Evidence map›Paper›PMID 40450370›Full record

ArticleHereditas2025

Deciphering the role of Hashimoto's Thyroiditis-related key genes in thyroid cancer via detailed in silico analysis followed by the experimental validation.

Mostafa A Abdel-Maksoud, Taghreed N Almana, Saeedah Almutair, Abdulaziz Alamri, Ibrahim A Saleh, Mohamed Y Zaky, Wahidah H Al-Qahtani, Yasir Hameed

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Hereditas, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Mostafa A Abdel-MaksoudDepartment of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, 11451, Riyadh, Saudi Arabia. Mabdmaksoud@ksu.edu.sa.
Taghreed N AlmanaDepartment of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, 11451, Riyadh, Saudi Arabia.
Saeedah AlmutairDepartment of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, 11451, Riyadh, Saudi Arabia.
Abdulaziz AlamriBiochemistry Department-College of Science-King, Saud University, Riyadh, Saudi Arabia.
Ibrahim A SalehFaculty of Science, Zarqa University, Zarqa, 13110, Jordan.
Mohamed Y ZakyUPMC Hillman Cancer Center, Division of Hematology and Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Wahidah H Al-QahtaniDepartment of Food Sciences & Nutrition, College of Food and Agricultural Sciences, King Saud University, P.O. Box 270677, 11352, Riyadh, Saudi Arabia.
Yasir HameedDepartment of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur, Pakistan. yasirhameed2011@gmail.com.

Funding

King Saud University, Riyadh, Saud Arabia RSPD2024R632
6 · The paper itself

Abstract

backgroundThyroid cancer, characterized by significant genetic and epigenetic alterations, remains a critical focus of molecular oncology. This study investigates eight key genes (BRAF, EIF1 AX, FOXE1, KRAS, PDGFRA, PIK3 CA, PTEN, and TERT) that are deregulated in Hashimoto's Thyroiditis and their roles in thyroid cancer.

methodsCell culture, nucleic acid extraction, RT-qPCR, bisulfite sequencing, and various in silico tools and databases.

resultsExpression analysis using RT-qPCR revealed significant (p-value < 0.05) down-regulation of BRAF, EIF1 AX, FOXE1, KRAS, PDGFRA, PIK3 CA, PTEN, and TERT genes in thyroid cancer cell lines compared to controls, with ROC curves indicating high diagnostic accuracy (AUC 0.93-0.99). Bisulfite sequencing demonstrated increased promoter methylation across all eight genes in cancerous samples, suggesting epigenetic silencing as a regulatory mechanism. Validation through UALCAN, OncoDB, and HPA confirmed reduced gene and protein expression in additional thyroid cancer cohorts. Genetic alteration analysis via cBioPortal showed prevalent BRAF mutations, whereas other genes exhibited fewer alterations. Kaplan-Meier survival analysis linked lower expression of BRAF and PIK3 CA to poorer overall survival. Correlation studies using TISIDB and TISCH2 databases highlighted associations between gene expression and immune modulation, revealing significant correlations with immune cell infiltration and diverse immune subtypes. Moreover, miRNA-mRNA network analysis identified hsa-mir- 628 - 5p as a critical regulator targeting these genes. The impact of BRAF overexpression on SW579 cells was assessed through various functional assays. Overexpression of BRAF resulted in reduced cell proliferation, colony formation, and wound healing, which may reflect context-dependent effects. While BRAF is typically oncogenic, its overexpression may lead to cellular stress or negative feedback mechanisms that impair these processes.

conclusionThis comprehensive analysis elucidates the complex regulatory landscape of these genes in thyroid cancer, emphasizing the significant role of epigenetic modifications and providing insights into potential diagnostic and therapeutic avenues.

Indexed as

Hashimoto DiseaseThyroid NeoplasmsCell Line, TumorComputer SimulationDNA MethylationEpigenesis, GeneticGene Expression Regulation, NeoplasticHumansMutationProto-Oncogene Proteins B-rafBRAF protein, humanProto-Oncogene Proteins B-rafDiagnosisHashimoto’s ThyroiditisPrognosisThyroid cancerTreatment

Identifiers

PMID40450370
PMCPMC12126899

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.