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1.
Ling Zhang Guanghui Gao Xuefei Li Shengxiang Ren Aiwu Li Jianfang Xu Jie Zhang Caicun Zhou 《PloS one》2012,7(10)
New therapeutic approaches are being developed based on the findings that several genetic abnormalities underlying non-small-cell lung cancer (NSCLC) could influence chemosensitivity. In this study, we assessed whether polymorphisms in genes of nucleotide excision repair (NER) pathway, including ERCC5, ERCC6, MMS19L, CCNH, XPC, RRM1, can affect the tolerability of platinum-based chemotherapy in NSCLC patients. We used AllGloTM probe to assess genotyping and polymorphisms in 388 stage IIIB and IV NSCLC patients treated with platinum-based chemotherapy. MMS19L might be associated with the adverse events of chemotherapy in NSCLC, especially for all grade leucopenia (P = 0.020), all grade jaundice (P = 0.037) and all grade creatinine increasing (P = 0.013). In terms of grade 3/4 adverse events, MMS19L was related with total grade 3/4 adverse events (P = 0.024) and grade 3/4 thrombocytopenia (P = 0.035), while RRM1 was related with total grade 3/4 adverse events (P = 0.047) and grade 3/4 vomiting (P = 0.046). ERCC5 was related with more infection (P = 0.017). We found that some SNPs in NER pathway genes were correlated with toxicity treated with double chemotherapy in advanced NSCLC patients, especially for SNPs of MMS19L, RRM1 and ERCC5. 相似文献
2.
Hekun Jin Xiaoxue Xie Hui Wang Jun Hu Feng Liu Zhigang Liu Jumei Zhou Yingying Zhang Xuping Xi Bingqiang Hu Yuping Liao Jingtian Tang 《PloS one》2014,9(7)
Background
Single nucleotide polymorphisms (SNPs) in DNA repair genes can alter gene expression and activity and affect response to cancer treatment and, correspondingly, survival. The present study was designed to evaluate the utility of the XRCC1 Arg399Gln and ERCC1 Cys8092Ala SNPs, measured in pretreatment biopsy samples, as predictors of response to radiotherapy in patients with non-metastatic nasopharyngeal carcinoma (NPC).Materials and methods
The study included 75 consecutive patients with stage II-IVA-B NPC. XRCC1 Arg399Glu and ERCC1 Cys8092Ala SNPs were identified from paraffin-embedded biopsy specimens via Sanger sequencing. Expression of p53 and pAkt protein was analyzed by immunohistochemical staining. Potential relationships between genetic polymorphisms and progression-free survival (PFS) were analyzed by using a Cox proportional hazards model, the Kaplan-Meier method, and the log-rank test.Results
Multivariate analysis showed that carriers of the ERCC1 8092 Ala/Ala genotype [hazard ratio (HR) 1.882; 95% confidence interval (CI) 1.031–3.438; P = 0.039] and heavy smokers (≥20 pack-years) carrying the XRCC1 Arg/Arg genotype (HR 2.019; 95% CI 1.010–4.036; P = 0.047) had significantly lower PFS rates. Moreover, combined positive expression of p53 and pAkt led to significantly increased PFS in subgroups carrying the XRCC1 Gln allele (HR 7.057; 95% CI 2.073–24.021; P = 0.002) or the ERCC1 Cys allele (HR 2.568; 95% CI 1.056–6.248; P = 0.038).Conclusions
The ERCC1 Cys8092Ala polymorphism is an independent predictor of response to radiotherapy for NPC, and the XRCC1 Arg399Glu mutation combined with smoking status seems to predict PFS as well. Our results further suggest a possible correlation between these genetic polymorphisms and p53 protein status on survival. 相似文献3.
Recently, the correlation between the efficacy of platinum-based chemotherapy and ERCC1 expression in patients with SCLC has attracted wide-spread attention, and a lot of investigations have been conducted, whereas conflicting results were presented. Therefore, we performed the present meta-analysis of eligible studies to derive a more precise evaluation of the association between ERCC1 expression and the clinical outcome in SCLC patients receiving platinum-based chemotherapy. A literature search for relevant studies was conducted in the electronic databases of PubMed, EMBASE and Web of Science. The inclusive criteria were SCLC patients treated by platinum-based chemotherapy, and evaluated the relationship between ERCC1 expression and the clinical outcomes [including overall response rate (ORR), overall survival (OS) or progression-free survival (PFS)]. Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) was calculated to assess the risk. A total of nine studies including 1129 patients were included in final analysis. Our analysis indicated that positive/high ERCC1 expression was associated with unfavorable OS (HR = 1.18, 95%CI = 1.02–1.37) and PFS (HR = 1.46, 95%CI = 1.14–1.88). Subgroup analysis according to disease stage suggested the significant relationship was found in limited stage (LS-SCLC), but not in extensive stage (ES-SCLC). However, no significant association was found between ERCC1 expression and ORR. Our analysis suggested ERCC1 expression may be a prognostic factor in SCLC patients receiving platinum-based chemotherapy, especially for LS-SCLC. 相似文献
4.
