Serum TGF-β1 Levels In Patients Research Articles

Abstract 2865: High serum transforming growth factor β1 levels associated with poor survivals in patients with advanced hepatocellular carcinoma

Abstract Background: TGF-β (Transforming growth factor β) signaling pathway plays a significant role in mediating progression, metastasis, and immune evasion of human malignancies. Previous studies have found that serum TGF-β1 levels were elevated in patients with hepatocellular carcinoma (HCC) compared to patients with chronic hepatitis or cirrhosis. However, the prognostic role of serum TGF-β1 levels in patients with advanced HCC is currently unknown. Patients and Methods: We enrolled patients who had received sorafenib or sorafenib-based combination therapy for advanced HCC, defined as metastatic or locally advanced diseases not amenable to loco-regional therapies, at National Taiwan University Hospital, Taipei, Taiwan, between 2007 and 2012. The baseline blood samples were collected before sorafenib treatment with the consent of the patients. Serum TGF-β1 levels were measured by Human TGF-β1 Instant ELISA (eBioscience, Vienna, Austria), and were correlated with disease control rate (DCR), progression- free survival (PFS), and overall survival (OS) of the patients. Results: The study enrolled 91 patients (M:F=82:9), with a median age of 56.9 years. Sixty-nine patients (75.8 %) had chronic hepatitis B virus (HBV) infection, 18 (19.7%) had chronic hepatitis C infection, 82 (90.1%) had Barcelona Clinic Liver Cancer stage C disease, 81(89.0%) had either extrahepatic metastasis or macrovascular invasion, and 88 (96.7%) had Eastern Cooperative Oncology Group performance status of ≤ 1. All patients had Child-Puch class A liver function reserve. Patients with high baseline serum TGF-β1 levels (higher than the median level of the whole patient cohort), compared to patients with low serum TGF-β1 levels, had significantly shorter PFS (median, 2.54 vs. 4.27 months, p = 0.022) and OS (median, 5.57 vs. 11.6 months, p = 0.029). The DCRs for patients with high and low TGF-β1 were not statistically different (54.3 % vs. 62.2%, p = 0.4463). High baseline TGF-β1 levels tended to associate with high serum alpha-fetal protein (AFP) levels and high Cancer of the Liver Italian Program (CLIP) scores, although not reaching statistical significance. Conclusions: High baseline serum TGF-β1 levels were associated with poor PFS and OS in patients with advanced HCC. (This study was supported by grants NRPB-100CAP1020-2, NSC101-2314-B-002-141 & NSC102-2314-B-002 -120). Citation Format: Tzu-Hsuan Lin, Yu-Yun Shao, Soa-Yu Chan, Chung-Yi Huang, Ann-Lii Cheng, Chih-Hung Hsu. High serum transforming growth factor β1 levels associated with poor survivals in patients with advanced hepatocellular carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2865. doi:10.1158/1538-7445.AM2014-2865

Effects of low-level laser therapy on the serum TGF-β1 concentrations in individuals with autoimmune thyroiditis.

The objective of this study was to evaluate the serum concentration of transforming growth factor-β1 (TGF-β1) after low-level laser therapy (LLLT) in patients with hypothyroidism resulting from chronic autoimmune thyroiditis (CAT). Certain data indicate that LLLT is effective in patients with hypothyroidism caused by CAT; however, the mechanisms of action of LLLT in thyroid tissue are unknown. Cytokines could play a role in the response to LLLT. A randomized, placebo-controlled trial included 43 patients with a history of levothyroxine therapy for CAT-induced hypothyroidism. The patients were randomly assigned to receive either 10 sessions of LLLT (830 nm, 50 mW output power, and 707 J/cm(2) fluence; L group, n=23) or 10 sessions of a placebo treatment (P group, n=20) twice a week. Levothyroxine was maintained at the same dose during the entire study period. TGF-β1 was measured both pre-intervention and 30 days post-intervention in both groups. The differences were calculated between the TGF-β1 values observed 30 days post-intervention and the pre-intervention TGF-β1 values for each group (intragroup). Comparing the differences in TGF-β1 levels between the L group (874.9±541.7 pg/mL) and the P group (-128.4±832.8 pg/mL) revealed that there was a statistically significant increase in TGF-β1 levels 30 days post-intervention in group L compared with the placebo group (p=0.0379). This finding suggested that the significant increase in serum TGF-β1 levels in patients with CAT-induced hypothyroidism was associated with the thyroid LLLT procedure. Future studies of the effect of LLLT on TGF-β1 gene expression in thyroid tissue are necessary to confirm these findings.

