Inverse correlation between PDGFC expression and lymphocyte infiltration in human papillary thyroid carcinomas

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• Platelet-derived growth factor (PDGF) family members are implicated as potential biomarkers for papillary thyroid carcinomas (PTCs).
• Inflammatory cytokines can influence PDGF ligand expression and activity, suggesting a potential interaction in the tumor microenvironment.
• Previous studies have indicated differential expression of PDGF family members in various cancers, but their specific role in PTC, particularly concerning tumor-infiltrating lymphocytes, requires further investigation.

Purpose of the Study:

• To investigate the mRNA expression levels of all PDGF family members and their receptors in classical PTC, clinically aggressive PTC, and non-neoplastic thyroid tissue.
• To integrate gene expression data with microarray analysis to identify PDGF-associated gene expression networks.
• To determine the influence of tumor-infiltrating lymphocytes (TILs) on PDGF mRNA levels in PTC.

Main Methods:

• Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was employed to measure the relative mRNA expression of PDGFA, PDGFB, PDGFC, PDGFD, PDGFRA, and PDGFRB.
• Lymphocyte-specific mRNA transcripts were quantified using qRT-PCR, and semiquantitative assessment of TILs was performed on adjacent biopsy sections.
• qRT-PCR data were integrated with a cDNA microarray dataset, and Ingenuity Pathway Analysis (IPA) was utilized to explore molecular interactions and networks.

Main Results:

• PDGF family members PDGFA, PDGFB, and PDGFC showed significantly higher mRNA expression in PTCs compared to non-neoplastic thyroid tissue.
• PDGFC mRNA was significantly up-regulated in classical PTCs versus clinically aggressive PTCs, while PDGFRB was significantly up-regulated in aggressive PTCs versus normal tissue.
• A strong inverse correlation was observed between PDGFC expression and the expression of lymphocyte-specific mRNAs, indicating PDGFC levels decrease with increased lymphocyte infiltration.

Conclusions:

• Several PDGF family members exhibit differential mRNA expression in PTCs compared to normal thyroid tissue.
• PDGFC mRNA expression is inversely correlated with the presence of tumor-infiltrating lymphocytes and thyroiditis, suggesting a down-regulation in inflamed PTC biopsies.
• Unlike other PDGF family members, PDGFC expression is linked to lymphocyte-specific gene expression, highlighting its potential role in the interplay between PDGF signaling and the immune microenvironment in PTC.