Objectives
To comprehensively evaluate the association of ERCC1 C8092A and ERCC2 Lys751Gln polymorphisms with the risk of glioma.Methods
Potential studies were searched and selected through the Pubmed/MEDLINE, EMBASE, the China National Knowledge Infrastructure (CNKI) platforms, WanFang and VIP database up to June 2013. Two investigators independently reviewed full text and included studies met inclusion criteria. Combined odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated in a fixed-effects model or a random-effects model according to results of heterogeneity test. All analyses were performed by Revman 5.2 and Stata 10.0 software.Results
A total of 10 studies were included in our meta-analysis, including 3,580 glioma patients and 4,728 controls. Overall, ERCC1 C8092A polymorphism was associated with the risk of glioma (AA vs. CC: OR = 1.29, 95%CI: 1.07–1.55, P = 0.01; recessive model: OR = 1.29; 95% CI: 1.07–1.55, P = 0.01). When stratified by ethnicity, significant association was only observed in the Chinese population (AA vs. CC: OR = 1.37, 95%CI: 1.03–1.81, P = 0.03; recessive model: OR = 1.34; 95% CI: 1.02–1.75, P = 0.04). For ERCC2 Lys751Gln polymorphism, no significant association was found between ERCC2 Lys751Gln polymorphism and the risk of glioma in different genetic models. A significant association of ERCC2 Lys751Gln polymorphism with the risk of glioma was identified in the Caucasian population under recessive model (OR = 0.87; 95% CI: 0.78–0.98, P = 0.02), but not in the Chinese population.Conclusion
This meta-analysis suggested that the AA genotype of ERCC1 C8092A polymorphism might increase the susceptibility of glioma in the Chinese population. And the TT genotype of ERCC2 Lys751Gln polymorphism may decrease the risk of glioma in the Caucasian population. But the small number of studies and moderate methodological quality require cautious interpretation of the study results. 相似文献5.
The published data on the predictive role of ERCC1 polymorphisms in lung cancer risk and survival of patients with advanced non-small cell lung cancer (NSCLC) receiving platinum-based chemotherapy remains inconsistent. The aim of this meta-analysis was to determine the role of ERCC1 gene polymorphisms (C118T and C8092A) in this clinical situation. Eligible studies were included and assessed for quality using multiple search strategies. Thirty-nine published papers involving 9615 cases (4606 with Stage III/IV disease) and 5542 controls were included in the analysis. Pooled odds ratios (OR) or hazard ratios (HR) with 95% confidence intervals (CI) were used to estimate risk. ERCC1-C118T was associated with lung cancer risk. The OR was 0.90 (95% CI: 0.81–0.99, p = 0.043) in an additive genetic model (C allele vs. T allele) and 0.77 (95% CI: 0.63–0.95, p = 0.013) in a recessive genetic model (CC/CT vs. TT). The corresponding risk was 0.74 (95% CI: 0.58–0.94, p = 0.013) based on a homozygous comparison (CC vs. TT). No significant correlation was found for ERCC1 C8092A and there was no obvious relationship between ERCC1 C118T/C8092A polymorphisms and objective response to platinum-based chemotherapy. Overall survival (OS) of patients with non-small cell lung cancer (NSCLC) receiving platinum-based chemotherapy was significantly related to ERCC1 C118T (HR: 1.29, 95% CI: 1.07–1.56, p = 0.007, CT/TT vs. CC). There was no relationship between ERCC1 C8092A and survival (HR: 1.32, 95% CI: 0.84–2.10, p = 0.23, CA/AA vs. CC). These findings suggest that ERCC1 C118T polymorphisms may serve as a biomarker for lung cancer risk and have prognostic value in patients with advanced non-small cell lung cancer (NSCLC) undergoing platinum-based treatment. Further studies with larger numbers of subjects from a worldwide arena are needed to validate the associations. 相似文献
6.
