Combined Effects of Six Cytokine Gene Polymorphisms and SNP-SNP Interactions on Hepatocellular Carcinoma Risk in Southern Guangxi, China

Bei, Chun-Hua,Bai, Hua,Yu, Hong-Ping,Yang, Yan,Liang, Qing-Qing,Deng, Ying-Ying,Tan, Sheng-Kui,Qiu, Xiao-Qiang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.16

Cytokine gene single nucleotide polymorphisms (SNPs) are involved in the genesis and progression of hepatocellular carcinoma (HCC). We hypothesized that combined effects of cytokine gene SNPs and SNP-SNP interactions are associated with HCC risk. Six SNPs in cytokine genes (IL-2, IFN-${\gamma}$, IL-$1{\beta}$, IL-6, and IL-10) were genotyped in a study of 720 Chinese HCC cases and 784 cancer-free controls. Although none of these SNPs individually had a significant effect on the risk of HCC, we found that the combined effects of these six SNPs may contribute to HCC risk (OR=1.821, 95% CI=1.078-3.075). This risk was pronounced among smokers, drinkers, and hepatitis B virus carriers. A SNP-SNP interaction between IL-2-330 and IFN-${\gamma}$-1615 was associated with an increased HCC risk (OR=1.078, 95% CI=1.022-1.136). In conclusion, combined effects of SNPs and SNP-SNP interactions in cytokine genes may contribute to HCC risk.

Comparative Serum Proteomic Analysis of Serum Diagnosis Proteins of Colorectal Cancer Based on Magnetic Bead Separation and MALDI-TOF Mass Spectrometry

Deng, Bao-Guo,Yao, Jin-Hua,Liu, Qing-Yin,Feng, Xian-Jun,Liu, Dong,Zhao, Li,Tu, Bin,Yang, Fan Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.10

Background: At present, the diagnosis of colorectal cancer (CRC) requires a colorectal biopsy which is an invasive procedure. We undertook this pilot study to develop an alternative method and potential new biomarkers for diagnosis, and validated a set of well-integrated tools called ClinProt to investigate the serum peptidome in CRC patients. Methods: Fasting blood samples from 67 patients diagnosed with CRC by histological diagnosis, 55 patients diagnosed with colorectal adenoma by biopsy, and 65 healthy volunteers were collected. Division was into a model construction group and an external validation group randomly. The present work focused on serum proteomic analysis of model construction group by ClinProt Kit combined with mass spectrometry. This approach allowed construction of a peptide pattern able to differentiate the studied populations. An external validation group was used to verify the diagnostic capability of the peptidome pattern blindly. An immunoassay method was used to determine serum CEA of CRC and controls. Results: The results showed 59 differential peptide peaks in CRC, colorectal adenoma and health volunteers. A genetic algorithm was used to set up the classification models. Four of the identified peaks at m/z 797, 810, 4078 and 5343 were used to construct peptidome patterns, achieving an accuracy of 100% (> CEA, P<0.05). Furthermore, the peptidome patterns could differentiate the validation group with high accuracy close to 100%. Conclusions: Our results showed that proteomic analysis of serum with MALDI-TOF MS is a fast and reproducible approach, which may provide a novel approach to screening for CRC.

A prospective randomized multicenter trial for lymphadenectomy in early- stage ovarian cancer: LOVE study

Ting Deng,Kaijiang Liu,Liang Chen,Xiao-jun Chen,Hua Wen Li,Hongyan Guo,Huijiao Zhang,Libing Xiang,Xin Feng,Xiaoyu Wang,Hextan Y. S. Ngan,Jianguo Zhao,Dongling Zou,Qing Liu,Jihong Liu 대한부인종양학회 2023 Journal of Gynecologic Oncology Vol.34 No.3

