RESUMO
BACKGROUND/PURPOSE: Inflammation plays an important role in promoting ovarian tumorigenesis and cancer progression. However, the relationship between polymorphisms in inflammatory response genes and risk of ovarian cancer remains poorly understood. In this study, we investigated the association of PPARG Pro12Ala, IL6-174G/C, E-selectin S128R, NFKB1-94 ins/del, NFKBIA-826C/T, and ICAM-1 K469E polymorphisms with ovarian cancer risk in a Chinese population. METHODS: Genotyping of the polymorphisms was performed on 687 cases and 687 controls employing the PCR-RFLP technique, and the logistic regression model was used to measure the risk association. RESULTS: A significantly increased risk association was observed for the heterozygous genotypes of PPARG [odds ratio (OR) = 1.52, 95% confidence interval (CI) = 1.01-2.29] and E-selectin (OR = 1.77, 95% CI = 1.07-2.93) polymorphisms, as well as the homozygous ins/ins genotype of NFKB1 polymorphism (OR = 1.39, 95% CI = 1.00-1.92). By contrast, ICAM-1 KE genotype was associated with a decreased ovarian cancer risk (OR = 0.77, 95% CI = 0.60-0.98). In addition, the NFKB1 del/del + NFKBIA TT combination was also found to be associated with a decreased ovarian cancer risk, with OR = 0.12 (95% CI = 0.01-0.95). The associations of the NFKB1 and ICAM-1 polymorphisms replicated the findings of previous reports, assuring the reliability of the results obtained. CONCLUSION: NFKB1 and ICAM-1 polymorphisms could serve as useful ovarian cancer risk prediction biomarkers for the Chinese population, while the utility of PPARG and E-selectin polymorphisms as biomarkers requires further confirmation in independent ovarian cancer cohorts.
Assuntos
Biomarcadores , Neoplasias Ovarianas/genética , Polimorfismo de Nucleotídeo Único , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , China , Selectina E/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Proteínas I-kappa B/genética , Molécula 1 de Adesão Intercelular/genética , Interleucina-6/genética , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Inibidor de NF-kappaB alfa , Subunidade p50 de NF-kappa B/genética , PPAR gama/genética , Reprodutibilidade dos TestesRESUMO
The proteasome has been validated as an anticancer drug target, while the role of a subunit of proteasome, PSMC6, in lung adenocarcinoma (LUAD) has not been fully unveiled. In this study, we observed that both the RNA and protein of PSMC6 were highly upregulated in LUAD compared with the adjacent normal tissues. Moreover, a high PSMC6 expression was associated with poor prognosis. In accordance with this finding, PSMC6 was associated with poor tumor differentiation. Furthermore, the silence of PSMC6 by small interference RNAs (siRNAs) could significantly inhibit cell growth, migration, and invasion in lung cancer cell lines, suggesting that PSMC6 might serve as a promising therapeutic target in LUAD. To further explore the molecular mechanism of PSMC6 in LUAD, we observed that the proteasome subunits, such as PSMD10, PSMD6, PSMD9, PSMD13, PSMB3, PSMB1, PSMA4, PSMC1, PSMC2, PSMD7, and PSMD14, were highly correlated with PSMC6 expression. Based on the gene set enrichment analysis, we observed that these proteasome subunits were involved in the degradation of AXIN protein. The correlation analysis revealed that the positively correlated genes with PSMC6 were highly enriched in WNT signaling-related pathways, demonstrating that the PSMC6 overexpression may activate WNT signaling via degrading the AXIN protein, thereby promoting tumor progression. In summary, we systematically evaluated the differential expression levels and prognostic values of PSMC6 and predicted its biological function in LUAD, which suggested that PSMC6 might act as a promising therapeutic target in LUAD.