP and K1(P<0.05).Compared with the blank control group(Control)and the control interference group(si-NC),the expression of SCD1 mRNA and protein in the interference SCD1 group(si-SCD1)was significantly decreased(P<0.05).The proliferation,migration and invasion of TPC1 cells were significantly inhibited after interfering with SCD1(P<0.05).It was also found that interfering SCD1 could increase the expression of E-cadherin protein while the expression of vimentin,Snail and N-cadherin protein were inhibited significantly(P<0.05).Conclusion:Interfering SCD1 was able to inhibit the proliferation,migration and invasion of thyroid papillary cancer cell TPC1 with the potential mechanism by inhibition of the EMT procedure.

Importance and Risk Prediction of ABO Blood Group and Rh Factor in Papillary Thyroid Cancer

Objective:There are limited data in the literature regarding the potential relationship between thyroid cancer and ABO blood types and Rh factor.The aim of our study was to investigate whether papillary thyroid cancer(PTC)is associated with blood type.Materials and Methods:The present study included patients who pre­sented to Dicle University Faculty of Medicine between June 2009 and December 2020 and were diagnosed with PTC as a result of postoperative(thyroidectomy)histopathological analysis.The control group consisted of individuals whose blood type was analyzed at a random blood center.Results:Of the 223 patients diagnosed with PTC,163(73.1%)were fe­males and 60(26.9%)were males.In the comparison of patients based on ABO blood types and Rh factor,A Rh positive blood type was found 31%less frequently in the PTC group compared with the control group,and thus it was associated with a lower risk of PTC(OR:0.69;95%Confidence In­terval:0.50-0.96,p=0.029).Conclusions:In our study,we found A Rh positive blood type to be signifi­cantly less frequent among patients with PTC.A Rh positive blood type can be considered as a protective factor indicating a reduced risk of PTC.

Predictive Value of BRAF^V600E Mutation for Lymph Node Metastasis in Papillary Thyroid Cancer:A Meta-analysis

BRAF^V600E mutation has been thought to be a valuable molecular marker that may predict a worse prognosis for papillary thyroid cancer (PTC).But whether BRAF^V600E mutation is associated with lymph node metastasis (LNM)remains controversial. Different surgical strategies may bring a bias in demonsstrating the association between them.In order to delineate a risk stratification to guide a tailored initial approach to tumors that express BRAF^V600E mutation,we performed this meta-analysis by using the articles in which total or near-total thyroidectomy plus bilateral central lymph node dissection was routinely performed to avoid the bias from the surgical strategy.We searched the Medline,Embase and CNKI database for eligible studies from January 2003 to May 2018.Meta-analysis was performed using the STATA 12.0 software.Odds ratios (ORs)and 95% confidence intervals (CIs)were calculated under fixed-effects or random-effects models.Fifteen clinical studies were included with a total of 4909 PTC patients. Our meta-analysis results reported that BRAF^V600E mutation was associated with LNM (OR=1.34;95% CI:1.09-1.65;P=0.005),as well as central LNM (OR=1.59;95% CI: 1.35-1.88;P<0.00001).Moreover,in patients with papillary thyroid microcarcinoma, we also confirmed the predictive value of BRAF^V600E mutation for LNM (OR=3.49;95% CI:2.02-6.02;P<0.00001).This meta-analysis demonstrates that BRAF^V600E mutation is closely related to LNM in PTC patients.The results suggest that BRAF^V600E mutation can be considered as a risk factor for LNM in PTC.Moreover,combining BRAF^V600E mutation with other risk factors to determine the initial surgical treatment may bring benefits for PTC patients.