Background: The Lymphadenectomy in Ovarian Neoplasms (LION) study revealed that systemic lymphadenectomy did not bring survival benefit for advanced ovarian cancer patients with clinically normal lymph nodes and was associated with a higher incidence of operative complications. However, there is no consensus on whether lymphadenectomy has survival benefit or not in early epithelial ovarian cancer (EOC). Methods: We designed the LOVE study, a multicenter, randomized controlled, phase III trial to compare the efficacy and safety of comprehensive staging surgery with or without lymphadenectomy in stages IA-IIB EOC and fallopian tube carcinomas (FTC). The hypothesis is that the oncological outcomes provided by comprehensive staging surgery without lymphadenectomy are non-inferior to those of conventional completion staging surgery in early-stage EOC and FTC patients who have indications for post-operative adjuvant chemotherapy. Patients assigned to experimental group will undergo comprehensive staging surgery, but lymphadenectomy. Patients assigned to comparative group will undergo completion staging surgery including systematic pelvic and para-aortic lymphadenectomy. All subjects will receive 3–6 cycles of standard adjuvant chemotherapy. Major inclusion criteria are pathologic confirmed stage IA-IIB EOC or FTC, and patients have indications for adjuvant chemotherapy either confirmed by intraoperative fast frozen section or previous pathology after an incomplete staging surgery. Major exclusion criteria are non-epithelial tumors and low-grade serous carcinoma. Patients with severe rectum involvement which lead to partial rectum resection will be excluded. The sample size is 656 subjects. Primary endpoint is disease-free survival.

Synergistic efficacy of LBH and αB-crystallin through inhibiting transcriptional activities of p53 and p21

( Yun Deng ),( Yong Qing Li ),( Xiong Wei Fan ),( Wu Zhou Yuan ),( Hua Ping Xie ),( Xiao Yang Mo ),( Yan Yan ),( Jun Mei Zhou ),( Yue Qun Wang ),( Xian Li Ye ),( Yong Qi Wan ),( Xiu Shan Wu ) 생화학분자생물학회 (구 한국생화학분자생물학회) 2010 BMB Reports Vol.43 No.6

LBH is a transcription factor as a candidate gene for CHD associated with partial trisomy 2p syndrome. To identify potential LBH-interacting partners, a yeast two-hybrid screen using LBH as a bait was performed with a human heart cDNA library. One of the clones identified encodes αB-crystallin. Co-immunoprecipitation and GST pull-down assays showed that LBH interacts with αB-crystallin, which is further confirmed by mammalian two-hybrid assays. Co-localization analysis showed that in COS-7 cells, αB-crystallin that is cytoplasmic alone, accumulates partialy in the nucleus when co-transfected with LBH. Transient transfection assays indicated that overexpression of LBH or αB-crystallin reduced the transcriptional activities of p53 and p21, respectively, Overexpression of both αB-crystallin and LBH together resulted in a stronger repression of the transcriptional activities of p21 and p53. These results showed that the interaction of LBH and αB-crystallin may inhibit synergistically the transcriptional regulation of p53 and p21. [BMB reports 2010; 43(6): 432-437]

QTL mapping and identification of candidate genes for cold tolerance at the germination stage in wild rice

Pan Ying-Hua,Nong Bao-Xuan,Chen Lei,Yang Xing-Hai,Xia Xiu-Zhong,Zhang Zong-Qiong,Qing Dong-Jin,Gao Ju,Huang Cheng-Cui,Li Dan-Ting,Deng Guo-Fu 한국유전학회 2023 Genes & Genomics Vol.45 No.7

Background Cold damage stress significantly affects rice growth (germination and seedling) and causes serious losses in yield in temperate and high-altitude areas around the globe. Objective This study aimed to explore the cold tolerance (CT) locus of rice and create new cold-tolerant germplasm. We constructed a chromosome segment substitution line (CSSL) with strong CT and fine mapped quantitative trait loci (QTLs) associated with CT by performing the whole-genome resequencing of CSSL with phenotypes under cold treatment. Methods A chromosome CSSL, including 271 lines from a cross between the cold-tolerant wild rice Y11 (Oryza rufipogon Griff.) and the cold-sensitive rice variety GH998, was developed to map QTLs conferring CT at the germination stage. The whole-genome resequencing was performed on CSSL for mapping QTLs of associated with CT at the germination stage. Results A high-density linkage map of the CSSLs was developed using the whole-genome resequencing of 1484 bins. The QTL analysis using 615,466 single-nucleotide polymorphisms (SNPs) led to the identification of 2 QTLs related to germination rate at low-temperature on chromosome 8 (qCTG-8) and chromosome 11 (qCTG-11). The qCTG-8 and qCTG-11 explained 14.55% and 14.31% of the total phenotypic variation, respectively. We narrowed down qCTG-8 and qCTG-11 to 195.5 and 78.83-kb regions, respectively. The expression patterns of important candidate genes in different tissues, and of RNA-sequencing (RNA-seq) in CSSLs, were identified based on gene sequences in qCTG-8 and qCTG-11 cold-induced expression analysis. LOC_Os08g01120 and LOC_Os08g01390 were identified as candidate genes in qCTG-8, and LOC_Os11g32880 was identified as a candidate gene in qCTG-11. Conclusions This study demonstrated a general method that could be used to identify useful loci and genes in wild rice and aid in the future cloning of candidate genes of qCTG-8 and qCTG-11. The CSSLs with strong CT were supported for breeding cold-tolerant rice varieties.

