Kexin Chen

Publications (49)326.78 Total impact

• Source

  Available from: Jiajun Shi

  Article: Common genetic determinants of breast-cancer risk in East Asian women: a collaborative study of 23 637 breast cancer cases and 25 579 controls.

  Wei Zheng, Ben Zhang, Qiuyin Cai, Hyuna Sung, Kyriaki Michailidou, Jiajun Shi, Ji-Yeob Choi, Jirong Long, Joe Dennis, Manjeet K Humphreys, [......], Aiko Sueta, Mi Kyung Kim, Ui Soon Khoo, Motoki Iwasaki, Paul D P Pharoah, Wanqing Wen, Per Hall, Xiao-Ou Shu, Douglas F Easton, Daehee Kang
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  ABSTRACT: In a consortium including 23 637 breast cancer patients and 25 579 controls of East Asian ancestry, we investigated 70 single-nucleotide polymorphisms (SNPs) in 67 independent breast cancer susceptibility loci recently identified by genome-wide association studies (GWASs) conducted primarily in European-ancestry populations. SNPs in 31 loci showed an association with breast cancer risk at P < 0.05 in a direction consistent with that reported previously. Twenty-one of them remained statistically significant after adjusting for multiple comparisons with the Bonferroni-corrected significance level of <0.0015. Eight of the 70 SNPs showed a significantly different association with breast cancer risk by estrogen receptor (ER) status at P < 0.05. With the exception of rs2046210 at 6q25.1, the seven other SNPs showed a stronger association with ER-positive than ER-negative cancer. This study replicated all five genetic risk variants initially identified in Asians and provided evidence for associations of breast cancer risk in the East Asian population with nearly half of the genetic risk variants initially reported in GWASs conducted in European descendants. Taken together, these common genetic risk variants explain ∼10% of excess familial risk of breast cancer in Asian populations.
  Human Molecular Genetics 03/2013; · 7.64 Impact Factor
• Article: Integrated Analyses Identify a Master MicroRNA Regulatory Network for the Mesenchymal Subtype in Serous Ovarian Cancer.

  Da Yang, Yan Sun, Limei Hu, Hong Zheng, Ping Ji, Chad V Pecot, Yanrui Zhao, Sheila Reynolds, Hanyin Cheng, Rajesha Rupaimoole, David Cogdell, Matti Nykter, Russell Broaddus, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Jinsong Liu, Ilya Shmulevich, Anil K Sood, Kexin Chen, Wei Zhang
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  ABSTRACT: Integrated genomic analyses revealed a miRNA-regulatory network that further defined a robust integrated mesenchymal subtype associated with poor overall survival in 459 cases of serous ovarian cancer (OvCa) from The Cancer Genome Atlas and 560 cases from independent cohorts. Eight key miRNAs, including miR-506, miR-141, and miR-200a, were predicted to regulate 89% of the targets in this network. Follow-up functional experiments illustrate that miR-506 augmented E-cadherin expression, inhibited cell migration and invasion, and prevented TGFβ-induced epithelial-mesenchymal transition by targeting SNAI2, a transcriptional repressor of E-cadherin. In human OvCa, miR-506 expression was correlated with decreased SNAI2 and VIM, elevated E-cadherin, and beneficial prognosis. Nanoparticle delivery of miR-506 in orthotopic OvCa mouse models led to E-cadherin induction and reduced tumor growth.
  Cancer cell 02/2013; 23(2):186-99. · 25.29 Impact Factor
• Article: The tumorigenic FGFR3-TACC3 gene fusion escapes miR-99a regulation in glioblastoma.

