Evaluation of the expression pattern and diagnostic value of PPARγ in malignant and benign primary bone tumors

Abstract

Purpose The quantifiable description of PPARγ expression pattern beside mechanistic in-vitro evidence will provide insights into the involvement of this mediator in tumor pathogenesis. This study is focused on illuminating the PPARγ gene and protein expression pattern, its association with tumor deterioration and its diagnostic value in different types of primary bone tumors. Methods The expression pattern of PPARγ was investigated in the 180 bone tissues including 90 bone tumor tissues and 90 non-cancerous bone tissues. The local PPARγ expression level was assessed using real-time qRT-PCR and the PPARγ protein expression pattern was measured using immunohistochemistry. The correlation of PPARγ expression level with patients’ clinic-pathological features, also the value of the variables in predicting PPARγ expression level in tumors and the value of PPARγ to discriminate tumor subtypes were assessed. Results The mean PPARγ mRNA expression was significantly higher in bone tumors compared to healthy bone tissues, also the malignant tumors including osteosarcoma and Ewing sarcoma had the elevated level of PPARγ mRNA compared to GCT tumors. Consistently, the protein expression of PPARγ in the tumor site was significantly higher in the bone tumors and malignant tumors compared to non-cancerous and benign tumors, respectively. The PPARγ protein could predict malignant tumor features including tumor grade, metastasis and recurrence significantly. Moreover, PPARγ could potentially discriminate the patients from the controls also malignant tumors from benign tumors with significant sensitivity and specificity. Conclusions PPARγ might be involved in primary bone tumor pathogenesis and determining its molecular mechanism regarding bone cancer pathogenesis is of grave importance.

Cytoplasmic PPARγ Significantly Correlates With P53 Immunohistochemical Expression and Tumor Size in Localized Tenosynovial Giant Cell Tumor

“…The PPAR family members are ligand-activated transcription factors with three isotypes, PPAR α, γ, and δ. PPARγ plays a crucial role in glucose metabolism, fatty acid oxidation, cell cycle regulation, adipocyte differentiation, lipid storage, and inflammation [ 13 ]. The exact role of PPARγ in tumors as oncogenic versus tumor suppressive remains controversial [ 23 ]. PPARγ association with neoplastic pathogenesis has recently been increasingly recognized.…”

“…Contrary to our results, another study reported that induced PPARγ upregulation is associated with wide TGCT tumor necrosis [ 15 ]. The differences in reported results can be explained by the varying role of PPARγ depending on varying tumors, individual characters, and PPARγ concentration [ 23 ]. Moreover, although PPARγ is a nuclear receptor transcription factor, different subcellular locations of IHC expression were described in the literature and were associated with different neoplastic features and prognoses [ 13 , 23 , 30 ].…”

“…Threshold adjustment was carried out with the removal of background signals but without the elimination of real signals. The chosen threshold was applied to all IHC photos [ 23 , 24 ]. Two pathologists scored the IHC-stained slides independently, and the mean of the two pathologists' scores/10 HPFs/slide was reported.…”

The clinical significance of CD44v6 in malignant and benign primary bone tumors

“…The anti-CD44v6 antibody (Catalog number: ab217902; Abcam) with the dilution of 1:500 and anti-mouse IgG HRP-conjugated secondary antibody (Catalog number: ab6728; Abcam) was applied for staining and detection. The detail of the protocol and analysis is based on the protocol described in our previous study [ 27 , 28 ]. Briefly, tissue blocks were prepared in optimal cutting temperature (OCT) embedding medium and fixed in paraformaldehyde (4%).…”

“…The non-specific antigenic sites on tissue sections were blocked using goat serum (10%) and the intensity of staining was visualized using horseradish peroxidase activity and chromogens. The percentages of CD44v6 intensity for each sample were measured using Image J software [ 28 ] and presented as graphs (Fig. 1 ).…”