title: L-DOPA decarboxylase mRNA levels provide high diagnostic accuracy and discrimination between clear cell and non-clear cell subtypes in renal cell carcinoma.
abstract: OBJECTIVE
  Renal cell carcinoma (RCC) is the most frequent type of kidney cancer. RCC patients frequently present with arterial hypertension due to various causes, including intrarenal dopamine deficiency. L-DOPA decarboxylase (DDC) is the gene encoding the enzyme that catalyzes the biosynthesis of dopamine in humans. Several studies have shown that the expression levels of DDC are significantly deregulated in cancer. Thus, we herein sought to analyze the mRNA levels of DDC and evaluate their clinical significance in RCC.
  
  
  METHODS
  DDC levels were analyzed in 58 surgically resected RCC tumors and 44 adjacent non-cancerous renal tissue specimens via real-time PCR. Relative levels of DDC were estimated by applying the 2(-ΔΔC)T method, while their diagnostic accuracy and correlation with the clinicopathological features of RCC tumors were assessed by comprehensive statistical analysis.
  
  
  RESULTS
  DDC mRNA levels were found to be dramatically downregulated (p<0.001) in RCC tumors, exhibiting remarkable diagnostic accuracy as assessed by ROC curve analysis (AUC: 0.910; p<0.001) and logistic regression (OR: 0.678; p=0.001). Likewise, DDC was found to be differentially expressed between clear cell RCC and the group of non-clear cell subtypes (p=0.001) consisted of papillary and chromophobe RCC specimens. Furthermore, a statistically significant inverse correlation was also observed when the mRNA levels of DDC were analyzed in relation to tumor grade (p=0.049).
  
  
  CONCLUSIONS
  Our data showed that DDC constitutes a highly promising molecular marker for RCC, exhibiting remarkable diagnostic accuracy and potential to discriminate between clear cell and non-clear cell histological subtypes of RCC.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Panepistimiopolis, 15701 Athens, Greece.
authors.forename: Emmanuel I
authors.initials: EI
authors.lastname: Papadopoulos
authors.affiliation: Department of Pathology, "Metropolitan" General Hospital, Neo Faliro, 18547 Athens, Greece.
authors.forename: Constantina
authors.initials: C
authors.lastname: Petraki
authors.affiliation: Department of Urology, "Evangelismos" General Hospital, 10676 Athens, Greece.
authors.forename: Alkiviadis
authors.initials: A
authors.lastname: Gregorakis
authors.affiliation: Department of Pathology, "Metropolitan" General Hospital, Neo Faliro, 18547 Athens, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Chra
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Panepistimiopolis, 15701 Athens, Greece.
authors.forename: Emmanuel G
authors.initials: EG
authors.lastname: Fragoulis
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Panepistimiopolis, 15701 Athens, Greece. Electronic address: ascorilas@biol.uoa.gr.
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D001142:Aromatic-L-Amino-Acid Decarboxylases; C000595218:DDC protein, human
keywords: L-DOPA decarboxylase; Molecular marker; Real-time PCR; Renal cell carcinoma