  Brittany C Parker, Matti J Annala, David E Cogdell, Kirsi J Granberg, Yan Sun, Ping Ji, Xia Li, Joy Gumin, Hong Zheng, Limei Hu, [......], Hannu Haapasalo, Tapio Visakorpi, Xiuping Liu, Chang-Gong Liu, Raymond Sawaya, Gregory N Fuller, Kexin Chen, Frederick L Lang, Matti Nykter, Wei Zhang
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  ABSTRACT: Fusion genes are chromosomal aberrations that are found in many cancers and can be used as prognostic markers and drug targets in clinical practice. Fusions can lead to production of oncogenic fusion proteins or to enhanced expression of oncogenes. Several recent studies have reported that some fusion genes can escape microRNA regulation via 3'-untranslated region (3'-UTR) deletion. We performed whole transcriptome sequencing to identify fusion genes in glioma and discovered FGFR3-TACC3 fusions in 4 of 48 glioblastoma samples from patients both of mixed European and of Asian descent, but not in any of 43 low-grade glioma samples tested. The fusion, caused by tandem duplication on 4p16.3, led to the loss of the 3'-UTR of FGFR3, blocking gene regulation of miR-99a and enhancing expression of the fusion gene. The fusion gene was mutually exclusive with EGFR, PDGFR, or MET amplification. Using cultured glioblastoma cells and a mouse xenograft model, we found that fusion protein expression promoted cell proliferation and tumor progression, while WT FGFR3 protein was not tumorigenic, even under forced overexpression. These results demonstrated that the FGFR3-TACC3 gene fusion is expressed in human cancer and generates an oncogenic protein that promotes tumorigenesis in glioblastoma.
  The Journal of clinical investigation 01/2013; · 15.39 Impact Factor
• Article: Gene-Environment Interactions for Breast Cancer Risk Among Chinese Women: A Report From the Shanghai Breast Cancer Genetics Study.

  Haixin Li, Alicia Beeghly-Fadiel, Wanqing Wen, Wei Lu, Yu-Tang Gao, Yong-Bing Xiang, Qiuyin Cai, Jirong Long, Jiajun Shi, Kexin Chen, Ying Zheng, Xiao Ou Shu, Wei Zheng
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  ABSTRACT: Genome-wide association studies have identified approximately 20 susceptibility loci for breast cancer. A cumulative genetic risk score (GRS) was constructed from 10 variants with replicated associations among participants of the Shanghai Breast Cancer Genetics Study (Shanghai, China, 1996-1998 and 2002-2005). Interactions between the GRS and 11 breast cancer risk factors were evaluated. Among the 6,408 study participants, no evidence of effect modification was found with the GRS for age at menarche, age at menopause, age at first live birth/parity, total months of breastfeeding, family history of breast cancer, history of benign breast disease, hormone replacement therapy, body mass index, waist/hip ratio, or regular physical activity. The effect of the GRS was least homogeneous by duration of menstruation; further analysis indicated a nominally significant interaction with one genetic variant. The mitochondrial ribosomal protein S30 gene (MRPS30) rs10941679 was associated with breast cancer risk only among women with more than 30 years of menstruation (odds ratio = 1.15, 95% confidence interval: 1.05, 1.26). Although this multiplicative interaction reached a nominal significance level (P = 0.037), it did not withstand correction for multiple comparisons. In conclusion, this study revealed no apparent interactions between genome-wide association study-identified genetic variants and breast cancer risk factors in the etiology of this common cancer.Abbreviations: CI, confidence interval; GRS, genetic risk score; OR, odds ratio; SNP, single nucleotide polymorphism.
  American journal of epidemiology 12/2012; · 5.59 Impact Factor
• Source

  Available from: Keitaro Matsuo

  Article: Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia.

  Qing Lan, Chao A Hsiung, Keitaro Matsuo, Yun-Chul Hong, Adeline Seow, Zhaoming Wang, H Dean Hosgood, Kexin Chen, Jiu-Cun Wang, Nilanjan Chatterjee, [......], Hsien-Chih Lin, Tangchun Wu, Yi-Long Wu, Pan-Chyr Yang, Baosen Zhou, Min-Ho Shin, Joseph F Fraumeni, Dongxin Lin, Stephen J Chanock, Nathaniel Rothman
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  ABSTRACT: To identify common genetic variants that contribute to lung cancer susceptibility, we conducted a multistage genome-wide association study of lung cancer in Asian women who never smoked. We scanned 5,510 never-smoking female lung cancer cases and 4,544 controls drawn from 14 studies from mainland China, South Korea, Japan, Singapore, Taiwan and Hong Kong. We genotyped the most promising variants (associated at P < 5 × 10(-6)) in an additional 1,099 cases and 2,913 controls. We identified three new susceptibility loci at 10q25.2 (rs7086803, P = 3.54 × 10(-18)), 6q22.2 (rs9387478, P = 4.14 × 10(-10)) and 6p21.32 (rs2395185, P = 9.51 × 10(-9)). We also confirmed associations reported for loci at 5p15.33 and 3q28 and a recently reported finding at 17q24.3. We observed no evidence of association for lung cancer at 15q25 in never-smoking women in Asia, providing strong evidence that this locus is not associated with lung cancer independent of smoking.
  Nature Genetics 11/2012; · 35.53 Impact Factor
• Article: Cancer Genome Sequencing: Understanding Malignancy as a Disease of the Genome, its Conformation, and its Evolution.

