title: A dual role for KRT81: a miR-SNP associated with recurrence in non-small-cell lung cancer and a novel marker of squamous cell lung carcinoma.
abstract: MicroRNAs (miRNAs) play an important role in carcinogenesis through the regulation of their target genes. miRNA-related single nucleotide polymorphisms (miR-SNPs) can affect miRNA biogenesis and target sites and can alter microRNA expression and functions. We examined 11 miR-SNPs, including 5 in microRNA genes, 3 in microRNA binding sites and 3 in microRNA-processing machinery components, and evaluated time to recurrence (TTR) according to miR-SNP genotypes in 175 surgically resected non-small-cell lung cancer (NSCLC) patients. Significant differences in TTR were found according to KRT81 rs3660 (median TTR: 20.3 months for the CC genotype versus 86.8 months for the CG or GG genotype; P = 0.003) and XPO5 rs11077 (median TTR: 24.7 months for the AA genotype versus 73.1 months for the AC or CC genotypes; P = 0.029). Moreover, when patients were divided according to stage, these differences were maintained for stage I patients (P = 0.002 for KRT81 rs3660; P<0.001 for XPO5 rs11077). When patients were divided into sub-groups according to histology, the effect of the KRT81 rs3660 genotype on TTR was significant in patients with squamous cell carcinoma (P = 0.004) but not in those with adenocarcinoma. In the multivariate analyses, the KRT81 rs3660 CC genotype (OR = 1.8; P = 0.023) and the XPO5 rs11077 AA genotype (OR = 1.77; P = 0.026) emerged as independent variables influencing TTR. Immunohistochemical analyses in 80 lung specimens showed that 95% of squamous cell carcinomas were positive for KRT81, compared to only 19% of adenocarcinomas (P<0.0001). In conclusion, miR-SNPs are a novel class of SNPs that can add useful prognostic information on the clinical outcome of resected NSCLC patients and may be a potential key tool for selecting high-risk stage I patients. Moreover, KRT81 has emerged as a promising immunohistochemical marker for the identification of squamous cell lung carcinoma.
authors.affiliation: Department of Medical Oncology, Institut Clinic Malalties Hemato-Oncològiques (ICMHO), Hospital Clinic de Barcelona, University of Barcelona, Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Campayo
authors.forename: Alfons
authors.initials: A
authors.lastname: Navarro
authors.forename: Nuria
authors.initials: N
authors.lastname: Viñolas
authors.forename: Rut
authors.initials: R
authors.lastname: Tejero
authors.forename: Carmen
authors.initials: C
authors.lastname: Muñoz
authors.forename: Tania
authors.initials: T
authors.lastname: Diaz
authors.forename: Ramon
authors.initials: R
authors.lastname: Marrades
authors.forename: Maria L
authors.initials: ML
authors.lastname: Cabanas
authors.forename: Josep M
authors.initials: JM
authors.lastname: Gimferrer
authors.forename: Pere
authors.initials: P
authors.lastname: Gascon
authors.forename: Jose
authors.initials: J
authors.lastname: Ramirez
authors.forename: Mariano
authors.initials: M
authors.lastname: Monzo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001665:Binding Sites; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D016022:Case-Control Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053564:Keratins, Hair-Specific / Q000235:genetics* / Q000378:metabolism; D053531:Keratins, Type II / Q000235:genetics* / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012008:Recurrence; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; C507600:KRT81 protein, human; D053564:Keratins, Hair-Specific; D053531:Keratins, Type II; D035683:MicroRNAs