RGD Reference Report - Inactivation of Smad4 is a prognostic factor in intrahepatic cholangiocarcinoma. - Rat Genome Database

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Inactivation of Smad4 is a prognostic factor in intrahepatic cholangiocarcinoma.

Authors: Yan, Xue-qiang  Zhang, Wei  Zhang, Bi-xiang  Liang, Hui-fang  Zhang, Wan-guang  Chen, Xiao-ping 
Citation: Yan XQ, etal., Chin Med J (Engl). 2013 Aug;126(16):3039-43.
RGD ID: 21066336
Pubmed: PMID:23981608   (View Abstract at PubMed)

BACKGROUND: Smad4 is found mutated in many cancers. It acts as a tumor suppressor in the regulation of TGF-β signaling pathway. The objective of this work was to study the expression of Smad4 in intrahepatic cholangiocarcinoma (ICC) and its relationship with the biological behavior and prognosis of the disease.
METHODS: Forty-nine paraffin-embedded ICC specimens and nine normal liver tissues were analyzed by immunohistochemical methods using Smad4 monoclonal antibodies. The expression of Smad4 was compared with the clinical pathological characteristics of the patients.
RESULTS: The expression of Smad4 was 100% positive in normal liver tissues, which was higher than that in the ICC (44.9%). Negative labeling of the Smad4 protein was found in 26.1% (6/23) of well-differentiated ICCs and 61.5% (16/26) of poorly to moderately differentiated ICCs, and 34.3% (12/35) and 71.4% (10/14) showed negative Smad4 labeling (P = 0.018) of ICC at pathological Tumor Node Metastasis (pTNM) stage I-II and pTNM stage III-IV separately. Furthermore, 72% (8/11) of lymph node metastatic ICCs and 73.3% (11/15) of intrahepatic metastatic ICCs showed negative labeling of the Smad4 protein. The loss of Smad4 expression in those metastatic ICCs was significantly more severe compared with non-metastatic ICCs (P = 0.000).
CONCLUSIONS: The expression of Smad4 was associated with the histological grade, clinical stage, and metastasis of ICC (P < 0.05). The detection of Smad4 may be helpful in determining the degree of malignancy and prognosis of ICC.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SMAD4Humanintrahepatic cholangiocarcinoma disease_progressionIEP  RGD 
Smad4Ratintrahepatic cholangiocarcinoma disease_progressionISOSMAD4 (Homo sapiens) RGD 
Smad4Mouseintrahepatic cholangiocarcinoma disease_progressionISOSMAD4 (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Smad4  (SMAD family member 4)

Genes (Mus musculus)
Smad4  (SMAD family member 4)

Genes (Homo sapiens)
SMAD4  (SMAD family member 4)

Additional Information