RhoA is associated with invasion and lymph node metastasis in upper urinary tract cancer

Abstract

OBJECTIVE To assess the roles of RhoA small GTPase (RhoA) in upper urinary tract cancer by analysing the mRNA and protein levels of RhoA. PATIENTS AND METHODS The mRNA and protein levels of RhoA in matched sets of tumour, non‐tumour and metastatic lymph node tissues of surgical specimens were analysed in 47 consecutive patients with renal pelvic/ureteric cancer, using the polymerase chain reaction after reverse transcription and Western blotting. The relationship between mRNA and protein levels of RhoA in tumour tissues and the clinicopathological features of the patients was also assessed. RESULTS The mRNA levels of RhoA and RhoA protein were greater in tumour and metastatic lymph node tissues than in non‐tumour tissues (all P < 0.001). The expression levels of RhoA mRNA and protein levels in primary tumours was related to poorly differentiated grade (both P < 0.05) and muscle invasion (P < 0.01 and < 0.001, respectively). Kaplan‐Meier plots of survival in patients with low or high RhoA showed that high mRNA and protein levels were associated with a shorter disease‐free (P < 0.01) and overall survival (P < 0.001). Multivariate analysis using the Cox proportional hazards model showed that a high RhoA protein level was an independent prognostic factor, second to stage, in disease‐free and overall survival (both P < 0.05). CONCLUSIONS These findings suggest that RhoA is involved in the invasion and metastasis of upper urinary tract cancer, indicating that RhoA may be a useful prognostic factor in this disease.

A Definitive Role of RhoC in Metastasis of Orthotopic Lung Cancer in Mice

“…Likewise, there is a possibility that a specific type of Rho isoform may be involved in the pathogenesis of lung cancer. In clinical studies, significant increases in RhoA in head and neck squamous cell (27), upper urinary tract (28), colon (29), breast (29), and lung (29) cancer and significant increases in RhoC in breast cancer (13,14,30) were shown, although other Rho isoforms were not investigated in these studies. Thus far, only four studies, to our knowledge, have compared the combined expression levels of RhoA, RhoB, and RhoC in cancer of human patients.…”

Reversal of the Malignant Phenotype of Gastric Cancer Cells by Inhibition of RhoA Expression and Activity

“…We show that the expression level of RhoA protein is significantly higher in gastric cancer tissues and cells than that in normal gastric mucosae or immortal gastric epithelial cells by immunohistochemical examination and Western blotting analysis. In a number of previous reports, it was shown that RhoA was involved in progression of testicular germ cell, upper urinary tract, bladder, and ovarian cancer (11)(12)(13)26), suggesting that RhoA might be a useful prognostic factor in these diseases. We found that RhoA expression was not associated with the differentiation grade, Tumor-Node-Metastasis stage, gross type or metastasis, suggesting that although up-regulation of RhoA may be associated with gastric cancer properties, the expression level of RhoA does not correlate with the progressiveness of the disease.…”

Overexpression of RhoA, Rac1, and Cdc42 GTPases Is Associated with Progression in Testicular Cancer

“…Postoperative follow-up ranged from 3 to 60 months (median follow-up, 29 months). In all cases, three sites of tumor and varying portions of adjacent nonneoplastic testis were examined for the study (10,11). Clinical staging was carried out according to the criteria of Tumor-Node-Metastasis classification (19).…”