Person: Wang, Jiping
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Wang
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Jiping
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Wang, Jiping
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Publication MiR-650 represses high-risk non-metastatic colorectal cancer progression via inhibition of AKT2/GSK3β/E-cadherin pathway(Impact Journals LLC, 2017) Zhou, Chunxian; Cui, Fengyun; Li, Jiali; Wang, Diyi; Wei, Yingze; Wu, Ying; Wang, Jiping; Zhu, Hongguang; Wang, ShuyangAlthough 5-year survival rate of non-metastatic colorectal cancer (CRC) is high, about 10% of patients in stage I and II still develop into metastatic CRC and eventually die after resection. Currently, there is no effective biomarker for predicting the prognosis of non-metastatic CRC in clinical practice. In this study, we identified miR-650 as a biomarker for prognosis prediction. We observed that the expression of miR-650 in tumor tissues had a positive association with overall survival. MiR-650 inhibited cell growth and invasion in vitro and in vivo. Furthermore, miR-650 targeted AKT2 and repressed the activation of the AKT pathway (AKT2/GSK3β/E-cadherin). Thus it induced the translocation of E-cadherin and β-catenin in cancer cells. Our results highlight the potential of miR-650 as a prognostic prediction biomarker and therapeutic target in non-metastatic CRC via inhibition of the AKT2/GSK3β/E-cadherin pathway.Publication Comparison of a Lymph Node Ratio–Based Staging System With the 7th AJCC System for Gastric Cancer(Ovid Technologies (Wolters Kluwer Health), 2012) Wang, Jiping; Dang, Ping; Raut, Chandrajit; Pandalai, Prakash K.; Maduekwe, Ugwuji N.; Rattner, David; Lauwers, Gregory Y.; Yoon, SamOBJECTIVES: The American Joint Committee on Cancer (AJCC) staging system for gastric cancer bases N status on absolute number of metastatic nodes, regardless of the number of examined nodes. We examined a modified staging system utilizing node ratio (Nr), the ratio of metastatic to examined nodes. METHODS: A total of 18,043 gastric cancer patients who underwent gastrectomy were identified from the US Surveillance, Epidemiology, and End Results (SEER) database. A training set was divided into 5 Nr groups, and a TNrM staging system was constructed. Median survival and overall survival, based on 7th edition AJCC and TNrM staging systems, were compared, and the analysis was repeated in a validation set. RESULTS: Median examined nodes were 10 to 11. For the training set, overall survival for all 5 AJCC N categories was significantly different when subgrouped into 15 or fewer versus more than 15 examined nodes, but overall survival was similar regardless of the number of examined nodes in 4 of 5 Nr categories. Seven AJCC stages had statistically different overall survival between subgroups, whereas only 1 TNrM stage had statistically different overall survival between subgroups. When misclassification was defined as any subgroup in which median survival fell outside the 95% confidence interval of the group's overall median survival, AJCC staging misclassified 57% of patients and TNrM staging misclassified only 12%. Similar results were found in the validation set. CONCLUSIONS: The AJCC system classifies SEER gastric cancer patients into stages in which subgroups often have wide variations in survival. For patients undergoing limited lymph node analysis, the proposed TNrM system may predict survival more accurately.Publication Germline variants and advanced colorectal adenomas: Adenoma Prevention with Celecoxib trial genome-wide association study(American Association for Cancer Research (AACR), 2013) Wang, Jiping; Carvajal-Carmona, Luis G.; Chu, Jen-Hwa; Zauber, Ann G.; KUBO, Michikai; Matsuda, Koichi; Dunlop, Malcolm; Houlston, Richard S.; Sieber, Oliver; Lipton, Lara; Gibbs, Peter; Martin, Nicholas G.; Montgomery, George Glennon; Young, Joanne; Baird, Paul N.; Ratain, Mark J.; Nakamura, Yusuke; Weiss, Scott; Tomlinson, Ian; Bertagnolli, MonicaPurpose: Identification of single nucleotide polymorphisms (SNPs) associated with development of advanced colorectal adenomas. Experimental Design: Discovery Phase: 1,406 Caucasian patients (139 advanced adenoma cases and 1,267 controls) from the Adenoma Prevention with Celecoxib (APC) trial were included in a genome-wide association study (GWAS) to identify variants associated with post-polypectomy disease recurrence. Genome-wide significance was defined as false discovery rate < 0.05, unadjusted p=7.4×10−7. Validation Phase: Results were further evaluated using 4,175 familial colorectal adenoma or CRC cases and 5,036 controls from patients of European ancestry (COloRectal Gene Identification consortium, Scotland, Australia and VQ58). Results: Our study identified eight SNPs associated with advanced adenoma risk in the APC trial (rs2837156, rs7278863, rs2837237, rs2837241, rs2837254, rs741864 at 21q22.2, and rs1381392 and rs17651822 at 3p24.1, at p<10–7 level with odds ratio – OR>2). Five