BRAF^(V600E) vs. TIRADS in predicting papillary thyroid cancers in Bethesda system Ⅰ, Ⅲ, and Ⅴ nodules

Objective: Bethesda System for Reporting Thyroid Cytopathology(BSRTC) categories Ⅰ, Ⅲ, and Ⅴaccount for a significant proportion of fine needle aspiration cytology(FNAC) diagnoses. This study aimed to compare the diagnostic efficacy of BRAF^(V600E) mutation and the Thyroid Imaging Reporting and Data System(TIRADS) classification in differentiating papillary thyroid cancers(PTCs) from benign lesions among BSRTC I, III, and V nodules.Methods: A total of 472 patients with 479 nodules were enrolled in this prospective study. Ultrasound, BRAF^(V600E) mutation testing, and FNAC were performed in each nodule, followed by surgery or regular ultrasound examination.Results: In the BSRTC I category, BRAF^(V600E) showed similar sensitivity, higher specificity, and lower accuracy when compared with TIRADS. In the BSRTC III/V category, the sensitivity, specificity, and accuracy of BRAF^(V600E) were similar to those of TIRADS. In comparison to BRAF^(V600E) alone, the combination of the two methods significantly improved sensitivity(BSRTC Ⅰ:93.6% vs. 67.7%, P < 0.01; BSRTC Ⅲ: 93.8% vs. 75.0%, P < 0.01; BSRTC V: 96.0% vs. 85.3%, P < 0.001). When compared with TIRADS alone, the combination improved sensitivity in BSRTC Ⅰ nodules(93.6% vs. 74.2%, P < 0.05), increased sensitivity and decreased accuracy in BSRTC III nodules(93.8% vs. 75.0%, P < 0.01, 91.0% vs. 93.6%, P < 0.01), and improved both sensitivity and accuracy in BSRTC V nodules(96.0% vs. 82.0%, P < 0.001; 94.2% vs. 81.3%, P < 0.001).Conclusions: BRAF^(V600E) exhibited higher specificity and lower accuracy compared with TIRADS in BSRTC Ⅰ nodules, while the two methods showed similar diagnostic value in BSRTC Ⅲ/Ⅴ nodules. The combination of the two methods distinctly improved sensitivity in the diagnosis of PTCs in BSRTC Ⅰ, Ⅲ, and Ⅴ nodules.

Strong Correlation of Abnormal Serum and Urinary Iodine Levels with Papillary Thyroid Cancer:A Case-control Study

Thyroid cancer is the most common malignancy of the endocrine system,and its incidence is increasing worldwide.In China,its incidence has increased from 1.78/104 in 1988 to 10.58/104 in2013.Thyroid cancers are mainly classified into papillary thyroid cancer(PTC),follicular thyroid cancer(FTC),medullary thyroid cancer(MTC).

Complication versus Radicality in Papillary Thyroid Cancer Surgery: How to Keep the Balance?

Background: Controversy exists over the extent of surgical treatment of papillary thyroid cancer.Reoperations may carry a significant risk of surgical complications. The aim of this study is to investigate the complications following surgical treatment of thyroid cancer and the association between the?extent of surgery and complication rates. Methods: A total of 196 patients with papillary thyroid cancer were retrospectively reviewed to identify extent of surgery and associated complications, between 2009 and 2018 atSouth Egypt Cancer Institute Assiut University. Results: Primary procedures included less-than-total thyroidectomy (near total thyroidectomy in 5.1%, subtotal thyroidectomy in 4.1%, thyroid lobectomy in 3.1%) and total thyroidectomy in 87.8% (18.9% of them are completion thyroidectomy). No lymph nodes dissection was done in 10.7%, Berry picking in 6.1%, central compartment neck dissection in 41.8%, central compartment neck dissection with modified ipsilateral radical neck dissection in 12.2%, central compartment neck dissection with modified bilateral radical neck dissection in 26.0%, central compartment dissection with both modified bilateral radical neck dissection and superior mediastinal lymph node dissection 3.1%. The most common surgical complication were transient hypoparathyroidism (16.7% - 45.8%) and 2.0% permanent, transient vocal cord palsy (7.3% - 16.7%), and 3.9% permanent, hematoma 1.5%, seroma 7.1% and chyle fistula in 2.6% of patients. Conclusion: Thyroid cancer surgeries are safe. The transient complication rates of hypoparathyroidism increased significantly with increasing the extent of surgery.

