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Genetic polymorphisms of long non-coding RNA GAS5 predict platinum-based concurrent chemoradiotherapy response in nasopharyngeal carcinoma patients.

ABSTRACT: LncRNA GAS5 plays a tumor suppressive role in a variety of human cancers and promises to be a novel diagnostic biomarker, therapy target, as well as prognostic biomarker. However, the role of GAS5 in nasopharyngeal carcinoma (NPC) remains elusive. The objective of the present study was to evaluate the effect of single nucleotide polymorphisms (SNPs) in GAS5 on treatment efficacy and toxicity in NPC patients receiving chemoradiotherapy. Three potentially functional SNPs of GAS5 were genotyped in 267 NPC patients and validated in another 238 NPC patients treated with chemoradiotherapy from southern China. Multivariate logistic regression analyses and stratification analyses were used to estimate the association of candidate SNPs and chemoradiotherapy efficacy and toxic reactions. Our results showed that rs2067079 kept a consistent association with severe myelosuppression and severe neutropenia in discovery set (OR=2.403, P=0.009; OR=2.454, P=0.015; respectively), validation set (OR=3.653, P=0.027; OR=4.767, P=0.016; respectively), and combined dataset (OR=1.880, P=0.007; OR=2.079, P=0.005; respectively). rs2067079 CT genotype carriers presented an even more remarkable increased risk of severe myelosuppression (OR=3.878, P=0.003) and severe neutropenia (OR=3.794, P=0.009) in subgroups taking paclitaxel+platinum as concurrent chemoradiotherapy regimen. Besides, we found a gene-does effect of rs6790, with the incidence rate of severe myelosuppression decreased from 23.56% to 17.21% to 10% and the incidence rate of severe neutropenia decreased from 30.4% to 20.9% to 17.1% for rs6790 GG vs GA vs AA genotype carriers. Our results indicate the potential role of lncRNA GAS5 polymorphisms rs2067079 and rs6790 as predictive biomarkers for chemoradiotherapy induced toxic reactions in NPC patients.

SUBMITTER: Guo Z

PROVIDER: S-EPMC5617505 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Genetic polymorphisms of long non-coding RNA GAS5 predict platinum-based concurrent chemoradiotherapy response in nasopharyngeal carcinoma patients.

Guo Zhen Z Wang Youhong Y Zhao Yu Y Jin Yi Y An Liang L Wu Bin B Liu Zhaoqian Z Chen Xiaoping X Zhou Honghao H Wang Hui H Zhang Wei W

Oncotarget 20170731 37

LncRNA GAS5 plays a tumor suppressive role in a variety of human cancers and promises to be a novel diagnostic biomarker, therapy target, as well as prognostic biomarker. However, the role of GAS5 in nasopharyngeal carcinoma (NPC) remains elusive. The objective of the present study was to evaluate the effect of single nucleotide polymorphisms (SNPs) in GAS5 on treatment efficacy and toxicity in NPC patients receiving chemoradiotherapy. Three potentially functional SNPs of <i ...[more]

PMID: 28977945

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Project description:BackgroundThe present study aimed to construct a prognostic nomogram including Epstein-Barr virus DNA (EBV-DNA) and sarcopenia in patients with nasopharyngeal carcinoma (NPC) receiving concurrent chemoradiotherapy (CCRT).MethodsIn this retrospective analysis, we studied 1,045 patients with NPC who had been treated with CCRT between 2010 and 2014. Sarcopenia was determined using routine pre-radiotherapy computed tomography scans of the third cervical vertebrae. A new S-E grade was constructed using a receiver-operating characteristic (ROC) curve analyses determined cutoff values of sarcopenia and plasma EBV-DNA. The nomogram was developed base on the sarcopenia-EBV (S-E) grade and traditional prognostic factors. A calibration curve, time-dependent ROC, decision curve analysis, and the concordance index (C-index) determined the accuracy of prediction and discrimination of the nomogram, and were compared with TNM staging system and a traditional nomogram.ResultsPatient survival was significantly different when sarcopenia (P < 0.001) or EBV-DNA (P = 0.001) were used and they continued to be independent prognostic factors for survival upon univariate (P < 0.001, P = 0.002, respectively) and multivariate (P < 0.001, P = 0.015, respectively) analyses. Predicting overall survival (OS) was more accurate using the S-E grade than using TNM staging and sarcopenia or EBV-DNA alone. Nomogram B (model with sarcopenia) or nomogram A (model without sarcopenia) were then developed based on the identified independent prognostic factors. Comparing nomogram prediction with actual observation showed good agreement among the calibration curves for probability of 1-, 3-, and 5-year OS. Predicted survival (C-index = 0.77) of nomogram B was statistically higher than that of nomogram A (0.676, P = 0.020) and TNM staging (0.604, P < 0.001). Risk group stratification could distinguish between survival curves within respective TNM stages (all stages, P < 0.001; stage III, P < 0.001; stage IV, P = 0.002).ConclusionsThe sarcopenia-EBV DNA nomogram allowed more accurate prediction of prognosis for patients with NPC receiving CCRT.