Hui-Hui Cao Chun-Peng Zheng Shao-Hong Wang Jian-Yi Wu Jin-Hui Shen Xiu-E Xu Jun-Hui Fu Zhi-Yong Wu En-Min Li Li-Yan Xu 《PloS one》2014,9(8)
Background
Esophageal squamous cell carcinoma (ESCC) has the highest mortality rates in China. The 5-year survival rate of ESCC remains dismal despite improvements in treatments such as surgical resection and adjuvant chemoradiation, and current clinical staging approaches are limited in their ability to effectively stratify patients for treatment options. The aim of the present study, therefore, was to develop an immunohistochemistry-based prognostic model to improve clinical risk assessment for patients with ESCC.Methods
We developed a molecular prognostic model based on the combined expression of axis of epidermal growth factor receptor (EGFR), phosphorylated Specificity protein 1 (p-Sp1), and Fascin proteins. The presence of this prognostic model and associated clinical outcomes were analyzed for 130 formalin-fixed, paraffin-embedded esophageal curative resection specimens (generation dataset) and validated using an independent cohort of 185 specimens (validation dataset).Results
The expression of these three genes at the protein level was used to build a molecular prognostic model that was highly predictive of ESCC survival in both generation and validation datasets (P = 0.001). Regression analysis showed that this molecular prognostic model was strongly and independently predictive of overall survival (hazard ratio = 2.358 [95% CI, 1.391–3.996], P = 0.001 in generation dataset; hazard ratio = 1.990 [95% CI, 1.256–3.154], P = 0.003 in validation dataset). Furthermore, the predictive ability of these 3 biomarkers in combination was more robust than that of each individual biomarker.Conclusions
This technically simple immunohistochemistry-based molecular model accurately predicts ESCC patient survival and thus could serve as a complement to current clinical risk stratification approaches. 相似文献7.
Jun Yin Liming Wang Liang Zheng Xu Wang Yijun Shi Aizhong Shao Guowen Ding Chao Liu Suocheng Chen Weifeng Tang Haiyong Gu 《PloS one》2014,9(7)
Background
Esophageal cancer was the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death in China in 2009. Esophageal squamous cell carcinoma (ESCC) accounts for more than 90 percent of esophageal cancers. Genetic factors probably play an important role in the ESCC carcinogenesis.Methods
We conducted a hospital based case-control study to evaluate functional hTERT rs2736098 G>A and TERT-CLPTM1L rs401681 C>T single nucleotide polymorphisms (SNPs) on the risk of ESCC. Six hundred and twenty-nine ESCC cases and 686 controls were recruited. Their genotypes were determined using the ligation detection reaction (LDR) method.Results
When the TERT-CLPTM1L rs401681 CC homozygote genotype was used as the reference group, the CT genotype was associated with a significantly decreased risk of ESCC (adjusted OR = 0.74, 95% CI = 0.58–0.94, p = 0.012); the CT/TT variants were associated with a 26% decreased risk of ESCC (adjusted OR = 0.74, 95% CI = 0.59–0.93, P = 0.009). The significantly decreased risk of ESCC associated with the TERT-CLPTM1L rs401681 C>T polymorphism was associated with male sex, young age (<63 years in our study) and alcohol consumption. No association between the hTERT rs2736098 G>A polymorphism and ESCC risk was observed.Conclusion
TERT-CLPTM1L rs401681 CT and CT/TT genotypes were associated with decreased risk of ESCC, particularly among men, young patients and those reported to be drinkers. However, our results are preliminary conclusions. Larger studies with more rigorous study designs are required to confirm the current findings. 相似文献8.