  Lalit R Patel, Matti Nykter, Kexin Chen, Wei Zhang
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  ABSTRACT: Advances in cancer genomics have been propelled by the steady evolution of molecular profiling technologies. Over the past decade, high-throughput sequencing technologies have matured to the point necessary to support disease-specific shotgun sequencing. This has compelled whole-genome sequencing studies across a broad panel of malignancies. The emergence of high-throughput sequencing technologies has inspired new chemical and computational techniques enabling interrogation of cancer-specific genomic and transcriptomic variants, previously unannotated genes, and chromatin structure. Finally, recent progress in single-cell sequencing holds great promise for studies interrogating the consequences of tumor evolution in cancers presenting with genomic heterogeneity.
  Cancer letters 10/2012; · 4.86 Impact Factor
• Article: Association between Single Nucleotide Polymorphisms of the BRAF Gene and Papillary Thyroid Carcinoma in a Chinese Population.

  Qiang Zhang, Fangfang Song, Hong Zheng, Xiaoling Zhu, Fengju Song, Xiaofeng Yao, Lun Zhang, Kexin Chen
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  ABSTRACT: Background：Papillary thyroid cancer (PTC) is a common malignancy that frequently harbours a high prevalence of somatic mutations in the oncogenic BRAF gene. As a novel prognostic molecular marker, this gene has been paid much attention in recent years for its potential utility in the risk prognosis and management of PTC. However, the contribution of the germline variants in this gene to PTC remains unclear. The study herein was aimed to investigate the potential association between the inherited BRAF variants and PTC based on a case-control study. Methods：We selected 4 single nucleotide polymorphisms (SNPs) and took a systematic step to interrogate whether these SNPs of BRAF is associated with PTC risk by genotyping these SNPs from 368 PTC patients and 564 healthy controls. Results：No differences were observed in the genotypic and allelic frequencies between cases and controls for the four SNPs, neither did the association between BRAF SNPs and overall risk of PTC. While after stratification, we found a significantly increased risk of PTC attributed to SNP rs3748093, rs17161747, and rs1042179 variants, for those with age < 45 years and non-drinkers, those with a family history of cancer, and smokers, respectively. Further, in the PTC cases, those carrying rs3748093 variant seemed to be less susceptible to developing lymph node metastasis but more easily to suffer from PTC at an earlier age (< 45 years). Conclusions：These preliminary results may provide evidence for the involvement of the common genetic variants scattered throughout BRAF oncogene in the prediction of PTC onset and progression. In the future enlarging number of samples and performing functional study in this gene may help to validate whether the association really exists.
  Thyroid: official journal of the American Thyroid Association 09/2012; · 2.60 Impact Factor
• Article: Association analyses identify multiple new lung cancer susceptibility loci and their interactions with smoking in the Chinese population.

  Jing Dong, Zhibin Hu, Chen Wu, Huan Guo, Baosen Zhou, Jiachun Lv, Daru Lu, Kexin Chen, Yongyong Shi, Minjie Chu, [......], Yuxia Zhao, Haibo Zhang, Ying Yan, Christopher I Amos, Feng Chen, Wen Tan, Li Jin, Tangchun Wu, Dongxin Lin, Hongbing Shen
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  ABSTRACT: To find additional susceptibility loci for lung cancer, we tested promising associations from our previous genome-wide association study (GWAS) of lung cancer in the Chinese population in an extended validation sample size of 7,436 individuals with lung cancer (cases) and 7,483 controls. We found genome-wide significant (P < 5.0 × 10(-8)) evidence for three additional lung cancer susceptibility loci at 10p14 (rs1663689, close to GATA3, P = 2.84 × 10(-10)), 5q32 (rs2895680 in PPP2R2B-STK32A-DPYSL3, P = 6.60 × 10(-9)) and 20q13.2 (rs4809957 in CYP24A1, P = 1.20 × 10(-8)). We also found consistent associations for rs247008 at 5q31.1 (IL3-CSF2-P4HA2, P = 7.68 × 10(-8)) and rs9439519 at 1p36.32 (AJAP1-NPHP4, P = 3.65 × 10(-6)). Four of these loci showed evidence for interactions with smoking dose (P = 1.72 × 10(-10), P = 5.07 × 10(-3), P = 6.77 × 10(-3) and P = 4.49 × 10(-2) for rs2895680, rs4809957, rs247008 and rs9439519, respectively). These results advance our understanding of lung cancer susceptibility and highlight potential pathways that integrate genetic variants and smoking in the development of lung cancer.
  Nature Genetics 07/2012; 44(8):895-9. · 35.53 Impact Factor
• Article: Descriptive epidemiology of female breast cancer in Tianjin, China

