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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-12-08

AUTHORS

Ove Bruland, Øystein Fluge, Lars A Akslen, Hans G Eiken, Johan R Lillehaug, Jan E Varhaug, Per M Knappskog

ABSTRACT

BACKGROUND: Members of the PDGF family have been suggested as potential biomarkers for papillary thyroid carcinomas (PTC). However, it is known that both expression and stimulatory effect of PDGF ligands can be affected by inflammatory cytokines. We have performed a microarray study in a collection of PTCs, of which about half the biopsies contained tumour-infiltrating lymphocytes or thyroiditis. To investigate the expression level of PDGF ligands and receptors in PTC we measured the relative mRNA expression of all members of the PDGF family by qRT-PCR in 10 classical PTC, eight clinically aggressive PTC, and five non-neoplastic thyroid specimens, and integrated qRT-PCR data with microarray data to enable us to link PDGF-associated gene expression profiles into networks based on recognized interactions. Finally, we investigated potential influence on PDGF mRNA levels by the presence of tumour-infiltrating lymphocytes. METHODS: qRT-PCR was performed on PDGFA, PDGFB, PDGFC, PDGFD, PDGFRA PDGFRB and a selection of lymphocyte specific mRNA transcripts. Semiquantitative assessment of tumour-infiltrating lymphocytes was performed on the adjacent part of the biopsy used for RNA extraction for all biopsies, while direct quantitation by qRT-PCR of lymphocyte-specific mRNA transcripts were performed on RNA also subjected to expression analysis. Relative expression values of PDGF family members were combined with a cDNA microarray dataset and analyzed based on clinical findings and PDGF expression patterns. Ingenuity Pathway Analysis (IPA) was used to elucidate potential molecular interactions and networks. RESULTS: PDGF family members were differentially regulated at the mRNA level in PTC as compared to normal thyroid specimens. Expression of PDGFA (p = 0.003), PDGFB (p = 0.01) and PDGFC (p = 0.006) were significantly up-regulated in PTCs compared to non-neoplastic thyroid tissue. In addition, expression of PDGFC was significantly up-regulated in classical PTCs as compared to clinically aggressive PTCs (p = 0.006), and PDGFRB were significantly up-regulated in clinically aggressive PTCs (p = 0.01) as compared to non-neoplastic tissue. Semiquantitative assessment of lymphocytes correlated well with quantitation of lymphocyte-specific gene expression. Further more, by combining TaqMan and microarray data we found a strong inverse correlation between PDGFC expression and the expression of lymphocyte specific mRNAs. CONCLUSION: At the mRNA level, several members of the PDGF family are differentially expressed in PTCs as compared to normal thyroid tissue. Of these, only the PDGFC mRNA expression level initially seemed to distinguish classical PTCs from the more aggressive PTCs. However, further investigation showed that PDGFC expression level correlated inversely to the expression of several lymphocyte specific genes, and to the presence of lymphocytes in the biopsies. Thus, we find that PDGFC mRNA expression were down-regulated in biopsies containing infiltrated lymphocytes or thyroiditis. No other PDGF family member could be linked to lymphocyte specific gene expression in our collection of PTCs biopsies. More... »

PAGES

425-425

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1471-2407-9-425

DOI

http://dx.doi.org/10.1186/1471-2407-9-425

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1022768497

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19968886


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62 clinical findings
63 collection
64 collection of PTCs
65 correlation
66 cytokines
67 data
68 dataset
69 direct quantitation
70 effect
71 expression
72 expression analysis
73 expression levels
74 expression of PDGFA
75 expression of PDGFC
76 expression patterns
77 expression profiles
78 expression values
79 extraction
80 family
81 family members
82 findings
83 further investigation
84 gene expression
85 gene expression profiles
86 genes
87 human papillary thyroid carcinoma
88 infiltration
89 inflammatory cytokines
90 influence
91 interaction
92 inverse correlation
93 investigation
94 levels
95 ligands
96 lymphocyte infiltration
97 lymphocyte specific mRNA transcripts
98 lymphocyte specific mRNAs
99 lymphocyte-specific gene expression
100 lymphocyte-specific genes
101 lymphocytes
102 mRNA
103 mRNA expression
104 mRNA expression levels
105 mRNA levels
106 mRNA transcripts
107 members
108 microarray data
109 microarray datasets
110 microarray studies
111 molecular interactions
112 network
113 non-neoplastic thyroid specimens
114 non-neoplastic thyroid tissue
115 non-neoplastic tissues
116 normal thyroid specimens
117 normal thyroid tissue
118 papillary thyroid carcinoma
119 part
120 pathway analysis
121 patterns
122 potential biomarkers
123 potential influence
124 potential molecular interactions
125 presence
126 presence of lymphocytes
127 profile
128 qRT-PCR
129 qRT-PCR data
130 quantitation
131 receptors
132 relative expression values
133 relative mRNA expression
134 selection
135 semiquantitative assessment
136 specific gene expression
137 specific genes
138 specific mRNA transcripts
139 specific mRNAs
140 specimens
141 stimulatory effect
142 strong inverse correlation
143 study
144 thyroid carcinoma
145 thyroid specimens
146 thyroid tissue
147 thyroiditis
148 tissue
149 transcripts
150 tumor-infiltrating lymphocytes
151 values
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