Low expression of TFF3 in papillary thyroid carcinoma may correlate with poor prognosis but high immune cell infiltration

Future Oncol. 2022 Jan;18(3):333-348. doi: 10.2217/fon-2020-1183. Epub 2021 Nov 10.

Abstract

Background: Papillary thyroid carcinoma (PTC) is one of the most common endocrine malignancies and has a favorable prognosis. However, optimal treatments and prognostic markers have not been clearly identified. Methods: Gene expression data from primary PTC were downloaded from the Gene Expression Omnibus database and subjected to two analyses of differentially expressed genes (DEGs), followed by intersecting individual and integrated DEGs analyses as well as gene set enrichment analysis. Analysis of data from Sequence Read Archive and The Cancer Genome Atlas, immunohistochemistry and qRT-PCR of TFF3 were performed to validate the results. Finally, the relationship between gene expression and disease-free survival as well as immune cell infiltration were investigated. Results: Six critical DEGs and several tumor-enriched signaling pathways were identified. Immunohistochemistry and qRT-PCR validated the low expression of TFF3 in PTC. TFF3 and FCGBP are coexpressed in PTC, and patients with lower gene expression had worse disease-free survival but higher immune cell infiltration. Conclusion: TFF3 was significantly underexpressed and may function with FCGBP synergistically in PTC.

Keywords: TFF3; differentially expressed genes; immune cell infiltration; papillary thyroid carcinoma; prognosis prediction.

Plain language summary

Lay abstract Thyroid cancers are some of the most common endocrine malignancies. However, the optimal treatments and prognostic markers have not been clearly identified. We identified six critical differentially expressed genes and several tumor-enriched signaling pathways in papillary thyroid carcinoma, and found that TFF3 was the most underexpressed gene, as validated by experiment. In addition, TFF3 and FCGBP worked synergistically and may mark prognosis and tumor immune cell infiltration, which may benefit patients with papillary thyroid carcinoma by providing early indication and prompting further basic investigation.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Cell Adhesion Molecules / analysis
  • Cell Adhesion Molecules / genetics
  • Datasets as Topic
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / immunology
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / genetics
  • Risk Assessment / methods
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Cancer, Papillary / immunology
  • Thyroid Cancer, Papillary / mortality*
  • Thyroid Cancer, Papillary / surgery
  • Thyroid Gland / immunology
  • Thyroid Gland / pathology
  • Thyroid Gland / surgery
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / immunology
  • Thyroid Neoplasms / mortality*
  • Thyroid Neoplasms / surgery
  • Thyroidectomy
  • Trefoil Factor-3 / analysis
  • Trefoil Factor-3 / genetics*
  • Tumor Microenvironment / immunology

Substances

  • Biomarkers, Tumor
  • Cell Adhesion Molecules
  • FCGBP protein, human
  • TFF3 protein, human
  • Trefoil Factor-3