Risk stratification for radioactive iodine refractoriness using molecular alterations in distant metastatic differentiated thyroid cancer

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied.Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel(Thyro Lead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification(MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS.Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIRDTC. Genetic alterations were identified in 90% of all the patients, with BRAF(59.7% vs. 17.3%), TERT promoter(43.9% vs. 7.4%), and TP53 mutations(11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions(15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness(P<0.001), with an odds ratio(OR) of high to low MRS of 7.52 [95%confidence interval(95% CI), 3.96-14.28;P<0.001] and an OR of intermediate to low MRS of 3.20(95% CI,1.01-10.14;P=0.041).Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.

Correlation of the BRAFV600E and RAS mutations with clinicopathological characteristics of papillary thyroid cancer using TCGA database analysis

Objective:To investigate the occurrence of BRAFV600E and RAS mutations in thyroid papillary carcinoma (PTC) and to study their correlation with clinicopathological features of PTC. Methods Relevant information of PTC was downloaded and organized from The Cancer Genome Atlas (TCGA) via cBioPortal, then the gene mutation and clinical information of 402 PTC samples were analyzed. The correlation of BRAFV600E and RAS mutations with clinicopathological features and prognosis of PTC were subjected to univariate analysis. Secondly, we use Binary Logistic multivariate analysis to analyze the factors screened above. Results BRAFV600E mutation rate is 48.5% (195/402) and RAS mutation rate is 10.2% (41/402) in 402 cases of PTC. Univariate analysis showed that BRAFV600E mutation has nothing to do with age and sex of the patient. There is a significant correlation among BRAFV600E mutation and lymph node metastasis, extrathyroidal invasion, staging, recurrence, progression and pathological subtypes in PTC. There is no significant correlation among RAS and age, sex, staging, recurrence, progression. There is a significant correlation among RAS and lymph node metastasis, extrathyroidal invasion and pathological subtypes in PTC. Multivariate logistic regression analysis indicated that there is a significant correlation among BRAFV600E mutation and extrathyroidal invasion, pathological subtypes in PTC. There is a significant correlation among RAS and lymph node metastasis, extrathyroidal invasion and pathological subtypes in PTC.ConclusionThe mutation rate of BRAFV600E was significantly higher than that of RAS in PTC. Mutations in BRAFV600E and RAS can be used as predictors of prognosis in PTC.

MicroRNAs in thyroid cancer with focus on medullary thyroid carcinoma:potential therapeutic targets and diagnostic/prognostic markers and web based tools

This review aimed to describe the inculpation of microRNAs(miRNAs)in thyroid cancer(TC)and its subtypes,mainly medullary thyroid carcinoma(MTC),and to outline web-based tools and databases for bioinformatics analysis of miRNAs in TC.Additionally,the capacity of miRNAs to serve as therapeutic targets and biomarkers in TC management will be discussed.This review is based on a literature search of relevant articles on the role of miRNAs in TC and its subtypes,mainly MTC.Additionally,web-based tools and databases for bioinformatics analysis of miRNAs in TC were identified and described.MiRNAs can perform as oncomiRs or antioncoges,relying on the target mRNAs they regulate.MiRNA replacement therapy using miRNA mimics or antimiRs that aim to suppress the function of certain miRNAs can be applied to correct miRNAs aberrantly expressed in diseases,particularly in cancer.MiRNAs are involved in the modulation of fundamental pathways related to cancer,resembling cell cycle checkpoints and DNA repair pathways.MiRNAs are also rather stable and can reliably be detected in different types of biological materials,rendering them favorable diagnosis and prognosis biomarkers as well.MiRNAs have emerged as promising tools for evaluating medical outcomes in TC and as possible therapeutic targets.The contribution of miRNAs in thyroid cancer,particularly MTC,is an active area of research,and the utility of web applications and databases for the biological data analysis of miRNAs in TC is becoming increasingly important.

