scholarly journals Transforming growth factor beta signaling in hepatocellular carcinoma: as a victim or culprit?

2019 ◽  
Vol 6 (3) ◽  
pp. 991
Author(s):  
Varun Kumar Sharma ◽  
Charu Tyagi ◽  
Yugandhar P. Reddy ◽  
Jayanand Manjhi ◽  
Lomas Kumar Tomar
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Signalling Pathway ◽  
Expression Of Genes ◽  
Tgfβ Signalling ◽  
Growth Factor Beta ◽  
Tgfβ Pathway

The transforming growth factor-β (TGFβ) signalling pathway control various cellular function and play a pivotal role in tumour suppression. In contrary, overexpression of TGFβ is linked to promote the cancer development. TGFβ facilitate cell-growth and cell-differentiation process which support tumour propagation. In case of hepatocellular carcinoma (HCC), TGFβ signalling pathway is the master regulator of HCCs pathogenesis and functionally involved in the regulation of HCCs phenotype via modulating the downstream signalling pathways. In this article, we have highlighted the contradictory behaviour of TGFβ in hepatocellular carcinoma. Observations suggest that the TGFβ signalling pathway is positively correlated to the expression of genes linked with various hepatic pathological conditions, including fibrosis, cirrhosis, inflammation and cancer. TGFβ pathway play dual role as pro and anti-tumoural activities in cancer cells depending on their context.

Association between genetic variations in transforming growth factor beta pathway and overall survival in patients with non-small cell lung cancer treated with definitive radiotherapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17530-e17530
Author(s):  
Weili Wang ◽  
Kerby A Shedden ◽  
Feng-Ming (Spring) Kong
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Definitive Radiotherapy ◽  
Growth Factor Beta ◽  
Tgfβ Pathway

e17530 Background: The transforming growth factor beta (TGFβ) pathway, an important regulator in cellular metabolic process, has been reported for significant association with cancer prognosis. This study was to exam the association between single nucleotide polymorphisms (SNPs) of TGFβ pathway and overall survival (OS) in subjects with non-small cell lung cancer (NSCLC). Methods: Patients with stage I-III NSCLC received definitive radiotherapy with/without chemotherapy were eligible to this prospective study. The primary endpoint was OS which was calculated from radiation treatment start to death or censored. DNA samples for genotyping were extracted from buffy-coat which was collected before commencement of treatment. 19 SNPs in 10 genes (BMP1, BMP2, INHBC, SMAD1, SMAD3, SMAD4, SMAD6, SMAD7, SMAD8, TGFβ1), which was reported to have significant correlation with OS of lung cancer, were selected. MassArray System (Sequenom Company) was used for genotyping. Cox regression was performed for multivariate analysis to examine the effects of genotypes on OS using dominant and recessive genetic model. Results: 126 consecutive patients, 91% of them were Caucasian, were recruited in this study. All SNPs call rates were over 90%. Assay reproducibility was over 99% by random double-blinding duplicate or triplicate genotyping. Among clinical factors analyzed, radiation dose was only significant independent factor predicting OS (P=0.001). Genotypic association study showed that 7 SNPs (rs235756, rs11939979, rs12102171, rs6494633, rs12456284, rs12906898 and rs4803455) were significantly associated with OS, adjusted for age, gender, smoking, histology, clinical stage, tumor volume, Karnofsky Performance Status, radiotherapy dose, and chemotherapy. The strongest association was in SMAD3: rs12102171 (P=0.004, HR=2.28, 95%CI, 1.26-4.15). Conclusions: This study partly validated findings from previous studies that genetic variations in the TGFβ pathway are significant predictors of overall survival in NSCLC patients treated with definitive radiotherapy with/without chemotherapy.

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