  Kexin Chen, Min He, Shufen Dong, Jifang Wang
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  ABSTRACT: ObjectiveTo observe trends in the changes of incidence and mortality of female breast cancer patients in Tianjin, and evaluate the effect of these trends on prevention. MethodsA method of descriptive epidemiology was used to comprehensively study the status of lemale breast cancer in Tianjin. ResultsFrom 1981 to 2000, the incidence rate of breast cancer in Tianjin had been increasing at the speed of 1.8 % annually, whereas (he peak of the age -adjusted incidence and mortality rate expressed a mild declining trend. Follow-up study indicated that 3 and 5-year survival rates improved in various degrees ConclusionEarly detection and diagnosis of breast cancer are very important to both increasing survival and lowering mortality from breast cancer. Preventive efforts should be promoted for women who are at high risk for breast cancer.
  Chinese Journal of Clinical Oncology 04/2012; 1(3):207-210.
• Article: Prostate stem cell antigen polymorphisms and susceptibility to gastric cancer: a systematic review and meta-analysis.

  Tao Wang, Lina Zhang, Haixin Li, Bangmao Wang, Kexin Chen
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  ABSTRACT: Many studies have reported that prostate stem cell antigen (PSCA) polymorphisms (rs2294008 and/or 2976392) are significantly associated with gastric cancer (GC) risk, although the published results are inconsistent. We conducted a systematic review and meta-analysis for relevant literatures to quantitatively evaluate the relationship between PSCA polymorphisms and GC susceptibility. Extensive searches were conducted in three databases up to November 1, 2011. ORs and 95% CIs were used to assess the strength of the associations. The data were further stratified by ethnicity, histopathology, subsite, and study design. All of the associations were evaluated with dominant model and recessive model, respectively. Heterogeneity and publication bias were also assessed by Q test, I(2), and funnel plot accordingly. Nine articles including 11 case-control data sets were included, with 10,746 GC cases and 9,158 controls for rs2294008 and 6,060 cases and 4,824 controls for rs2976392. The results showed that risk allele carriers were significantly associated with GC risk compared with nonrisk allele homozygotes. In stratification analyses, these associations remained significant for majority of subgroups except for Caucasians and noncardia tumor in dominant model, and cardia tumor in both dominant and recessive model. Random model was used when heterogeneity among studies was detected. No publication bias was observed. The two loci of PSCA (rs2294008 and rs2976392) were both significantly associated with GC susceptibility and in linkage disequilibrium. More prospective studies on PSCA polymorphisms at multicenters with sufficient sample size and less heterogeneity will be needed for further validations.
  Cancer Epidemiology Biomarkers &amp Prevention 03/2012; 21(5):843-50. · 4.12 Impact Factor
• Article: Genetic variant in TP63 on locus 3q28 is associated with risk of lung adenocarcinoma among never-smoking females in Asia.

