Transforming Growth Factor-Beta Polymorphisms and Serum Level in the Development of Osteosarcoma

Abstract

The transforming growth factor-beta (TGF-β) signaling pathway plays critical roles in the development of various diseases. The current study investigated whether TGF-β was involved in the pathogenesis of osteosarcoma from the genetic polymorphism perspective and serum level perspective. We first examined two TGF-β1 polymorphisms, rs1800469C/T and rs1800470T/C, in 202 osteosarcoma patients and 216 healthy controls. Data revealed that the prevalence of rs1800470TT genotype and T allele was significantly elevated in patients than in controls (odds ratio [OR]=2.28, 95% confidence interval [CI]: 1.30-3.98, p<0.001, and OR=1.49, 95% CI: 1.14-1.96, p<0.001). Function analyses showed that healthy controls carrying rs1800470TT genotype had a significantly higher serum level of TGF-β than those carrying the rs1800470CC genotype (191.1±15.7 pg/mL vs. 129.4±10.9 pg/mL, p=0.003). We then compared the serum level of TGF-β between osteosarcoma patients and healthy controls. Results demonstrated a significantly increased serum level of TGF-β in patients than in controls. Further analyses identified that patients with metastasis had augmented levels of serum TGF-β than those without metastasis. These data indicate that TGF-β may be closely involved in the pathogenesis of osteosarcoma.

Correlation between TGF-β1 gene 29 T > C single nucleotide polymorphism and clinicopathological characteristics of osteosarcoma

“…This study assessed the relationship between the SNPs (29 T>C, 509C>T, 869 T>C) and osteosarcoma risk, which concludes that only 29 T>C genotype frequency distribution has obvious difference within the patient group and control group as patients carrying TT genotype have higher morbidity of osteosarcoma than patients carrying CC genotype (OR=2.10, 95 % CI=1.08-4.05). In a research including 202 patients with osteosarcoma and 216 healthy controls, Xu and other researchers have found that rs1800470 TT genotype is relevant to the morbidity of osteosarcoma [16], which is in conformity with our research results. Xu made further comparison with the level of serum TGF-β1 between the patient group and control group and thus he found that the patient group has higher level of serum TGF-β1.…”

“…The promoter SNP 509C>T reportedly contributes to osteoporosis by influencing bone mass [14,15]. Xu found that rs1800470TT genotype carriers have higher morbidity rate of osteosarcoma and rs1800470TT genotype patients with osteosarcoma have higher level of TGF-β1 in their serum than rs1800470CC genotype patients [16]. Therefore, we conducted a case-control study to examine whether TGF-β1 SNPs(29 T>C, 509C>T, 869 T>C) modifies osteosarcoma risk and prognosis.…”

Molecular characterization of metastatic osteosarcoma: Differentially expressed genes, transcription factors and microRNAs

“…Altered TGF-β expression was previously observed in patients with metastatic osteosarcoma compared with in patients without metastasis (29). In addition, TGF-β may increase the metastatic potential of human osteosarcoma cells by triggering the malignant phenotype presentation of hyaluronan and versican (30).…”

The association of functional polymorphisms in genes encoding growth factors for endothelial cells and smooth muscle cells with the severity of coronary artery disease

“…However, at levels exceeding 1–2 fg/cell, TGF-β1 may stimulate SMC, fibroblast and chondrocyte proliferation [39]. TGF-β1 is also found in blood serum, although studies aiming to compare TGF-β1 levels and CAD severity yielded conflicting results [5, 40–42]; additionally, TGF-β1 levels depend on genetic factors [43–46]. Some researchers have associated the C alleles with higher TGF-β1 levels [44–46], whereas other authors have postulated higher levels in T/T homozygotes [44].…”