variants in strong pairwise linkage disequilbrium (rs7278863, rs2837237, rs741864, rs741864 and rs2837241, r2=0.8–1) are in or near the coding region for the tight junction adhesion protein, IGSF5. An additional variant associated with advanced adenomas, rs1535989 (minor allele frequency 0.11; OR 2.09; 95% confidence interval 1.50–2.91), also predicted CRC development in a validation analysis (p=0.019) using a series of adenoma cases or CRC (CORGI study) and 3 sets of CRC cases and controls (Scotland, VQ58 and Australia, N=9,211). Conclusions: Our results suggest that common polymorphisms contribute to the risk of developing advanced adenomas and might also contribute to the risk of developing CRC. The variant at rs1535989 may identify patients whose risk for neoplasia warrants increased colonoscopic surveillance.Publication Inferring the progression of multifocal liver cancer from spatial and temporal genomic heterogeneity(Impact Journals LLC, 2016) Shi, Jie-Yi; Xing, Qingfeng; Duan, Meng; Wang, Zhi-Chao; Yang, Liu-Xiao; Zhao, Ying-Jun; Wang, Xiao-Ying; Liu, Yun; Deng, Minghua; Ding, Zhen-Bin; Ke, Ai-Wu; Zhou, Jian; Fan, Jia; Cao, Ya; Wang, Jiping; Xi, Ruibin; Gao, QiangMultifocal tumors developed either as independent tumors or as intrahepatic metastases, are very common in primary liver cancer. However, their molecular pathogenesis remains elusive. Herein, a patient with synchronous two hepatocellular carcinoma (HCC, designated as HCC-A and HCC-B) and one intrahepatic cholangiocarcinoma (ICC), as well as two postoperative recurrent tumors, was enrolled. Multiregional whole-exome sequencing was applied to these tumors to delineate the clonality and heterogeneity. The three primary tumors showed almost no overlaps in mutations and copy number variations. Within each tumor, multiregional sequencing data showed varied intratumoral heterogeneity (21.6% in HCC-A, 20.4% in HCC-B, 53.2% in ICC). The mutational profile of two recurrent tumors showed obvious similarity with HCC-A (86.7% and 86.6% respectively), rather than others, indicating that they originated from HCC-A. The evolutionary history of the two recurrent tumors indicated that intrahepatic micro-metastasis could be an early event during HCC progression. Notably, FAT4 was the only gene mutated in two primary HCCs and the recurrences. Mutation prevalence screen and functional experiments showed that FAT4, harboring somatic coding mutations in 26.7% of HCC, could potently inhibit growth and invasion of HCC cells. In HCC patients, both FAT4 expression and FAT4 mutational status significantly correlated with patient prognosis. Together, our findings suggest that spatial and temporal dissection of genomic alterations during the progression of multifocal liver cancer may help to elucidate the basis for its dismal prognosis. FAT4 acts as a putative tumor suppressor that is frequently inactivated in human HCC.Publication Thermal Stability of the Human Immunodeficiency Virus Type 1 (HIV-1) Receptors, CD4 and CXCR4, Reconstituted in Proteoliposomes(Public Library of Science, 2010) Zhukovsky, Mikhail A.; Basmaciogullari, Stéphane; Schwartz, Olivier; Pacheco, Beatriz; Wang, Jiping; Madani, Navid; Haim, Hillel; Sodroski, JosephBackground: The entry of human immunodeficiency virus (HIV-1) into host cells involves the interaction of the viral exterior envelope glycoprotein, gp120, and receptors on the target cell. The HIV-1 receptors are CD4 and one of two chemokine receptors, CCR5 or CXCR4. Methodology/Principal Findings: We created proteoliposomes that contain CD4, the primary HIV-1 receptor, and one of the coreceptors, CXCR4. Antibodies against CD4 and CXCR4 specifically bound the proteoliposomes. CXCL12, the natural ligand for CXCR4, and the small-molecule CXCR4 antagonist, AMD3100, bound the proteoliposomes with affinities close to those associated with the binding of these molecules to cells expressing CXCR4 and CD4. The HIV-1 gp120 exterior envelope glycoprotein bound tightly to proteoliposomes expressing only CD4 and, in the presence of soluble CD4, bound weakly to proteoliposomes expressing only CXCR4. The thermal stability of CD4 and CXCR4 inserted into liposomes was examined. Thermal denaturation of CXCR4 followed second-order kinetics, with an activation energy (E\(_a\)) of 269 kJ/mol (64.3 kcal/mol) and an inactivation temperature (T\(_i\)) of 56°C. Thermal inactivation of CD4 exhibited a reaction order of 1.3, an E\(_a\) of 278 kJ/mol (66.5 kcal/mol), and a T\(_i\) of 52.2°C. The second-order denaturation kinetics of CXCR4 is unusual among G protein-coupled receptors, and may result from dimeric interactions between CXCR4 molecules. Conclusions/Significance: Our studies with proteoliposomes containing the native HIV-1 receptors allowed an examination of the binding of biologically important ligands and revealed the higher-order denaturation kinetics of these receptors. CD4/CXCR4-proteoliposomes may be useful for the study of virus-target cell interactions and for the identification of inhibitors.