  H Dean Hosgood, Wen-Chang Wang, Yun-Chul Hong, Jiu-Cun Wang, Kexin Chen, I-Shou Chang, Chien-Jen Chen, Daru Lu, Zhihua Yin, Chen Wu, [......], Fang-Yu Tsai, Pan-Chyr Yang, Joseph F Fraumeni, Adeline Seow, Dongxin Lin, Baosen Zhou, Stephen Chanock, Chao Agnes Hsiung, Nathaniel Rothman, Qing Lan
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  ABSTRACT: A recent genome-wide association study (GWAS) of subjects from Japan and South Korea reported a novel association between the TP63 locus on chromosome 3q28 and risk of lung adenocarcinoma (p = 7.3 × 10(-12)); however, this association did not achieve genome-wide significance (p ≤ 10(-7)) among never-smoking males or females. To determine if this association with lung cancer risk is independent of tobacco use, we genotyped the TP63 SNPs reported by the previous GWAS (rs10937405 and rs4488809) in 3,467 never-smoking female lung cancer cases and 3,787 never-smoking female controls from 10 studies conducted in Taiwan, Mainland China, South Korea, and Singapore. Genetic variation in rs10937405 was associated with risk of lung adenocarcinoma [n = 2,529 cases; p = 7.1 × 10(-8); allelic risk = 0.80, 95% confidence interval (CI) = 0.74-0.87]. There was also evidence of association with squamous cell carcinoma of the lung (n = 302 cases; p = 0.037; allelic risk = 0.82, 95% CI = 0.67-0.99). Our findings provide strong evidence that genetic variation in TP63 is associated with the risk of lung adenocarcinoma among Asian females in the absence of tobacco smoking.
  Human Genetics 02/2012; 131(7):1197-203. · 5.07 Impact Factor
• Source

  Available from: Ui Soon Khoo

  Article: Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer.

  Jirong Long, Qiuyin Cai, Hyuna Sung, Jiajun Shi, Ben Zhang, Ji-Yeob Choi, Wanqing Wen, Ryan J Delahanty, Wei Lu, Yu-Tang Gao, [......], Yoshio Kasuga, Sei-Hyun Ahn, Han Sung Kang, Kelvin Y K Chan, Hiroji Iwata, Shoichiro Tsugane, Chun Li, Xiao-Ou Shu, Dae-Hee Kang, Wei Zheng
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  ABSTRACT: Genetic factors play an important role in the etiology of both sporadic and familial breast cancer. We aimed to discover novel genetic susceptibility loci for breast cancer. We conducted a four-stage genome-wide association study (GWAS) in 19,091 cases and 20,606 controls of East-Asian descent including Chinese, Korean, and Japanese women. After analyzing 690,947 SNPs in 2,918 cases and 2,324 controls, we evaluated 5,365 SNPs for replication in 3,972 cases and 3,852 controls. Ninety-four SNPs were further evaluated in 5,203 cases and 5,138 controls, and finally the top 22 SNPs were investigated in up to 17,423 additional subjects (7,489 cases and 9,934 controls). SNP rs9485372, near the TGF-β activated kinase (TAB2) gene in chromosome 6q25.1, showed a consistent association with breast cancer risk across all four stages, with a P-value of 3.8×10(-12) in the combined analysis of all samples. Adjusted odds ratios (95% confidence intervals) were 0.89 (0.85-0.94) and 0.80 (0.75-0.86) for the A/G and A/A genotypes, respectively, compared with the genotype G/G. SNP rs9383951 (P = 1.9×10(-6) from the combined analysis of all samples), located in intron 5 of the ESR1 gene, and SNP rs7107217 (P = 4.6×10(-7)), located at 11q24.3, also showed a consistent association in each of the four stages. This study provides strong evidence for a novel breast cancer susceptibility locus represented by rs9485372, near the TAB2 gene (6q25.1), and identifies two possible susceptibility loci located in the ESR1 gene and 11q24.3, respectively.
  PLoS Genetics 02/2012; 8(2):e1002532. · 8.69 Impact Factor
• Article: Genomic and molecular characterization of malignant peripheral nerve sheath tumor identifies the IGF1R pathway as a primary target for treatment.