Qin Qin Chi Zhang Xi Yang Hongcheng Zhu Baixia Yang Jing Cai Hongyan Cheng Jianxin Ma Jing Lu Liangliang Zhan Jia Liu Zheming Liu Liping Xu Xinchen Sun 《PloS one》2013,8(11)
Objective
Xeroderma pigmentosum group D (XPD) is an essential gene involved in the nucleotide excision repair (NER) pathway. Two commonly studied single nucleotide polymorphisms (SNPs) of XPD (Lys751Gln, A>C, rs13181; Asp312Asn, G>A, rs1799793) are implicated in the modulation of DNA repair capacity, thus related to the responses to platinum-based chemotherapy. Here we performed a meta-analysis to better evaluate the association between the two XPD SNPs and clinical outcome of platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients.Methods
A comprehensive search of PubMed database was conducted to identify relevant articles. Primary outcomes included objective response (i.e., complete response + partial response vs. stable disease + progressive disease), progression-free survival (PFS) and overall survival (OS). The pooled and 95% confidence intervals (CIs) of ORs (odds ratios) and HRs (hazard ratios) were estimated using the fixed or random effect model.Results
Twenty-four studies were eligible according to the inclusion criteria. None of the XPD Lys751Gln/Asp312Asn polymorphisms was associated with objective response, PFS or OS in NSCLC patients treated with platinum drugs. However, in stratified analysis by ethnicity, the XPD Lys751Gln (A>C) polymorphism was not significantly associated with increased response in Caucasians (OR = 1.35, 95%CI = 1.0–1.83, P = 0.122 for heterogeneity) but was associated with decreased PFS in Asians (HR = 1.39, 95%CI = 1.07–1.81, P = 0.879 for heterogeneity). Furthermore, a statistically significant difference existed in the estimates of effect between the two ethnicities (P = 0.014 for TR; P<0.001 for PFS).Conclusions
XPD Lys751Gln (A>C) may have inverse predictive and prognostic role in platinum-based treatment of NSCLC according to different ethnicities. Further studies are needed to validate our findings. 相似文献9.
It is hypothesized that high expression of the excision repair cross-complementation group 1 (ERCC1) gene might be a positive
prognostic factor, but predict decreased sensitivity to platinum-based chemotherapy. Results from the published data are inconsistent.
To derive a more precise estimation of the relationship between ERCC1 and the prognosis and predictive response to chemotherapy
of non-small cell lung cancer (NSCLC), a meta-analysis was performed. An electronic search of the PubMed and Embase database
was performed. Hazard ratio (HR) for overall survival (OS) was pooled in early stage patients received surgery alone to analyze
the prognosis of ERCC1 on NSCLC. HRs for OS in patients received surgery plus adjuvant chemotherapy and in patients received
palliative chemotherapy and relative risk (RR) for overall response to chemotherapy were aggregated to analyze the prediction
of ERCC1 on NSCLC. The pooled HR indicated that high ERCC1 levels were associated with longer survival in early stage patients
received surgery alone (HR, 0.69; 95% confidence interval (CI), 0.58–0.83; P = 0.000). There was no difference in survival between high and low ERCC1 levels in patients received surgery plus adjuvant
chemotherapy (HR, 1.41; 95% CI, 0.93–2.12; P = 0.106). However, high ERCC1 levels were associated with shorter survival and lower response to chemotherapy in advanced
NSCLC patients received palliative chemotherapy (HR, 1.75; 95% CI, 1.39–2.22; P = 0.000; RR, 0.77; 95% CI, 0.64–0.93; P = 0.007; respectively). The meta-analysis indicated that high ERCC1 expression might be a favourable prognostic and a drug
resistance predictive factor for NSCLC. 相似文献
10.
Thomas John Maud H. W. Starmans Yao-Tseng Chen Prudence A. Russell Stephen A. Barnett Shane C. White Paul L. Mitchell Marzena Walkiewicz Arun Azad Philippe Lambin Ming-Sound Tsao Siddhartha Deb Nasser Altorki Gavin Wright Simon Knight Paul C. Boutros Jonathan S. Cebon 《PloS one》2013,8(7)
Background
Cancer-Testis Antigens (CTAs) are immunogenic proteins that are poor prognostic markers in non-small cell lung cancer (NSCLC). We investigated expression of CTAs in NSCLC and their association with response to chemotherapy, genetic mutations and survival.Methods
We studied 199 patients with pathological N2 NSCLC treated with neoadjuvant chemotherapy (NAC; n = 94), post-operative observation (n = 49), adjuvant chemotherapy (n = 47) or unknown (n = 9). Immunohistochemistry for NY-ESO-1, MAGE-A and MAGE-C1 was performed. Clinicopathological features, response to neoadjuvant treatment and overall survival were correlated. DNA mutations were characterized using the Sequenom Oncocarta panel v1.0. Affymetrix data from the JBR.10 adjuvant chemotherapy study were obtained from a public repository, normalised and mapped for CTAs.Results
NY-ESO-1 was expressed in 50/199 (25%) samples. Expression of NY-ESO-1 in the NAC cohort was associated with significantly increased response rates (P = 0.03), but not overall survival. In the post-operative cohort, multivariate analyses identified NY-ESO-1 as an independent poor prognostic marker for those not treated with chemotherapy (HR 2.61, 95% CI 1.28–5.33; P = 0.008), whereas treatment with chemotherapy and expression of NY-ESO-1 was an independent predictor of improved survival (HR 0.267, 95% CI 0.07–0.980; P = 0.046). Similar findings for MAGE-A were seen, but did not meet statistical significance. Independent gene expression data from the JBR.10 dataset support these findings but were underpowered to demonstrate significant differences. There was no association between oncogenic mutations and CTA expression.Conclusions
NY-ESO-1 was predictive of increased response to neoadjuvant chemotherapy and benefit from adjuvant chemotherapy. Further studies investigating the relationship between these findings and immune mechanisms are warranted. 相似文献11.