Lovastatin derivative dehydrolovastatin ameliorates ulcerative colitis in mice by suppressing NF-κB and inflammatory cytokine expression

Xu Zhang,Qing-Hua Deng,Jian-Hua Deng,Sheng-Ju Wang,Qiu Chen 대한생리학회-대한약리학회 2020 The Korean Journal of Physiology & Pharmacology Vol.24 No.2

Ulcerative colitis (UC) is associated with intestinal immune imbalance and inflammatory response. Because dehydrolovastatin (DLVT), a derivative of lovastatin, has been recently shown to inhibit inflammation and relieve immune arthritis induced by chemical stimuli, we studied its effect and possible mechanism on UC induced by dextran sulfate sodium. The BALB/c mice were classified into six groups: normal control group, model group, DLVT high dose group, DLVT low dose group, salazosulfapyridine (SASP) group and lovastatin (LVT) group. The disease activity indices of UC and pathological changes were investigated. The myeloperoxidase (MPO) activity in colon tissue and inflammatory factors such as IL-6, IL-10, IL-17, and TNF- in the serum were analyzed by ELISA, while the expression of NF-B p65 protein in colon tissue was detected by immunohistochemistry and western blot. DLVT relieved the disease activity indices and pathological damage of the UC mice. Furthermore, DLVT significantly decreased MPO activity and improved the imbalance of inflammatory cytokines through inhibiting the expression of NF-B p65. Meanwhile, the positive drug of SASP has a similar effect to DLVT, but the effect of DLVT in both decreasing IL-17, TNF-, and increasing IL-10 was significantly stronger than that of SASP. These results suggest that DLVT may ameliorates the symptoms of UC.

Prognostic Role of Hypoxic Inducible Factor Expression in Non-small Cell Lung Cancer: A Meta-analysis

Li, Cong,Lu, Hua-Jun,Na, Fei-Fei,Deng, Lei,Xue, Jian-Xin,Wang, Jing-Wen,Wang, Yu-Qing,Li, Qiao-Ling,Lu, You Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.6

Introduction: Reported prognostic roles of hypoxic inducible factor (HIF) expression in non-small cell lung cancer (NSCLC) have varied. This meta-analysis aimed to examine the relationship between HIF expression and clinical outcome in NSCLC patients. Methods: PubMed were used to identify relevant literature with the last report up to December $20^{th}$, 2012. After careful review, survival data were collected from eligible studies. We completed the meta-analysis using Stata statistical software (Version 11) and combined hazard ratio (HR) for overall survival (OS). Subgroup specificity, heterogeneity and publication bias were also assessed. All of the results were verified by two persons to ensure accuracy. Results: Eight studies were finally stepped into this meta-analysis in which seven had available data for HIF-$1{\alpha}$ and three for HIF-$2{\alpha}$. Combined HRs suggested that higher expression of $HIF1{\alpha}$ had a negative impact on NSCLC patient survival (HR=1.50; 95%CI=1.07-2.10; p=0.019). The expression of HIF-$2{\alpha}$ was also relative to a poorer survival (HR=2.02; 95%CI=1.47-2.77; p=0.000). No bias existed in either of the two groups. Conclusion: This study suggests that elevations of HIF-$1{\alpha}$ and HIF-$2{\alpha}$ expression are both associated with poor outcome for patients with NSCLC. The data support further and high quality investigation of HIF expression for predicting poor outcome in patients with NSCLC.