  Jilong Yang, Antti Ylipää, Yan Sun, Hong Zheng, Kexin Chen, Matti Nykter, Jonathan Trent, Nancy Ratner, Dina C Lev, Wei Zhang
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  ABSTRACT: Malignant peripheral nerve sheath tumor (MPNST) is a rare sarcoma that lacks effective therapeutic strategies. We gain insight into the most recurrent genetically altered pathways with the purpose of scanning possible therapeutic targets. We conducted a microarray-based comparative genomic hybridization profiling of two cohorts of primary MPNST tissue samples including 25 patients treated at The University of Texas MD Anderson Cancer Center and 26 patients from Tianjin Cancer Hospital. Immunohistochemistry (IHC) and cell biology detection and validation were carried out on human MPNST tissues and cell lines. Genomic characterization of 51 MPNST tissue samples identified several frequently amplified regions harboring 2,599 genes and regions of deletion including 4,901 genes. At the pathway level, we identified a significant enrichment of copy number-altering events in the insulin-like growth factor 1 receptor (IGF1R) pathway, including frequent amplifications of the IGF1R gene itself. To validate the IGF1R pathway as a potential target in MPNSTs, we first confirmed that high IGF1R protein correlated with worse tumor-free survival in an independent set of samples using IHC. Two MPNST cell lines (ST88-14 and STS26T) were used to determine the effect of attenuating IGF1R. Inhibition of IGF1R in ST88-14 cells using siRNAs or an IGF1R inhibitor, MK-0646, led to significant decreases in cell proliferation, invasion, and migration accompanied by attenuation of the PI3K/AKT and mitogen-activated protein kinase pathways. These integrated genomic and molecular studies provide evidence that the IGF1R pathway is a potential therapeutic target for patients with MPNST.
  Clinical Cancer Research 12/2011; 17(24):7563-73. · 7.74 Impact Factor
• Article: Genome-wide association study identifies breast cancer risk variant at 10q21.2: results from the Asia Breast Cancer Consortium.

  Qiuyin Cai, Jirong Long, Wei Lu, Shimian Qu, Wanqing Wen, Daehee Kang, Ji-Young Lee, Kexin Chen, Hongbing Shen, Chen-Yang Shen, [......], Guoliang Li, Shawn Levy, Bo Huang, Jiajun Shi, Ryan Delahanty, Ying Zheng, Chun Li, Yu-Tang Gao, Xiao-Ou Shu, Wei Zheng
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  ABSTRACT: Although approximately 20 common genetic susceptibility loci have been identified for breast cancer risk through genome-wide association studies (GWASs), genetic risk variants reported to date explain only a small fraction of heritability for this common cancer. We conducted a four-stage GWAS including 17 153 cases and 16 943 controls among East-Asian women to search for new genetic risk factors for breast cancer. After analyzing 684 457 SNPs in 2062 cases and 2066 controls (Stage I), we selected for replication among 5969 Chinese women (4146 cases and 1823 controls) the top 49 SNPs that had neither been reported previously nor were in strong linkage disequilibrium with reported SNPs (Stage II). Three SNPs were further evaluated in up to 13 152 Chinese and Japanese women (6436 cases and 6716 controls) (Stage III). Finally, two SNPs were evaluated in 10 847 Korean women (4509 cases and 6338 controls) (Stage IV). SNP rs10822013 on chromosome 10q21.2, located in the zinc finger protein 365 (ZNF365) gene, showed a consistent association with breast cancer risk in all four stages with a combined per-risk allele odds ratio of 1.10 (95% CI: 1.07-1.14) (P-value for trend = 5.87 × 10(-9)). In vitro electrophoretic mobility shift assays demonstrated the potential functional significance of rs10822013. Our results strongly implicate rs10822013 at 10q21.2 as a genetic risk variant for breast cancer among East-Asian women.
  Human Molecular Genetics 09/2011; 20(24):4991-9. · 7.64 Impact Factor
• Source

  Available from: Fengju Song

  Article: Functional SNP in the microRNA-367 binding site in the 3'UTR of the calcium channel ryanodine receptor gene 3 (RYR3) affects breast cancer risk and calcification.

  Lina Zhang, Yuexin Liu, Fengju Song, Hong Zheng, Limei Hu, Hong Lu, Peifang Liu, Xishan Hao, Wei Zhang, Kexin Chen
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  ABSTRACT: We have evaluated and provided evidence that the ryanodine receptor 3 gene (RYR3), which encodes a large protein that forms a calcium channel, is important for the growth, morphology, and migration of breast cancer cells. A putative binding site for microRNA-367 (miR-367) exists in the 3'UTR of RYR3, and a genetic variant, rs1044129 A→G, is present in this binding region. We confirmed that miR-367 regulates the expression of a reporter gene driven by the RYR3 3'UTR and that the regulation was affected by the RYR3 genotype. A thermodynamic model based on base pairing and the secondary structure of the RYR3 mRNA and miR-367 miRNA showed that miR-367 had a higher binding affinity for the A genotype than for the G genotype. The rs1044129 SNP was genotyped in 1,532 breast cancer cases and 1,600 healthy Chinese women. The results showed that compared with the AA genotype, G was a risk genotype for breast cancer development and was also associated with breast cancer calcification and poor survival. Thus, rs1044129 is a unique SNP that resides in a miRNA-gene regulatory loop that affects breast cancer risk, calcification, and survival.
  Proceedings of the National Academy of Sciences 08/2011; 108(33):13653-8. · 9.68 Impact Factor
• Source