Li Shang Hui-Juan Liu Jia-Jie Hao Yan-Yi Jiang Feng Shi Yu Zhang Yan Cai Xin Xu Xue-Mei Jia Qi-Min Zhan Ming-Rong Wang 《PloS one》2014,9(10)
Esophageal squamous cell carcinoma (ESCC) is a common cancer with poor prognosis. In order to identify useful biomarkers for accurately classifying prognostic risks for ESCC patients, we examined the expression of six proteins by immunohistochemistry (IHC) in 590 paraffin-embedded ESCC samples. The candidate proteins include p53, EGFR, c-KIT, TIMP1 and PI3K-p110α reported to be altered in ESCC tissues as well as another important component of PI3K, PI3K-p85α. Of the six proteins tested, p53, EGFR, c-KIT, TIMP1 and PI3K-p85α were detected with high expression in 43.0%, 36.6%, 55.9%, 70.7% and 57.1% of tumors, respectively. Significant associations were found between high expression of PI3K-p85α, EGFR and p53 and poor prognosis (P = 0.00111; 0.00001; 0.00426). Applying these three proteins as an IHC panel could divide patients into different subgroups (P<0.000001). Multivariate cox regression analysis indicated that the three-protein panel was an independent prognostic factor with very high statistical significance (HR = 2.090, 95% CI: 1.621–2.696, P = 0.00000001). The data suggest that the three-protein panel of PI3K-p85α, EGFR and p53 is an important candidate biomarker for the prognosis of patients with ESCC. 相似文献
12.
Chunguang Li Zhigang Li Maoling Zhu Tiejun Zhao Ling Chen Weidan Ji Hezhong Chen Changqing Su 《PloS one》2012,7(9)
Background
The prognostic significance of survivin for survival of patients with esophageal squamous cell carcinoma (ESCC) remains controversial. Thus, meta-analysis of the literatures was performed in order to demonstrate its expression impact on ESCC clinicopathological features and prognosis.Methodology
Relevant literatures were searched using PubMed, EMBASE and Medline Databases. Revman5.0 software was used to pool eligible studies and summary hazard ratio (HR). Correlation between survivin expression and clinicopathological features of ESCC was analyzed.Principal Findings
Final analysis of 523 patients from 7 eligible studies was performed. Combined HR of survivin location in nuclei suggested that survivin expression has an unfavorable impact on ESCC patients'' survival (n = 277 in 3 studies; HR = 1.89, 95% CI: 1.45–2.96; Z = 4.69; P<0.0001). Nevertheless, combined HR of survivin location in cytoplasm displayed that survivin expression has no significance for prognosis of ESCC patients (n = 113 in 2 studies; HR = 0.96, 95% CI: 0.96–5.69; Z = 0.04; P = 0.97); Combined odds ratio (OR) of survivin location in cytoplasm indicated that survivin expression is associated with ESCC advanced stage (n = 113 in 2 studies; OR = 0.36, 95% CI: 0.14–0.93; Z = 2.10; P = 0.04). Whereas, combined OR of survivin location in nuclei exhibited that survivin over-expression has no correlation with cell differentiation grade, lymph node status, depth of invasion, stage, and metastasis of ESCC.Conclusions
This study showed that survivin expression detected by immunohistochemistry seems to be associated with a worse prognosis of ESCC patients. Survivin subcellular location may be an important factor impacting on ESCC development. Larger prospective studies should be performed to evaluate the status of survivin in predicting prognosis of patients with ESCC. 相似文献13.