Expression of Fas/FasL in CD8+ T and CD3+ Foxp3+ Treg cells--relationship with apoptosis of circulating CD8+ T cells in hepatocellular carcinoma patients.

Dysfunction of the host immune system in cancer patients can be due to a number of factors, including lymphocyte apoptosis. Several studies showed that Foxp3+T cells take part in inducing this process by expressing FasL in tumor patients. However, the relationship between apoptosis, CD8+T cells and Foxp3+T cells in HCC patients is still unclear. The present study was designed to investigate the correlation between apoptosis levels and Fas/FasL expression in CD8+T lymphocytes and Foxp3+T cells in patients with HCC. CD8+T cells and CD3+Foxp3+T cells were tested from peripheral blood of HCC patients and normal controls and subjected to multicolor flow cytometry. The expression of an apoptosis marker (annexin V) and the death receptor Fas in CD8+T cells and FasL in CD3+Foxp3+T cells were evaluated. Serum TGF-β1 levels in patients with HCC were measured by enzyme-linked immunosorbent assay. The relationship between apoptosis and Fas expression, as well as FasL expression in CD3+Foxp3+T cells was then evaluated. The frequency of CD8+T cells binding annexin V and Fas expression in CD8+T cells, were all higher in HCC patients than normal controls and the proportion of apoptotic CD8+T cells correlated with their Fas expression. Serum TGF-β1 levels correlated inversely with CD3+Foxp3+T cells. Fas/FasL interactions might lead to excessive turnover of CD8+T cells and reduce anti-tumor immune responses in patients with HCC. Further investigations of apoptosis induction in Fas+CD8+T cells in vitro are required.

Clinical significance of serum transforming growth factor-β1 in lung cancer

Background: Transforming growth factor-β1 (TGF-β1) plays a critical role in human cancer development. Present study aimed to explore the clinical significance of serum TGF-β1 levels in patients with lung cancer and analyze the relationship between TGF-β1 and existing tumor markers for lung cancer. Methods: Serum was collected from 118 patients with lung cancer and 40 healthy volunteers. Serum TGF-β1 levels were measured by enzyme-linked immunosorbent assay (ELISA), and the association with various clinical characteristics was analyzed. The diagnostic value of TGF-β1 was assessed alone and in combination with existing tumor markers for lung cancer. Results: Serum TGF-β1 levels were significantly higher in patients with lung cancer compared to healthy volunteers [0.6×105 (0.4×105, 0.9×105)pg/ml vs 0.5×105 (0.3×105, 0.7×105)pg/ml, P=0.040]. Although there was a positive correlation between serum TGF-β1 levels and advanced stages, the significant difference was not found between early stages and advanced stages (P=0.116). The ability of serum TGF-β1 to discriminate lung cancer at a cutoff value of 79,168pg/ml exhibited sensitivity of 30.6% and specificity of 97.5%. Serum TGF-β1 levels were correlated to cytokeratin fragment 21-1 (CYFRA21-1; R=0.308, P=0.020) and neuron-specific enolase (NSE; R=0.558, P=0.003). The diagnostic accuracy rates for the existing lung-tumor markers, as SCC, CYFRA21-1, and NSE, were increased from 20.0%, 34.6%, and 45.9% to 48.9%, 51.7%, and 54.5%, respectively by the inclusion of serum TGF-β1 levels. Conclusion: Quantification of serum TGF-β1 levels by ELISA may provide a novel complementary tool for the clinical diagnosis of lung cancer.