  Available from: InTech

  Chapter: Combustion Synthesis of Ceramic Powders with Controlled Grain Morphologies

  Guanghua Liu, Jiangtao Li, Kexin Chen
  08/2011; , ISBN: 978-953-307-505-1
• Article: NGAL expression is elevated in both colorectal adenoma-carcinoma sequence and cancer progression and enhances tumorigenesis in xenograft mouse models.

  Yan Sun, Kenji Yokoi, Hui Li, Jun Gao, Limei Hu, Ben Liu, Kexin Chen, Stanley R Hamilton, Dominic Fan, Baocun Sun, Wei Zhang
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  ABSTRACT: There is growing evidence implicating that neutrophil gelatinase-associated lipocalin (NGAL) plays a role in the development and progression of cancers. However, the effect of NGAL in colorectal carcinoma (CRC) has not been clearly elucidated. In this study, we investigated the role of NGAL in the tumorigenesis and progression of CRC and evaluated the clinical value of NGAL expression. We examined NGAL expression in 526 colorectal tissue samples, including 53 sets of matched specimens (histologically normal mucosa, adenomas, and carcinomas) using immunohistochemical analysis. In CRCs, correlations between NGAL expression and clinicopathologic parameters were analyzed, and survival analysis was conducted. The role of NGAL was further tested using mouse xenograft models. NGAL expression was elevated during the colorectal adenoma-carcinoma sequence both among the 526 cases (r(s) = 0.66, P < 0.001) and in the 53 sets of matched specimens (r(s) = 0.60, P < 0.001). In CRCs, NGAL expression was associated with cancer stage (P = 0.041) and tumor recurrence in stage II patients (P = 0.037). Survival analysis revealed that NGAL expression was an independent prognostic factor for overall survival (HR = 1.84, P = 0.004) and for disease-free survival of stage II patients (HR = 5.88, P = 0.021). In mouse models, the xenografts in cecum and spleen were heavier and more numerous in the group injected with NGAL-overexpressing CRC cells (P < 0.05). NGAL overexpression may promote the tumorigenesis and progression of CRC. Detecting NGAL expression in tumor tissues may be useful for evaluating prognosis of patients with CRC.
  Clinical Cancer Research 05/2011; 17(13):4331-40. · 7.74 Impact Factor
• Article: Genotypes and phenotypes of IGF-I and IGFBP-3 in breast tumors among Chinese women.

  Biyun Qian, Hong Zheng, Herbert Yu, Kexin Chen
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  ABSTRACT: The relationship between IGF genotypes and phenotypes in breast tumors and their associations with breast cancer risk remain to be elucidated. Such information is especially scarce in Chinese women. To evaluate IGF-I and IGFBP-3 genotypes in relation to their phenotypes in local breast tissues and in association with breast cancer risk, we conducted a case-control study among Chinese women. The study recruited 403 breast cancer patients and 403 age-matched controls. Four single nucleotide polymorphisms (SNP) in the IGF-I gene (rs1520220, rs2946834, rs2195239, and rs7965399) and two SNPs of the IGFBP-3 gene (rs2854746 and rs2960436) with known correlations with their phenotypes in the circulation were genotyped using TaqMan assays. Fresh tumor samples from the same patients were analyzed with immunoassays for protein concentrations of IGF-I and IGFBP-3. Associations of breast cancer with these SNPs were examined using unconditional logistic regression. Correlations between IGF genotypes and phenotypes were determined with Wilcoxon rank-sum test. Of the six selected SNPs, only one IGF-I SNP (rs7965399) was associated with breast cancer risk in a recessive model (OR = 1.86; 95% CI: 1.04-3.32), and the association was more evident in patients who had menopause under age 50 or ER negative tumors. No associations were found between breast cancer and other three IGF-I and two IGFBP-3 SNPs. Patients with variant IGF-I or wild IGFBP-3 genotypes had higher peptide levels of IGF-I compared to those with wild IGF-I or variant IGFBP-3 genotypes. The selected IGF-I and IGFBP-3 SNPs did not show any strong evidence for being associated with breast cancer risk, but the genotypes were correlated with IGF-I phenotypes in tumor samples, suggesting possible influences of these SNPs on IGF-I activity in local tissues.
  Breast Cancer Research and Treatment 05/2011; 130(1):217-26. · 4.43 Impact Factor
• Article: Genetic amplification of the vascular endothelial growth factor (VEGF) pathway genes, including VEGFA, in human osteosarcoma.

