RGD Reference Report - Up-regulation of Tiam1 and Rac1 correlates with poor prognosis in hepatocellular carcinoma. - Rat Genome Database

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Up-regulation of Tiam1 and Rac1 correlates with poor prognosis in hepatocellular carcinoma.

Authors: Yang, Wanyong  Lv, Shemin  Liu, Xingyan  Liu, Hong  Yang, Wen  Hu, Fu 
Citation: Yang W, etal., Jpn J Clin Oncol. 2010 Nov;40(11):1053-9. doi: 10.1093/jjco/hyq086. Epub 2010 Jun 3.
RGD ID: 153350129
Pubmed: PMID:20522449   (View Abstract at PubMed)
DOI: DOI:10.1093/jjco/hyq086   (Journal Full-text)


OBJECTIVE: T-cell lymphoma invasion and metastasis 1 (Tiam1) specifically activates Rho-like GTPases (e.g. Rac1) and Tiam1-Rac1 pathway affects the migration and invasion of many tumors, such as nasopharyngeal carcinoma, breast cancer and retinoblastoma. However, no studies have yet comprehensively examined the involvement of Tiam1-Rac1 pathway in hepatocellular carcinoma. In this study, we examined the relationship of the up-regulation of Tiam1 and Rac1 with clinicopathological features in patients with hepatocellular carcinoma.
METHODS: Expression of Tiam1 and Rac1 was assessed in 242 hepatocellular carcinoma tissues and their adjacent normal hepatic tissues by performing immunohistochemistry and was gauged regarding stage, grade and survival.
RESULTS: Immunohistochemistry showed that patients with a high clinical stage hepatocellular carcinoma (III-IV) and α-fetoprotein levels had a higher tendency to express Tiam1 and Rac1 on tumor cells than the patients with low pathologic grade hepatocellular carcinoma (I-II) (P = 0.008 and 0.01, respectively) and low α-fetoprotein levels (P = 0.006 and 0.002, respectively). In addition, Tiam1 and Rac1 up-regulation was also significantly associated with vascular invasion status (both P = 0.02), intrahepatic metastasis status (P = 0.009 and 0.01, respectively) and histological differentiation (P = 0.008 and 0.009, respectively) of patients with hepatocellular carcinoma. Moreover, post-operative survival analysis indicated that hepatocellular carcinoma patients with strong Tiam1 (P = 0.01) and Rac1 (P = 0.02) expression had shorter disease-specific survival than those with weak expression. Multivariate analysis also showed that Tiam1 and Rac1 overexpression could be two predictors of poor prognosis (P = 0.02 and 0.03, respectively).
CONCLUSIONS: The current study demonstrated for the first time that the Tiam1-Rac1 pathway may play a critical role in tumor progression of hepatocellular carcinoma. The expression of Tiam1 and Rac1 can be considered as the two useful indicators for predicting the prognosis of hepatocellular carcinoma.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RAC1Humanhepatocellular carcinoma exacerbatesIEP protein:increased expression:liver (human)RGD 
Rac1Rathepatocellular carcinoma exacerbatesISORAC1 (Homo sapiens)protein:increased expression:liver (human)RGD 
Rac1Mousehepatocellular carcinoma exacerbatesISORAC1 (Homo sapiens)protein:increased expression:liver (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Rac1  (Rac family small GTPase 1)

Genes (Mus musculus)
Rac1  (Rac family small GTPase 1)

Genes (Homo sapiens)
RAC1  (Rac family small GTPase 1)


Additional Information