Project description:BackgroundN-stage is related to distant metastasis in nasopharyngeal carcinoma (NPC) patients. The purpose of this study was to evaluate the efficacy and toxicity of different nedaplatin-based chemotherapy regimens in advanced N2-3 stage NPC patients treated with intensity modulated radiation therapy (IMRT).Patients and methodsBetween April 2005 and December 2009, a total of 128 patients with N2-3 advanced NPC were retrospectively analyzed. Patients were treated with IMRT concurrent with 2 cycles of chemotherapy consisting of either nedaplatin plus paclitaxel (NP group, n = 67) or nedaplatin plus fluorouracil and paclitaxel (NFP group, n = 61). Two to four cycles of adjuvant chemotherapy were then administered every 21 days following concurrent chemoradiotherapy.ResultsWith a median follow-up of 60 months, the 5-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) for all patients were 81.4%, 71.5%, 87.8% and 82.0%, respectively. No significant difference in PFS (66.6% vs. 76.7%, P = 0.212) and LRRFS rates (89.0% vs. 86.3%, P = 0.664) was observed between the NP and NFP groups. The 5-year OS (75.4% vs. 88.5%, P = 0.046) and DMFS (75.1% vs. 89.0%, P = 0.042) rate were superior in the NFP group compared with the NP group. The NFP group had a higher incidence of grade 3-4 acute toxicities including bone marrow suppression (leukopenia: ?2 = 3.935, P = 0.047; anemia: ?2 = 9.760, P = 0.002; thrombocytopenia: ?2 = 8.821, P = 0.003), and both liver and renal dysfunction (?2 = 5.206, P = 0.023) compared with the NP group. Late toxicities were moderate and no difference was observed between the two groups.ConclusionIMRT concurrent with nedaplatin-based chemotherapy is an advocated regimen for patients with advanced N2-3 stage NPC. Patients with advanced N2-3 stage may be better candidates for the NFP regimen although this regimen was associated with a high acute toxicity rate.

Project description:PurposeInduction chemotherapy plus concurrent chemoradiotherapy and concurrent chemoradiotherapy alone are both standard treatment regimens for managing locally advanced nasopharyngeal carcinoma. However, the results of comparisons between them in clinical trials vary. Therefore, we designed this meta-analysis to illustrate their advantages and disadvantages in patients with locally advanced nasopharyngeal carcinoma.MethodsWe thoroughly searched the PubMed, EMBASE, and Cochrane Library databases and then merged the effect indicators of hazard ratios and risk ratios using RevMan 5.1.ResultsSeven randomized controlled trials totaling 2,319 patients were included in our research. The synthesized results showed that induction chemotherapy plus concurrent chemoradiotherapy improved overall survival (HR = 0.75, 95% CI: 0.63-0.89, P = 0.001), progression-free survival (HR = 0.69, 95% CI: 0.60-0.80, P < 0.001), distant metastasis-free survival (HR = 0.65, 95% CI: 0.53-0.80, P < 0.001) and locoregional recurrence-free survival (HR = 0.68 95%, CI: 0.54-0.86, P = 0.001) versus concurrent chemoradiotherapy alone. It also increased the risk of anemia, thrombocytopenia, and neutropenia during concurrent chemoradiotherapy. However, the incidence of leukopenia and mucositis was similar in induction chemotherapy and induction chemotherapy plus concurrent chemoradiotherapy. Furthermore, the subgroup analysis showed better survival outcomes with induction chemotherapy plus concurrent chemoradiotherapy than with concurrent chemoradiotherapy alone in the triweekly cisplatin subgroup (all P < 0.01), whereas induction chemotherapy plus concurrent chemoradiotherapy could only improve progression-free survival and locoregional recurrence-free survival in the weekly cisplatin subgroup (HR = 0.78, P = 0.02; and HR = 0.66, P = 0.03, respectively).ConclusionsInduction chemotherapy plus concurrent chemoradiotherapy improved survival outcomes in patients with locally advanced nasopharyngeal carcinoma versus concurrent chemoradiotherapy. For the weekly cisplatin regimen subgroup, it did not improve remote control or overall survival versus concurrent chemoradiotherapy alone, warranting further clarification.