Introduction
X-ray repair cross-complementing protein 3 (XRCC3) is an essential gene involved in the double-strand break repair pathway. Published evidence has shown controversial results about the relationship between XRCC3 Thr241Met polymorphism and clinical outcomes of non-small cell lung cancer (NSCLC) patients receiving platinum-based chemotherapy.Methods
A systematic review and meta-analysis was performed to evaluate the predictive value of XRCC3 Thr241Met polymorphism on clinical outcomes of advanced NSCLC receiving platinum-based chemotherapy. Response to chemotherapy, overall survival (OS) and progression-free survival (PFS) were analyzed.Results
A number of 11 eligible studies were identified according to the inclusion criteria. Carriers of the variant XRCC3 241Met allele were significantly associated with good response to platinum-based chemotherapy (ThrMet/MetMet vs. ThrThr: OR = 1.509, 95% CI: 1.099–2.072, Pheterogeneity = 0.618). The XRCC3 Thr241Met polymorphism was not associated with OS (MetMet vs. ThrThr, HR = 0.939, 95% CI:0.651–1.356, Pheterogeneity = 0.112) or PFS (MetMet vs. ThrThr, HR = 0.960, 95% CI: 0.539–1.710, Pheterogeneity = 0.198). Additionally, no evidence of publication bias was observed.Conclusions
This systematic review and meta-analysis shows that carriers of the XRCC3 241Met allele are associated with good response to platinum-based chemotherapy in advanced NSCLC, while the XRCC3 Thr241Met polymorphism is not associated with OS or PFS. 相似文献14.
Jing He Yu Xu Li-Xin Qiu Jin Li Xiao-Yan Zhou Meng-Hong Sun Jiu-Cun Wang Ya-Jun Yang Li Jin Qing-Yi Wei Yanong Wang 《PloS one》2012,7(11)
Background
Inherited functional single nucleotide polymorphisms (SNPs) in DNA repair genes may alter DNA repair capacity and thus contribute to cancer risk.Methods
Three ERCC1 functional SNPs (rs2298881C>A, rs3212986C>A and rs11615G>A) and two XPF/ERCC4 functional SNPs (rs2276466C>G and rs6498486A>C) were genotyped for 1125 gastric adenocarcinoma cases and 1196 cancer-free controls by Taqman assays. Odds ratios (OR) and 95% confidence intervals (CI) were used to estimate risk associations, and false-positive report probabilities (FPRP) were calculated for assessing significant findings.Results
ERCC1 rs2298881C and rs11615A variant genotypes were associated with increased gastric cancer risk (adjusted OR = 1.33, 95% CI = 1.05–1.67 for rs2298881 AC/CC and adjusted OR = 1.23, 95% CI = 1.05–1.46 for rs11615 AG/AA, compared with their common genotype AA and GG, respectively). Patients with 2–3 ERCC1 risk genotypes had significant increased risk (adjusted OR = 1.56, 95% CI = 1.27–1.93), compared with those with 0–1 ERCC1 risk genotypes, and this risk was more significantly in subgroups of never drinkers, non-gastric cardia adenocarcinoma (NGCA) and clinical stage I+II. All these risks were not observed for XPF SNPs.Conclusions
These findings suggest that functional ERCC1 SNPs may contribute to risk of gastric cancer. Larger and well-designed studies with different ethnic populations are needed to validate our findings. 相似文献15.
Shun Lu Barbara Pardini Bowang Cheng Alessio Naccarati Stefanie Huhn Veronika Vymetalkova Ludmila Vodickova Thomas Buchler Kari Hemminki Pavel Vodicka Asta F?rsti 《PloS one》2014,9(10)
Interferon (IFN) signaling has been suggested to play an important role in colorectal carcinogenesis. Our study aimed to examine potentially functional genetic variants in interferon regulatory factor 3 (IRF3), IRF5, IRF7, type I and type II IFN and their receptor genes with respect to colorectal cancer (CRC) risk and clinical outcome. Altogether 74 single nucleotide polymorphisms (SNPs) were covered by the 34 SNPs genotyped in a hospital-based case-control study of 1327 CRC cases and 758 healthy controls from the Czech Republic. We also analyzed these SNPs in relation to overall survival and event-free survival in a subgroup of 483 patients. Seven SNPs in IFNA1, IFNA13, IFNA21, IFNK, IFNAR1 and IFNGR1 were associated with CRC risk. After multiple testing correction, the associations with the SNPs rs2856968 (IFNAR1) and rs2234711 (IFNGR1) remained formally significant (P = 0.0015 and P<0.0001, respectively). Multivariable survival analyses showed that the SNP rs6475526 (IFNA7/IFNA14) was associated with overall survival of the patients (P = 0.041 and event-free survival among patients without distant metastasis at the time of diagnosis, P = 0.034). The hazard ratios (HRs) for rs6475526 remained statistically significant even after adjustment for age, gender, grade and stage (P = 0.029 and P = 0.036, respectively), suggesting that rs6475526 is an independent prognostic marker for CRC. Our data suggest that genetic variation in the IFN signaling pathway genes may play a role in the etiology and survival of CRC and further studies are warranted. 相似文献
16.