  Jilong Yang, Da Yang, Yan Sun, Baocun Sun, Guowen Wang, Jonathan C Trent, Dejka M Araujo, Kexin Chen, Wei Zhang
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  ABSTRACT: Osteosarcoma is the most common primary tumor of bone. It is a highly vascular and extremely destructive malignancy that mainly affects children and young adults. The authors conducted microarray-based comparative genomic hybridization (aCGH) and pathway analyses to gain a systemic view of pathway alterations in the genetically altered genes. Recurrent amplified and deleted genes that were detected by aCGH were subjected to an analysis based on the Kyoto Encyclopedia of Genes and Genomes to identify the altered pathways. Among the enriched pathways, vascular endothelial growth factor (VEGF) pathway genes collectively were amplified, and alterations of this pathway were validated by fluorescence in situ hybridization (FISH) and immunohistochemistry analyses in 58 formalin-fixed, paraffin-embedded osteosarcoma archival tissues that had clinical follow-up information. The pathway enrichment analyses of the aCGH data revealed that VEGF pathway genes, including the VEGFA gene itself, were amplified significantly in osteosarcoma. Genetic amplification of the VEGFA gene, both focally and in larger fragment, was validated by FISH analysis. It is noteworthy that amplification of the VEGFA gene and elevated expression of the VEGFA protein were associated significantly with microvascular density and adverse tumor-free survival in patients with osteosarcoma. The authors report for the first time that VEGF pathway genes, including the VEGFA gene, are amplified in osteosarcoma. Amplification of the VEGFA gene is not only an important mechanism for elevated VEGFA protein expression but also is a poor prognostic factor for tumor-free survival. Combined classification of VEGFA gene amplification and positive VEGFA protein expression may provide a more accurate stratification method of selecting anti-VEGF therapy for patients with osteosarcoma.
  Cancer 04/2011; 117(21):4925-38. · 4.77 Impact Factor
• Article: Genetic variants at the miR-124 binding site on the cytoskeleton-organizing IQGAP1 gene confer differential predisposition to breast cancer.

  Hong Zheng, Fengju Song, Lina Zhang, Da Yang, Ping Ji, Yingmei Wang, Maria Almeida, George A Calin, Xishan Hao, Qingyi Wei, Wei Zhang, Kexin Chen
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  ABSTRACT: IQGAP1 knockout mice develop gastric cancer, but the IQGAP1 protein is associated with some advanced-stage human cancers. IQGAP1 expression is regulated by a microRNA, miR-124, through a binding site at the 3'-untranslated region, where a single nucleotide polymorphism (SNP) exists in the core binding region. We asked whether IQGAP1 expression is associated with breast cancer development and whether genetic variants at the miR-124 binding site are important. We genotyped the IQGAP1 SNP rs1042538 A/T in 1,541 breast cancer cases and 1,598 controls and analyzed the frequency of the variant and interactions with major risk factors in these populations. We also measured the expression of IQGAP1 at both mRNA and protein levels in different IQGAP1 genotypes. The IQGAP1 TT genotype, compared with the AA genotype, was associated with a significantly lower risk of developing breast cancer [P=0.049, odds ratio (OR), 0.78; 95% confidence interval (CI), 0.61-0.99]. In case-only analyses, the TT, compared with the AA, genotype was associated with progesterone receptor-positive subjects (OR, 1.35; 95% CI, 1.00-1.83). The expression levels of IQGAP1 protein were significantly higher in the TT genotype compated to the AA genotype. The presence of SNPs at the miR-124 binding site may be a marker for predicting breast cancer risk and prognosis.
  International Journal of Oncology 04/2011; 38(4):1153-61. · 2.40 Impact Factor