title: Quantitative evaluation of SPRR3 expression in esophageal squamous cell carcinoma by qPCR and its potential use as a biomarker.
abstract: Esophageal squamous cell carcinoma (ESCC) is highly fatal due to late diagnosis and inefficient treatment. Early disease detection could improve diagnosis and patient survival. Esophageal squamous epithelial cells express SPRR3, a member of the small proline-rich protein family, which is downregulated in ESCC. Therefore, SPRR3 expression may be used as a biomarker to follow the transition from healthy mucosa to ESCC. Both SPRR3 mRNA splice variants, v1 and v2, were evaluated by real time PCR in tumor and histologically normal adjacent tissue biopsies from 84 ESCC patients and 18 healthy controls. SPRR3-v1 was most highly expressed in the esophageal mucosa of healthy subjects, with an increasingly lower expression in the adjacent mucosa of ESCC patients and in tumors, respectively. SPRR3-v2 expression was low in normal mucosa and in tumors but it was higher in the adjacent mucosa of ESCC patients. In addition, we found a significant correlation between a lower SPRR3-v1 and SPRR3-v2 expression and age and alcohol consumption, respectively. SPRR3 protein expression presented a good correlation with SPRR3 mRNA expression. Cut-off points to discriminate between healthy mucosa, tumor and adjacent mucosa were determined with receiver operating characteristic (ROC) curves. This analysis showed that SPRR3-v1 expression discriminates the esophageal mucosa of healthy subjects from the adjacent mucosa and the tumor of ESCC patients with high sensitivity and specificity. Our data shows that the quantitative analysis of SPRR3 mRNA is a robust and reliable method to monitor the malignant transformation of the healthy esophageal mucosa into ESCC.
authors.affiliation: Departamento de Bioquímica, Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto Alcantara Gomes, Rio de Janeiro, Brazil.
authors.forename: Tatiana
authors.initials: T
authors.lastname: de A Simão
authors.forename: Paulo T
authors.initials: PT
authors.lastname: Souza-Santos
authors.forename: Diego S L
authors.initials: DS
authors.lastname: de Oliveira
authors.forename: Vagner
authors.initials: V
authors.lastname: Bernardo
authors.forename: Sheila C S
authors.initials: SC
authors.lastname: Lima
authors.forename: Davy C M
authors.initials: DC
authors.lastname: Rapozo
authors.forename: Cleber D P
authors.initials: CD
authors.lastname: Kruel
authors.forename: Paulo A
authors.initials: PA
authors.lastname: Faria
authors.forename: Luis F
authors.initials: LF
authors.lastname: Ribeiro Pinto
authors.forename: Rodolpho M
authors.initials: RM
authors.lastname: Albano
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D055233:Cornified Envelope Proline-Rich Proteins / Q000235:genetics* / Q000378:metabolism; D003710:Demography; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D055233:Cornified Envelope Proline-Rich Proteins; D012333:RNA, Messenger; C112254:SPRR3 protein, human