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A microRNA-related single nucleotide polymorphism of the XPO5 gene is associated with survival of small cell lung cancer patients.

ABSTRACT: MicroRNA (miRNA)-related single nucleotide polymorphisms (miR-SNPs) in miRNA processing machinery genes affect cancer risk, treatment efficacy and patient prognosis. A miR-SNP of rs11077 located in the 3'UTR of miRNA processing machinery gene XPO5 was examined in small cell lung cancer (SCLC) patients to evaluate its association with cancer survival. A total of 42 patients were enrolled in the present study and genotyped for rs11077 and survival was assessed using the Kaplan-Meier method, as well as univariate and multivariate analyses. The AA genotype of rs11077 was identified for its significant association with better survival time (P=0.023). In addition, rs11077 was found to associate independently with overall survival in SCLC patients by multivariate analysis (relative risk 2.469; 95% CI, 1.088-5.603; P=0.031). The findings of this study suggest that although miR-SNP studies for miRNA processing machinery genes are still at an early age, miR-SNPs have an impact on cancer survival. In conclusion, a miR-SNP in the 3'UTR region of the XPO5 gene was identified as an independent prognostic marker for survival of advanced SCLC patients.

SUBMITTER: Guo Z

PROVIDER: S-EPMC3917003 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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A microRNA-related single nucleotide polymorphism of the <i>XPO5</i> gene is associated with survival of small cell lung cancer patients.

Guo Zhanjun Z Wang Hongjing H Li Yantao Y Li Bin B Li Cuiqiao C Ding Cuimin C

Biomedical reports 20130329 4

MicroRNA (miRNA)-related single nucleotide polymorphisms (miR-SNPs) in miRNA processing machinery genes affect cancer risk, treatment efficacy and patient prognosis. A miR-SNP of rs11077 located in the 3'UTR of miRNA processing machinery gene <i>XPO5</i> was examined in small cell lung cancer (SCLC) patients to evaluate its association with cancer survival. A total of 42 patients were enrolled in the present study and genotyped for rs11077 and survival was assessed using the Kaplan-Meier method, ...[more]

PMID: 24648983

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Project description:Objectives: Platinum-based chemotherapy is first-line treatment for non-small cell lung cancer (NSCLC) patients. The efficacy is limited by drug resistance. Recent studies suggest that ATP7B, a copper efflux transporter, may be involved in platinum resistance. However, the clinical significance of ATP7B expression in NSCLC is controversial. Moreover, the effects of single nucleotide polymorphisms (SNPs) in ATP7B gene on the response to platinum-based chemotherapy are scarcely understood. The aim of our study is to evaluate the clinical value of ATP7B in NSCLC patients and explore the interrelationships between ATP7B SNPs and protein expression, and their association with chemotherapy response. Materials and Methods: A total of 247 NSCLC patients were recruited in this study. Among them, 158 patients who received platinum-based chemotherapy were used to explore the interrelationships between ATP7B SNPs, protein expression and chemotherapy response, while 89 patients who underwent surgical resection were used to further investigate the association between ATP7B SNPs and expression level. We genotyped 15 SNPs of ATP7B by Sequenom MassARRAY and determined ATP7B protein levels by immunohistochemistry. Results: Patients with ATP7B-negative tumors had improved chemotherapeutic response (p=0.025) and better overall survival (p=0.044) compared with the patients with ATP7B-positive tumors. The multivariate Cox regression analysis revealed that ATP7B expression was an independent prognostic factor (HR=0.639, 95%CI=0.424-0.962, p=0.032). Moreover, we found that the rs9526814 GG genotype was significantly associated with favorable response to platinum-based chemotherapy when compared with TT+TG genotypes (OR=0.362, 95CI%=0.140-0.935, p=0.036). Mechanistically, rs9526814 GG genotype showed a strong trend towards reduced expression level of ATP7B compared with the TT+TG genotypes (p= 0.048). Conclusion: Our findings indicate that ATP7B rs9526814 may contribute to platinum resistance by influencing ATP7B gene expression and can be used as a potential biomarker to predict the sensitivity of platinum-based chemotherapy in NSCLC patients.

Project description:BACKGROUND: RECQL is a DNA helicase involved in DNA mismatch repair. The RECQL polymorphism, 3' untranslated region (UTR) A159C, was previously associated with overall survival of patients with resectable pancreatic adenocarcinoma treated with neoadjuvant chemoradiation. In the present study, we examined RECQL for somatic mutations and other polymorphisms and compared these findings with the outcome in patients who received adjuvant or neoadjuvant chemoradiation. We hypothesized that RECQL (i) would be mutated in cancer, (ii) would have polymorphisms linked to the 3'UTR A159C and that either or both events would affect function. We also hypothesized that (iii) these changes would be associated with survival in both cohorts of patients. MATERIAL AND METHODS: We sequenced RECQL's 15 exons and surrounding sequences in paired blood and tumour DNA of 39 patients. The 3'UTR A159C genotype was determined in blood DNA samples from 176 patients with resectable pancreatic adenocarcinoma treated with adjuvant (53) or neoadjuvant (123) chemoradiation. Survival was calculated using the Kaplan-Meier method, with log rank comparisons between groups. The relative impact of genotype on time to overall survival was performed using the Cox proportional hazards model. RESULTS: Somatic mutations were found in UTRs and intronic regions but not in exonic coding regions of the RECQL gene. Two single nucleotide polymorphisms (SNPs), located in introns 2 and 11, were found to be part of the same haplotype block as the RECQL A159C SNP and showed a similar association with overall survival. No short-term difference in survival between treatment strategies was found. We identified a subgroup of patients responsive to neoadjuvant therapy in which the 159 A allele conferred strikingly improved long-term survival. DISCUSSION: The RECQL 3'UTR A159C SNP is not linked with other functional SNPs within RECQL but may function as a site for regulatory molecules. The mechanism of action needs to be clarified further.

Dataset Information

A microRNA-related single nucleotide polymorphism of the XPO5 gene is associated with survival of small cell lung cancer patients.

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A microRNA-related single nucleotide polymorphism of the <i>XPO5</i> gene is associated with survival of small cell lung cancer patients.

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