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The Prognostic Role of SOCS3 and A20 in Human Cholangiocarcinoma.

Wang Y, Wan M, Zhou Q, Wang H, Wang Z, Zhong X, Zhang L, Tai S, Cui Y - PLoS ONE (2015)

Bottom Line: Although tumor necrosis factor α-induced protein 3 (TNFAIP3, also known as A20) can decrease SOCS3 expression and is involved in the regulation of tumorigenesis in certain malignancies, its role in CCA remains unknown.These proteins were both associated with CCA lymph node metastasis, postoperative recurrence and overall survival rate.Thus, our study demonstrated that SOCS3 and A20 represent novel prognostic factors for human CCA.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, P. R. China; Key Laboratory of Myocardial Ischemia Mechanism and Treatment Ministry of Education, Harbin, Heilongjiang, P. R. China.

ABSTRACT
As an antagonist of the JAK/STAT pathway, suppressor of cytokine signaling 3 (SOCS3) plays an integral role in shaping the inflammatory environment, tumorigenesis and disease progression in cholangiocarcinoma (CCA); however, its prognostic significance remains unclear. Although tumor necrosis factor α-induced protein 3 (TNFAIP3, also known as A20) can decrease SOCS3 expression and is involved in the regulation of tumorigenesis in certain malignancies, its role in CCA remains unknown. In this study, we investigated the expression of SOCS3 and A20 in human CCA tissues to assess the prognostic significance of these proteins. The expression of SOCS3 and A20 was initially detected by western blot in 22 cases of freshly frozen CCA tumors with corresponding peritumoral tissues and 22 control normal bile duct tissues. Then, these proteins were investigated in 86 CCA patients by immunohistochemistry (IHC) and were evaluated for their association with clinicopathological parameters in human CCA. The results indicated that SOCS3 expression was significantly lower in CCA tumor tissues than in corresponding peritumoral biliary tissues and normal bile duct tissues. Conversely, A20 was overexpressed in CCA tissues. Thus, an inverse correlation between the expression of SOCS3 and A20 was discovered. Furthermore, patients with low SOCS3 expression or high A20 expression showed a dramatically lower overall survival rate. These proteins were both associated with CCA lymph node metastasis, postoperative recurrence and overall survival rate. However, only A20 showed a significant association with the tumor node metastasis (TNM) stage, while SOCS3 showed a significant association with tumor differentiation. Multivariate Cox analysis revealed that SOCS3 and A20 were independent prognostic indicators for overall survival in CCA. Thus, our study demonstrated that SOCS3 and A20 represent novel prognostic factors for human CCA.

No MeSH data available.


Related in: MedlinePlus

IHC staining for SOCS3 and A20 in human CCA.Original magnification 200×, scale bar = 100 μm. A. High SOCS3 expression was found predominately in the cytoplasm and cytomembrane in CCA tissues. B. Low SOCS3 expression in CCA tissues. C. High A20 expression was found in the nucleus. D. Low A20 expression in CCA tissues.
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pone.0141165.g002: IHC staining for SOCS3 and A20 in human CCA.Original magnification 200×, scale bar = 100 μm. A. High SOCS3 expression was found predominately in the cytoplasm and cytomembrane in CCA tissues. B. Low SOCS3 expression in CCA tissues. C. High A20 expression was found in the nucleus. D. Low A20 expression in CCA tissues.

Mentions: Next, the expression levels of SOCS3 and A20 were detected in tissue slides from 86 CCA cases by IHC. As mentioned above, SOCS3 expression was found predominately in the cytoplasm and cytomembrane, while A20 expression was detected in the nucleus (Fig 2, scale bar = 100 μm). According to the assessment criteria in this study, 62 (72.1%) of the 86 CCA specimens were classified as showing low expression for SOCS3, whereas 24 (27.9%) showed high expression. Conversely, for A20, 27 (31.4%) of the CCA specimens showed low expression, and 59 (69.6%) showed high expression. Consistent with the western blot analysis, the IHC results indicated decreased expression of SOCS3 and increased expression of A20 in CCA.


