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Nanjing, China

Tang S.,Nanjing Medical University | Pan Y.,Nanjing Medical University | Wang Y.,Nanjing Thoracic Hospital | Hu L.,Nanjing Medical University | And 10 more authors.
Annals of Surgical Oncology

Background Lung cancer, especially non-small cell lung cancer (NSCLC), is the leading cause of cancer-related deaths all over the world. Studies have indicated that molecular biomarkers, including genetic variants, may provide additional values for the targeted treatments and clinical outcomes of NSCLC patients. To better understand the effects of molecular biomarkers on the treatment of NSCLC, we conducted a genome-wide analysis to investigate the prognostic implications of genetic variants in early-stage NSCLC patients with surgery. Methods A genome wide scan of 906,703 single-nucleotide polymorphisms (SNPs) was conducted in a cohort with 365 early-stage NSCLC patients with surgery, followed by a fast-track replication in another independent cohort of 327 NSCLC patients from Nanjing, China. Cox models were used to screen and validate significant SNPs associated with the overall survival of early-stage NSCLC patients. Results We found that rs10023113 in calcium/calmodulin-dependent protein kinase II delta (CAMK2D) was consistently associated with survival of early-stage NSCLC in the GWAS scan and the replication cohort [GWAS scan: hazard ratio (HR) 2.84; 95 % confidence interval (CI) 1.90-4.23, P = 1.29 × 10-6; replication cohort: HR 2.19, 95 % CI 1.15-4.21, P = 1.80 × 10-2]. When combining all the patients, the results showed that the variant allele of rs10023113 was significantly associated with poor prognosis of early-stage NSCLC with P value of 3.40 × 10-7 (HR 2.30, 95 % CI 1.67-3.17). Conclusions These findings suggest that CAMK2D rs10023113 may be a potentially prognostic marker for overall survival of early-stage NSCLC patients in Chinese population. © 2014 Society of Surgical Oncology. Source

Hong M.,Nanjing Thoracic Hospital | Jiang Z.,Nanjing Southeast University | Zhou Y.-F.,Nanjing Jiangbei Peoples Hospital
Asian Pacific Journal of Cancer Prevention

Background: To investigate the effects of double radiofrequency hyperthermia on Th1/Th2 cells in esophageal cancer patients treated with radiotherapy. Materials and Methods: 22 patients with esophageal cancer were divided into a radiotherapy group (10 cases) and a combined group (double radiofrequency hyperthermia combined with radiotherapy group, 12 cases). Both groups received conventional radiotherapy using a cobalt-60 therapy apparatus (TD60-66Gy/30-33F). Patients in the combined group also underwent double radiofrequency hyperthermia (2F/W, 8-10F). Before and after treatment, Th1, Th2, Tc1 and Tc2 cells in peripheral blood were determined with flow cytometry. Results: In the radiotherapy group, Th1 cell contents before and after radiotherapy were 17.5±5.26% and 9.69±4.86%, respectively, with a significant difference (p<0.01). The Th1/Th2 ratio was significantly decreased from 28.2±14.3 to 16.5±10.4 (p<0.01). In the combined group, Th1 cell content before radiotherapy was 15.9±8.18%, and it increased to 18.6±8.84 after radiotherapy (p>0.05), the Th1/Th2 ratio decreasing from 38.4±36.3 to 28.1±24.0 (p>0.05). Changes in Th2, Tc1 and Tc2 cell levels were not significant in the two groups before and after therapy (p>0.05). Conclusions: Double radiofrequency hyperthermia can promote the conversion from Th2 to Th1 cells, and regulate the balance of Th1/Th2 cells. Source

Hu Z.,Nanjing Medical University | Shu Y.,Nanjing Medical University | Chen Y.,Nanjing Medical University | Chen J.,Nanjing Medical University | And 10 more authors.
American Journal of Respiratory and Critical Care Medicine

