Reduced expression of growth and differentiation factor-9 (GDF9) is associated with aggressive behaviour of human clear-cell renal cell carcinoma and poor patient survival.

Growth and differentiation factor-9 (GDF9) is a member of the bone morphogentic protein (BMP) family. GDF9 was recently shown to be a regulator of the development and spread of cancer cells, including kidney cancer cells. However, the clinical implication of GDF9 in human clear-cell renal cell carcinoma (CCRCC) remains unknown. In the present study, the expression of GDF9 in human CCRCC tissues, and correlation between GDF9 and pathological grade and stage of the tumours were examined in CRCC specimens. The expression of GDF9 was examined in paired human normal renal and CCRCC tumour tissues (n=86). The expression of GDF9 in human renal tissues was assessed at both the mRNA and protein levels using reverse transcription-polymerase chain reaction and western blot. Furthermore, the survival curve was constructed using Kaplan-Meier method. Decreased GDF9 protein levels were seen in CCRCC tissues compared with normal tissues. Low protein levels were seen in tumours with high clinical stages and with high pathological nuclear grade of CCRCC. Likewise, levels of GDF9 transcript in normal renal specimens was significantly higher than that in CCRCC tissues. The transcript levels of GDF9 differed significantly amongst different clinical stages and different pathological nuclear grade of CCRCC: The higher the clinical stage or pathological nuclear grade of CCRCC, the lower the transcript level of GDF9. Cumulative survival curves indicated that GDF9 mRNA expression was negatively correlated with cumulative survival time. Patients with high level of GDF9 had significantly longer survival time than the patients with low level of GDF9 (p<0.001). GDF9 expression is markedly decreased in CCRCC, and is linked to pathological grade, clinical stage and long-term survival of the patients. This suggests that GDF9 is a potential tumour suppressor in CCRCC.

Du P ，Ye L ，Yang Y ，Jiang WG ... -  《-》

The differential expression of vascular endothelial growth inhibitor isoforms, VEGI251, VEGI174 and VEGI192 in human clear-cell renal cell carcinoma.

Zhang N ，Wu P ，Wu L ，Shayiremu D ，Shan H ，Ye L ，Jiang WG ，Gong K ，Yang Y ... -  《-》

MicroRNAs with prognostic potential for metastasis in clear cell renal cell carcinoma: a comparison of primary tumors and distant metastases.

Heinzelmann J ，Unrein A ，Wickmann U ，Baumgart S ，Stapf M ，Szendroi A ，Grimm MO ，Gajda MR ，Wunderlich H ，Junker K ... -  《-》

Loss of expression of growth differentiation factor-9 (GDF9) in human kidney cancer and regulation of growth and migration of kidney cancer cells by GDF9.

Du P ，Ye L ，Li H ，Ruge F ，Yang Y ，Jiang WG ... -  《-》

hZIP1 that is down-regulated in clear cell renal cell carcinoma is negatively associated with the malignant potential of the tumor.

The human ZRT, IRT-like protein 1 (hZIP1) has been associated with tumorigenesis. However, its role in clear cell renal cell carcinoma (ccRCC) has not been yet reported. The objective was to investigate hZIP1 expression in ccRCC and its association with clinicopathological features. A total of 106 ccRCC tissue samples and corresponding normal kidney tissue samples were examined, along with 3 ccRCC cell lines (ACHN, 769-P, and 786-O). Real-time polymerase chain reaction, Western blot, and immunohistochemistry were used to investigate the expression of hZIP1 and its relationship with clinicopathological features. The ACHN cell line, exhibiting the highest hZIP1 expression, was transfected with hZIP1 small interfering RNA or mock small interfering RNA. Cellular proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Invasion was determined by Transwell assay. The level of hZIP1 was decreased in ccRCC tissues when compared with normal tissues. hZIP1 expression significantly decreased with increasing clinical stage and pathological grade in ccRCC samples (P<0.05), showing a significant negative correlation with the histological grade (P<0.05). High hZIP1 expression was associated with a better disease-free survival (P<0.01). Silencing of hZIP1 expression enhanced the proliferative and invasive abilities of ACHN cells. Results suggest that hZIP1 may act as a tumor suppressor in ccRCC. hZIP1 is closely correlated with clinicopathological features. High hZIP1 expression may be an indicator of good prognosis in ccRCC.

Dong X ，Kong C ，Zhang Z ，Liu X ，Zhan B ，Chen Z ，Shi D ... -  《-》