Pan-cancer Analysis of Tumor Mutational Burden and Homologous Recombination DNA Damage Repair Using Targeted Next-Generation Sequencing

Hai-Yun Wang,Ling Deng,Ying-Qing Li,Xiao Zhang,Ya-Kang Long,Xu Zhang,Yan-Fen Feng,Yuan He,Tao Tang,Xin-Hua Yang,Fang Wang 대한암학회 2021 Cancer Research and Treatment Vol.53 No.4

Purpose Current variability in methods for tumor mutational burden (TMB) estimation and reporting demonstrates the urgent need for a homogeneous TMB assessment approach. Here, we compared TMB distributions in different cancer types using two customized targeted panels commonly used in clinical practice. Materials and Methods TMB spectra of 295- and 1021-gene panels in multiple cancer types were compared using targeted next-generation sequencing (NGS). The TMB distributions across a diverse cohort of 2,332 cancer cases were then investigated for their associations with clinical features. Treatment response data were collected for 222 patients who received immune-checkpoint inhibitors (ICIs) and their homologous recombination DNA damage repair (HR-DDR) and programmed death-ligand 1 (PD-L1) expression were additionally assessed and compared with the TMB and response rate. Results The median TMB between gene panels was similar despite a wide range in TMB values. The highest TMB was eight and 10 in patients with squamous cell carcinoma and esophageal carcinoma according to the classification of histopathology and cancer types, respectively. Twenty-three out of 103 patients (22.3%) were HR-DDR–positive and could benefit from ICI therapy; out of those 23 patients, seven patients had high TMB (p=0.004). Additionally, PD-L1 expression was not associated with TMB or treatment response among patients receiving ICIs. Conclusion Targeted NGS assays demonstrated the ability to evaluate TMB in pan-cancer samples as a tool to predict response to ICIs. In addition, TMB integrated with HR-DDR–positive status could be a significant biomarker for predicting ICI response in patients.

LncRNA-IMAT1 Promotes Invasion of Meningiomas by Suppressing KLF4/hsa-miR22-3p/Snai1 Pathway

Tao Zhang,Yu Ge,Daijun Wang,Qin Liu,Shuchen Sun,Lingyang Hua,Jiaojiao Deng,Shihai Luan,Haixia Cheng,Qing Xie,Ye Gong,Tao Zhang 한국분자세포생물학회 2022 Molecules and cells Vol.45 No.6

Malignant meningiomas often show invasive growth that makes complete tumor resection challenging, and they are more prone to recur after radical resection. Invasive meningioma associated transcript 1 (IMAT1) is a long noncoding RNA located on Homo sapiens chromosome 17 that was identified by our team based on absolute expression differences in invasive and non-invasive meningiomas. Our studies indicated that IMAT1 was highly expressed in invasive meningiomas compared with non-invasive meningiomas. In vitro studies showed that IMAT1 promoted meningioma cell invasion through the inactivation of the Krüppel-like factor 4 (KLF4)/hsa-miR22-3p/Snai1 pathway by acting as a sponge for hsa-miR22-3p, and IMAT1 knockdown effectively restored the tumor suppressive properties of KLF4 by preserving its tumor suppressor pathway. In vivo experiments confirmed that IMAT1 silencing could significantly inhibit the growth of subcutaneous tumors and prolong the survival period of tumor-bearing mice. Our findings demonstrated that the high expression of IMAT1 is the inherent reason for the loss of the tumor suppressive properties of KLF4 during meningioma progression. Therefore, we believe that IMAT1 may be a potential biological marker and treatment target for meningiomas.

A novel human KRAB-related zinc finger gene ZNF425 inhibits mitogen-activated protein kinase signaling pathway

( Yue Qun Wang ),( Xiang Li Ye ),( Jun Mei Zhou ),( Yong Qi Wan ),( Hua Ping Xie ),( Yun Deng ),( Yan Yan ),( Yong Qing Li ),( Xiong Wei Fan ),( Wu Zhou Yuan ),( Xiao Yang Mo ),( Xiu Shan Wu ) 생화학분자생물학회(구 한국생화학분자생물학회) 2011 BMB Reports Vol.44 No.1

Zinc finger (ZNF) proteins play a critical role in cell growth, proliferation, apoptosis, and intracellular signal transduction. In this paper, we cloned and characterized a novel human KRAB-related zinc finger gene, ZNF425, which encodes a protein of 752 amino acids. ZNF425 is strongly expressed in the three month old human embryos and then is almost undetectable in six month old embryos and in adult tissues. An EGFP-ZNF425 fusion protein can be found in both the nucleus and the cytoplasm. ZNF425 appears to act as a transcription repressor. Over-expression of ZNF425 inhibits the transcriptional activities of SRE, AP-1, and SRF. Deletion analysis indicates that the C2H2 domain is the main region responsible for the repression. Our results suggest that the ZNF425 gene is a new transcriptional inhibitor that functions in the MAPK signaling pathway. [BMB reports 2011; 44(1): 58-63]