Rationale: Previously, we reported that common variants in precursor microRNA (pre-miRNA) sequences played a role in the prediction of non-small cell lung cancer (NSCLC) survival. Objectives: To assess whether variants in the pre-miRNA flanking region can influence the clinical behavior of NSCLC. Methods: We conducted a two-stage study to examine the impact of a panel of 85 single-nucleotide polymorphisms on the overall survival of 923 patients with NSCLC (568 in the screening set and 355 in the validation set) in China. Measurements and Main Results: Eleven single-nucleotide polymorphisms were primarily associated with NSCLC survival in the univariate analysis. However, in the validation set, only miR-30c-1 rs928508 was consistently an NSCLC survival predictor and the protective role of rs928508 AG/GG genotypes was more pronounced among early-stage (stage I/II) patients and patients treated with surgery. The area under the curve at Year 5 was significantly increased from 0.658 to 0.741 after adding the miR-30c-1 rs928508 risk score to the traditional clinical risk score (stage and surgery). Furthermore, in the genotype-phenotype correlation analysis, rs928508 AG/GG genotypes were associated with a significantly decreased expression of precursor and mature miR-30c (P = 0.009 and 0.011), but not with that of its primary miRNA. The expression of the host nuclear transcription factor Y gene was correlated with pri-mir-30c-1, but not with rs928508 genotypes, implicating the coregulation of the transcription of nuclear transcription factor Y and pri-mir-30c-1. Conclusions: Our data indicated, for the first time, that genetic polymorphisms in the pre-miRNA flanking region may be prognostic biomarkers of NSCLC, and rs928508 is such a potential candidate. Source

Dong J.,Nanjing Medical University | Dai J.,Nanjing Medical University | Shu Y.,Nanjing Medical University | Pan S.,Nanjing Medical University | And 8 more authors.

Over the last decades, combined chemotherapies that inhibit different signalling pathways together have been demonstrated to be more effective to treat the non-small-cell lung cancer (NSCLC). The epidermal growth factor receptor (EGFR) and the vascular endothelium growth factor (VEGF) are two key targets. Polymorphisms in EGFR and VEGF genes have been identified to be associated with therapy-response and cancer survival. In this study, we hypothesized that single-nucleotide polymorphisms (SNPs) of EGFR and VEGF genes are associated with NSCLC patients' survival in Chinese. Therefore, we screened and genotyped 54 potentially functional SNPs as well as tagging SNPs in these two genes using Illumina Golden Gate platform in 568 NSCLC patients. We found that subjects carrying EGFR rs3735061AA and rs6958497AG/GG genotypes survived significantly shorter time [median survival time (MST): 22.2 and 19.4 months, respectively] than those carrying rs3735061AG/GG (MST: 25.1 months) and rs6958497AA (MST: 25.9 months) (log-rank P = 0.015 for rs3735061 and log-rank P = 0.028 for rs6958497). However, subjects carrying EGFR rs759165AG/AA genotypes survived significantly longer (MST: 38.7 months) than those carrying rs759165GG genotype (MST: 24.7 months) (log-rank P = 0.024). Multivariate Cox regression analyses showed that the genotypes of rs3735061AA and rs6958497AG/GG were associated with a significantly increased risk of death for NSCLC [hazard ratio (HR) = 2.82, 95% confidence interval (CI) = 1.66-4.78 for rs3735061AA and HR = 1.69, 95% CI = 1.26-2.28 for rs6958497AG/GG], whereas the rs759165AG/AA were associated with a 44% significantly decreased risk of death of NSCLC (HR = 0.56, 95% CI = 0.39-0.83). Stepwise COX regression analyses suggested that EGFR rs373506, rs759165 and rs6958497 may be independent candidate biomarkers to predict NSCLC survival in this population. © The Author 2010. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org. Source

Hu L.,Nanjing Medical University | Wu C.,Chinese Academy of Sciences | Zhao X.,Fudan University | Heist R.,Massachusetts General Hospital | And 25 more authors.
Clinical Cancer Research

Purpose: Genetic variation may influence chemotherapy response and overall survival in cancer patients. Experimental design: We conducted a genome-wide scan in 535 advanced-stage non-small cell lung cancer (NSCLC) patients from two independent cohorts (307 from Nanjing and 228 from Beijing). A replication was carried out on an independent cohort of 340 patients from Southeastern China followed by a second validation on 409 patients from the Massachusetts General Hospital (Boston, MA). Results: Consistent associations with NSCLC survival were identified for five single-nucleotide polymorphisms (SNP) in Chinese populations with P values ranging from 3.63 × 10-5 to 4.19 × 10-7 in the additive genetic model. The minor allele of three SNPs (rs7629386 at 3p22.1, rs969088 at 5p14.1, and rs3850370 at 14q24.3) were associated with worse NSCLC survival while 2 (rs41997 at 7q31.31 and rs12000445 at 9p21.3) were associated with better NSCLC survival. In addition, rs7629386 at 3p22.1 (CTNNB1) and rs3850370 at 14q24.3 (SNW1-ALKBH1-NRXN3) were further replicated in the Caucasian population. Conclusion: In this three-stage genome-wide association studies, we identified five SNPs as markers for survival of advanced-stage NSCLC patients treated with first-line platinum-based chemotherapy in Chinese Han populations. Two of these SNPs, rs7629386 and rs3850370, could also be markers for survival among Caucasian patients. ©2012 AACR. Source

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