ML Zhu TY Shi HC Hu J He M Wang L Jin YJ Yang JC Wang MH Sun H Chen KL Zhao Z Zhang HQ Chen JQ Xiang QY Wei 《PloS one》2012,7(7):e41500
Background
Excision repair cross complementing group 5 (ERCC5 or XPG) plays an important role in regulating DNA excision repair; its functional single nucleotide polymorphisms (SNPs) may alter DNA repair capacity and thus contribute to cancer risk.Methodology/Principal Findings
In a hospital-based case-control study of 1115 esophageal squamous cell carcinoma (ESCC) cases and 1117 cancer-free controls, we genotyped three potentially functional SNPs of ERCC5 (SNPs, rs2296147T>C, rs2094258C>T and rs873601G>A) and estimated crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for their associations with risk of ESCC using unconditional logistic regression models. We also calculated false-positive report probabilities (FPRPs) for significant findings. We found that compared with the TT genotype, ERCC5 rs2296147 C variant genotypes were associated with a significantly lower ESCC risk (CT: adjusted OR = 0.76, 95% CI = 0.63–0.93, CT/CC: adjusted OR = 0.80, 95% CI = 0.67–0.96); however, this risk was not observed for the other two SNPs (rs2094258C>T and rs873601 G>A), nor in further stratification and haplotype analysis.Conclusions/Significances
These findings suggested that ERCC5 polymorphisms may contribute to risk of ESCC in Eastern Chinese populations, but the effect was weak and needs further validation by larger population-based case-control studies. 相似文献17.
Sveinung W. Sorbye Thomas K. Kilvaer Andrej Valkov Tom Donnem Eivind Smeland Khalid Al-Shibli Roy M. Bremnes Lill-Tove Busund 《PloS one》2012,7(10)
Purpose
The purpose of this study is to clarify the prognostic significance of expression of Jab1, p16, p21, p62, Ki67 and Skp2 in soft tissue sarcomas (STS). Optimised treatment of STS requires better identification of high risk patients who will benefit from adjuvant therapy. The prognostic significance of Jab1, p16, p21, p62, Ki67 and Skp2 in STS has not been sufficiently investigated.Experimental Design
Tissue microarrays from 193 STS patients were constructed from duplicate cores of viable and representative neoplastic tumor areas. Immunohistochemistry was used to evaluate the expression of Jab1, p16, p21, p62, Ki67 and Skp2.Results
In univariate analyses, high tumor expression of Ki67 (P = 0.007) and Skp2 (P = 0.050) correlated with shorter disease-specific survival (DSS). In subgroup analysis, a correlation between Skp2 and DSS was seen in patients with malignancy grade 1 or 2 (P = 0.027), tumor size >5 cm (P = 0.018), no radiotherapy given (P = 0.029) and no chemotherapy given (P = 0.017). No such relationship was apparent for Jab1, p16, p21 and p62; but p62 showed a positive correlation to malignancy grade (P = 0.019). Ki67 was strongly positively correlated to malignancy grade (P = 0.001). In multivariate analyses, Skp2 was an independent negative prognostic factor for DSS in women (P = 0.009) and in patients without administered chemotherapy or radiotherapy (P = 0.026).Conclusions
Increased expression of Skp2 in patients with soft tissue sarcomas is an independent negative prognostic factor for disease-specific survival in women and in patients not administered chemotherapy or radiotherapy. Besides, further studies are warranted to explore if adjuvant chemotherapy or radiotherapy improve the poor prognosis of STS with high Skp2 expression. 相似文献18.