COL4A2 enhances thyroid cancer cell proliferation through the AKT pathway

Objectives:Thyroid cancer(THCA)is the most common malignant tumor in endocrine system and the incidence has been increasing worldwide.And the number of patients dying from THCA has also gradually risen because the incidence continues to increase,so the mechanisms related to effective targets is necessary to improve the survival.This study was to preliminarily investigate the effects of the COL4A2 gene on the regulation of thyroid cancer(THCA)cell proliferation and the associated pathways.Methods:Bioinformatics analysis revealed that COL4A2 was closely associated with cancer development.COL4A2 expression in THCA tissues was analyzed using immunohistochemistry,and survival information was determined via Kaplan-Meier curves.The expression of COL4A2 and AKT pathway-related genes were analyzed using qPCR and western blot analyses.Colony formation as well as CCK-8 assays exhibited the cell proliferation level and cell activity,respectively.Downstream of COL4A2 was identified by Gene set enrichment analysis(GSEA).The effects of the COL4A2 and AKT pathways on THCA tumor growth in vivo were determined using a mouse model.Results:Bioinformatics analysis exhibited that COL4A2 plays a significant role in cancer and that the AKT pathway is downstream of COL4A2.THCA patients with high COL4A2 expression had shorter recurrence-free survival.Upregulation of COL4A2 gene expression in 2 THCA cell lines promoted tumor cell growth and activity.The use of AKT pathway blockers also restrained the growth and activity of the 2 THCA cell lines.The use of AKT pathway blockers reduced tumor volume and mass and prolonged mouse survival.Conclusions:COL4A2 can promote the growth as well as development of THCA through the AKT pathway and COL4A2 could be used as a target for THCA.

A Study on the Explainability of Thyroid Cancer Prediction:SHAP Values and Association-Rule Based Feature Integration Framework

In the era of advanced machine learning techniques,the development of accurate predictive models for complex medical conditions,such as thyroid cancer,has shown remarkable progress.Accurate predictivemodels for thyroid cancer enhance early detection,improve resource allocation,and reduce overtreatment.However,the widespread adoption of these models in clinical practice demands predictive performance along with interpretability and transparency.This paper proposes a novel association-rule based feature-integratedmachine learning model which shows better classification and prediction accuracy than present state-of-the-artmodels.Our study also focuses on the application of SHapley Additive exPlanations(SHAP)values as a powerful tool for explaining thyroid cancer prediction models.In the proposed method,the association-rule based feature integration framework identifies frequently occurring attribute combinations in the dataset.The original dataset is used in trainingmachine learning models,and further used in generating SHAP values fromthesemodels.In the next phase,the dataset is integrated with the dominant feature sets identified through association-rule based analysis.This new integrated dataset is used in re-training the machine learning models.The new SHAP values generated from these models help in validating the contributions of feature sets in predicting malignancy.The conventional machine learning models lack interpretability,which can hinder their integration into clinical decision-making systems.In this study,the SHAP values are introduced along with association-rule based feature integration as a comprehensive framework for understanding the contributions of feature sets inmodelling the predictions.The study discusses the importance of reliable predictive models for early diagnosis of thyroid cancer,and a validation framework of explainability.The proposed model shows an accuracy of 93.48%.Performance metrics such as precision,recall,F1-score,and the area under the receiver operating characteristic(AUROC)are also higher than the baseline models.The results of the proposed model help us identify the dominant feature sets that impact thyroid cancer classification and prediction.The features{calcification}and{shape}consistently emerged as the top-ranked features associated with thyroid malignancy,in both association-rule based interestingnessmetric values and SHAPmethods.The paper highlights the potential of the rule-based integrated models with SHAP in bridging the gap between the machine learning predictions and the interpretability of this prediction which is required for real-world medical applications.

Anaplastic thyroid cancer: Unveiling advances in diagnosis andmanagement

The review article by Pavlidis et al published in World J Clin Oncol provides a meticulous analysis of the intricacies surrounding anaplastic carcinoma of the thyroid.Thyroid carcinoma encompasses a spectrum of diseases,each charac-terized by distinct behaviors and outcomes.Diagnostic approaches encompass a diverse array of tools.Surgery remains the pivotal treatment for anaplastic thyroid carcinoma.Radiotherapy and chemotherapy offer the best overall sur-vival in aggressive disease.Combinations of immunotherapy with targeted the-rapies,such as dabrafenib-trametinib,demonstrate potential for enhanced effect-iveness and improved survival outcomes.Multifaceted approach fuelled by precision medicine and interdisciplinary collaboration is imperative in charting a course toward improved outcomes in this formidable malignancy.