Project description:BackgroundConcurrent chemoradiotherapy followed by adjuvant chemotherapy (CCRT-AC) is currently recommended as the standard treatment for locally advanced nasopharyngeal carcinoma (LA-NPC). Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy (NAC-CCRT) is an alternative strategy for decreasing tumor size and controlling micrometastases before main treatment. The aim of this study was to investigate and compare survival outcomes between LA-NPC patients treated with CCRT-AC and those treated with NAC-CCRT.MethodsThis retrospective cohort study included consecutive histologically confirmed LA-NPC patients that were treated with NAC-CCRT or CCRT-AC at Siriraj Hospital during the March 2010 to October 2014 study period. CCRT in both protocols consisted of 3-week cycles of cisplatin 100 mg/m2 with concurrent radiotherapy. Either NAC or AC consisted of 3-week cycles of cisplatin on day 1 and fluorouracil/leucovorin on days 1-4 for a maximum three cycles. The primary endpoint was 5-year overall survival (OS). Flexible parametric survival analysis was used, because the proportional hazards assumption of Cox regression was violated.ResultsOf the 266 LA-NPC patients that received treatment during the study period, 79 received NAC-CCRT and 187 received CCRT-AC. Median follow-up was 37 months. Significantly more patients with advanced clinical stage (stage IVA-IVB) received NAC-CCRT (86% in NAC-CCRT vs. 29% in CCRT-AC; p?<?0.001). Compared to CCRT-AC in crude analysis, 3-year and 5-year OS of NAC-CCRT were 72% vs. 86% and 62% vs. 75% respectively (p?=?0.059). Interestingly, the 3-year and 5-year post-estimation adjusted OS was 84% and 74% for NAC-CCRT and 81% and 70% for CCRT-AC, respectively (HR: 0.83, 95% confidence interval (CI): 0.45-1.56; p?=?0.571). Also, adjusted analysis of distant-metastasis survival, NAC-CCRT showed HR was 0.79 (95% CI:0.37-1.72, p?=?0.557). Conversely, adjusted analysis of locoregional relapse (LLR)-free survival revealed NAC-CCRT to have a significantly higher risk of LRR (HR: 2.18, 95% CI: 0.98-4.87; p?=?0.057).ConclusionsThe results suggested that prognosis in the NAC-CCRT treated patients was not superior to that of the CCRT-AC treated individuals. In patients that receive neoadjuvant chemotherapy, locoregional relapse should be of concern. High-risk distant metastasis patients (N3 stage) that could achieve survival advantage from NAC-CCRT is an interesting and important topic for further study.

Project description:BackgroundLinc00312 is dysregulated in nasopharyngeal carcinoma (NPC) and participates in the initiation and progression of NPC. Our previous studies suggested that linc00312 was able to enhance the sensitivity of NPC cells to irradiation and NPC patients with higher expression of linc00312 was associated with better short-term curative effect and overall survival. The single nucleotide polymorphisms (SNPs) of lncRNAs may influence the disease course and outcome by affecting the expression, secondary structure or function of lncRNAs. However, the role of SNPs in linc00312 on the occurrence and survival of NPC remains unknown.MethodsWe recruited 684 NPC patients and 823 healthy controls to evaluate the association between linc00312 SNPs and NPC susceptibility by using multivariate logistic regression analysis. Kaplan-Meier analysis and Cox proportional hazards regression were applied to assess the effect of linc00312 SNPs on the survival of NPC patients. The relative expression of linc00312 in NPC tissues was determined by real-time PCR. The interaction between linc00312 and mir-411-3p was explored by luciferase reporter assay. In silico prediction of the changes on linc00312 folding structure was conducted by RNAfold WebServer.ResultWe demonstrated that rs12497104 (G > A) GA genotype carriers had a higher risk than others for suffering from NPC (GA vs GG, OR = 1.437, P = 0.003). Besides, patients with rs12497104 AA genotype showed a poorer overall survival in contrast to GG genotype (AA vs GG, HR = 2.117, P = 0.011). In addition, the heterozygous carriers of rs15734 (G > A) and rs164966 (A > G) were correlated with decreased risk of NPC (GA vs GG, OR = 0.778, P = 0.031; GA vs AA, OR = 0.781, P = 0.033, respectively). We found that the three SNPs might influence the expression of linc00312 in a genotype specific feature. The local centroid secondary structure as well as the minimum free energy of linc00312 were changed following the candidate SNPs alterations. Besides, we revealed that the G to A alteration at rs12497104 disrupted the binding between mir-411-3p and linc00312.ConclusionOur results indicated genetic polymorphisms of linc00312 might serve as potential biomarkers for NPC carcinogenesis and prognosis.

Dataset Information

Genetic polymorphisms of long non-coding RNA GAS5 predict platinum-based concurrent chemoradiotherapy response in nasopharyngeal carcinoma patients.

Publications

Genetic polymorphisms of long non-coding RNA GAS5 predict platinum-based concurrent chemoradiotherapy response in nasopharyngeal carcinoma patients.

Similar Datasets

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