Guofeng Yue Jia Wei Xiaoping Qian Lixia Yu Zhengyun Zou Wenxian Guan Hao Wang Jie Shen Baorui Liu 《PloS one》2013,8(6)
Objective
The present study was designed to examine the anticancer effect of Traditional Chinese Medicine of polyphyllin I (PPI) and evodiamine (EVO) on freshly–removed gastric tumor tissues.Methods
Sixty freshly–removed gastric tumor tissues were collected. Their sensitivity to PPI, EVO, platinum (Pt), 5-FU, irinotecan (CPT-11) were determined by histoculture drug response assay (HDRA). Those samples were also formalin-fixed and paraffin-embedded, which were used to examine the mRNA expression levels of aprataxin(APTX), excision repair cross-complementing 1(ERCC1), thymidylate synthase(TS) and topoisomerase I(TOPO1) by quantitative RT-PCR. The association of the gene expression levels and in vitro sensitivity were analyzed.Results
PPI, EVO, Pt, 5-FU and CPT-11 had anticancer effects on the freshly-removed gastric tumor tissues with average inhibition rates of 20.64%±14.25% for PPI, 21.14%±13.43% for EVO, 50.57%±22.37% for Pt, 53.54%±22.03% for 5-FU, and 39.33%±24.79% for CPT-11, respectively. Combination of PPI and Pt, EVO and Pt, EVO and 5-FU had higher inhibition rates than any single drug of them (P<0.001, P = 0.028, P = 0.017, respectively). The mRNA expression levels of ERCC1 were correlated with Pt sensitivity (rho = −0.645, P<0.001); the mRNA expression levels of TS were correlated with 5-FU sensitivity (rho = −0.803, P<0.001). There were also weak but significant correlations between APTX mRNA expression levels and CPT-11 sensitivity (rho = −0.376, P = 0.017) or EVO sensitivity (rho = −0.322, P = 0.036). ERCC1 mRNA expression levels was markedly suppressed by the presentation of PPI (P = 0.001) and slightly suppressed by the presentation of EVO (P = 0.04); whereas, TS mRNA expression levels was markedly decreased by the presentation of EVO (P = 0.017) and slightly decreased by the presentation of PPI (P = 0.047).Conclusion
PPI and EVO both could inhibit the activity of freshly-removed gastric tumor, and they could enhance the anticancer effect of Pt and 5-FU by reducing the mRNA expression levels of ERCC1 and TS. 相似文献19.
Tanguy Y. Seiwert XiaoZhe Wang Jana Heitmann Vivian Villegas-Bergazzi Kam Sprott Stephen Finn Esther O'Regan Allan D. Farrow Ralph R. Weichselbaum Mark W. Lingen Ezra E. W. Cohen Kerstin Stenson David T. Weaver Everett E. Vokes 《PloS one》2014,9(7)
Background
Induction chemotherapy is a common therapeutic option for patients with locoregionally-advanced head and neck cancer (HNC), but it remains unclear which patients will benefit. In this study, we searched for biomarkers predicting the response of patients with locoregionally-advanced HNC to induction chemotherapy by evaluating the expression pattern of DNA repair proteins.Methods
Expression of a panel of DNA-repair proteins in formalin-fixed paraffin embedded specimens from a cohort of 37 HNC patients undergoing platinum-based induction chemotherapy prior to definitive chemoradiation were analyzed using quantitative immunohistochemistry.Results
We found that XPF (an ERCC1 binding partner) and phospho-MAPKAP Kinase 2 (pMK2) are novel biomarkers for HNSCC patients undergoing platinum-based induction chemotherapy. Low XPF expression in HNSCC patients is associated with better response to induction chemoradiotherapy, while high XPF expression correlates with a worse response (p = 0.02). Furthermore, low pMK2 expression was found to correlate significantly with overall survival after induction plus chemoradiation therapy (p = 0.01), suggesting that pMK2 may relate to chemoradiation therapy.Conclusions
We identified XPF and pMK2 as novel DNA-repair biomarkers for locoregionally-advanced HNC patients undergoing platinum-based induction chemotherapy prior to definitive chemoradiation. Our study provides insights for the use of DNA repair biomarkers in personalized diagnostics strategies. Further validation in a larger cohort is indicated. 相似文献20.
Xianglin Yuan Qingyi Wei Ritsuko Komaki Zhensheng Liu Ju Yang Susan L. Tucker Ting Xu John V. Heymach Charles Lu James D. Cox Zhongxing Liao 《PloS one》2013,8(6)