Gene expression analysis of renal carcinoma: adipose differentiation-related protein as a potential diagnostic and prognostic biomarker for clear-cell renal carcinoma.
The gene expression profiles of 33 renal cell carcinomas (RCCs) and nine normal kidney samples were examined using high-density oligonucleotide microarrays in an attempt to identify biomolecular markers for the diagnosis of tumour subtypes and also for prediction of prognosis. Hierarchical clustering demonstrated that clear-cell RCC, chromophobe RCC, and normal kidney tissue showed distinctive gene expression profiles. The mean expression levels of 149 of 12 500 genes were more than three times higher in clear-cell RCC than in chromophobe RCC and normal kidney tissue. Among the genes whose expression was upregulated in clear-cell RCC, adipose differentiation-related protein (ADFP) and nicotinamide N-methyltransferase (NNMT) were selected for further analysis. Consistent with the results of the microarray, increased levels of ADFP and NNMT mRNA were found more frequently in clear-cell RCCs than in other non-clear-cell tumour subtypes using real-time quantitative PCR. Immunohistochemistry for ADFP showed strong and unique tumour cell staining patterns in the majority of clear-cell RCCs. More importantly, patients bearing tumours with higher AFDP mRNA levels showed significantly better survival in both univariate and multivariate analyses. ADFP is a lipid storage droplet-associated protein and its transcription is considered to be regulated by the von Hippel-Lindau/hypoxia-inducible factor pathway. It is known that clear-cell RCC contains abundant lipids and cholesterols. Thus it is likely that sustained upregulation of ADFP following VHL inactivation is involved in the morphological appearance of clear-cell RCC. Moreover ADFP expression status may provide useful prognostic information as a biomolecular marker in patients with clear-cell RCC.
Yao
Masahiro
M
Department of Urology and Molecular Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan. masayao@med.yokohama-cu.ac.jp
Tabuchi
Hisahiro
H
Nagashima
Yoji
Y
Baba
Masaya
M
Nakaigawa
Noboru
N
Ishiguro
Hitoshi
H
Hamada
Kenji
K
Inayama
Yoshiaki
Y
Kishida
Takeshi
T
Hattori
Keiko
K
Yamada-Okabe
Hisafumi
H
Kubota
Yoshinobu
Y
D018262:Adenocarcinoma, Clear Cell / Q000175:diagnosis* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000473:pathology; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D000070780:Perilipin-2; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016019:Survival Analysis; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C000602982:PLIN2 protein, human; D000070780:Perilipin-2; D012333:RNA, Messenger; D012334:RNA, Neoplasm