The Prognostic Role of SOCS3 and A20 in Human Cholangiocarcinoma.

Wang Y, Wan M, Zhou Q, Wang H, Wang Z, Zhong X, Zhang L, Tai S, Cui Y - PLoS ONE (2015)

IHC staining for SOCS3 and A20 in human CCA.Original magnification 200×, scale bar = 100 μm. A. High SOCS3 expression was found predominately in the cytoplasm and cytomembrane in CCA tissues. B. Low SOCS3 expression in CCA tissues. C. High A20 expression was found in the nucleus. D. Low A20 expression in CCA tissues.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4612779&req=5

pone.0141165.g002: IHC staining for SOCS3 and A20 in human CCA.Original magnification 200×, scale bar = 100 μm. A. High SOCS3 expression was found predominately in the cytoplasm and cytomembrane in CCA tissues. B. Low SOCS3 expression in CCA tissues. C. High A20 expression was found in the nucleus. D. Low A20 expression in CCA tissues.
Mentions: Next, the expression levels of SOCS3 and A20 were detected in tissue slides from 86 CCA cases by IHC. As mentioned above, SOCS3 expression was found predominately in the cytoplasm and cytomembrane, while A20 expression was detected in the nucleus (Fig 2, scale bar = 100 μm). According to the assessment criteria in this study, 62 (72.1%) of the 86 CCA specimens were classified as showing low expression for SOCS3, whereas 24 (27.9%) showed high expression. Conversely, for A20, 27 (31.4%) of the CCA specimens showed low expression, and 59 (69.6%) showed high expression. Consistent with the western blot analysis, the IHC results indicated decreased expression of SOCS3 and increased expression of A20 in CCA.

Bottom Line: Although tumor necrosis factor α-induced protein 3 (TNFAIP3, also known as A20) can decrease SOCS3 expression and is involved in the regulation of tumorigenesis in certain malignancies, its role in CCA remains unknown.These proteins were both associated with CCA lymph node metastasis, postoperative recurrence and overall survival rate.Thus, our study demonstrated that SOCS3 and A20 represent novel prognostic factors for human CCA.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, P. R. China; Key Laboratory of Myocardial Ischemia Mechanism and Treatment Ministry of Education, Harbin, Heilongjiang, P. R. China.

ABSTRACT
As an antagonist of the JAK/STAT pathway, suppressor of cytokine signaling 3 (SOCS3) plays an integral role in shaping the inflammatory environment, tumorigenesis and disease progression in cholangiocarcinoma (CCA); however, its prognostic significance remains unclear. Although tumor necrosis factor α-induced protein 3 (TNFAIP3, also known as A20) can decrease SOCS3 expression and is involved in the regulation of tumorigenesis in certain malignancies, its role in CCA remains unknown. In this study, we investigated the expression of SOCS3 and A20 in human CCA tissues to assess the prognostic significance of these proteins. The expression of SOCS3 and A20 was initially detected by western blot in 22 cases of freshly frozen CCA tumors with corresponding peritumoral tissues and 22 control normal bile duct tissues. Then, these proteins were investigated in 86 CCA patients by immunohistochemistry (IHC) and were evaluated for their association with clinicopathological parameters in human CCA. The results indicated that SOCS3 expression was significantly lower in CCA tumor tissues than in corresponding peritumoral biliary tissues and normal bile duct tissues. Conversely, A20 was overexpressed in CCA tissues. Thus, an inverse correlation between the expression of SOCS3 and A20 was discovered. Furthermore, patients with low SOCS3 expression or high A20 expression showed a dramatically lower overall survival rate. These proteins were both associated with CCA lymph node metastasis, postoperative recurrence and overall survival rate. However, only A20 showed a significant association with the tumor node metastasis (TNM) stage, while SOCS3 showed a significant association with tumor differentiation. Multivariate Cox analysis revealed that SOCS3 and A20 were independent prognostic indicators for overall survival in CCA. Thus, our study demonstrated that SOCS3 and A20 represent novel prognostic factors for human CCA.

No MeSH data available.


Related in: MedlinePlus