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1. chinaXiv:202003.00008 [pdf]

Germline Polymorphisms and Length of Survival of Nasopharyngeal Carcinoma: An Exome-Wide Association Study in Multiple Cohorts

Yun-Miao Guo; Jie-Rong Chen; Yan-Chun Feng; Chua, Melvin L. K. ; Zeng, Yanni ; Edwin Pun Hui; Allen K. C. Chan; Lin-Quan Tang; Lin Wang; Qian Cui; Hui-Qiong Han; Chun-Ling Luo; Guo-Wang Lin; Yan Liang; Yang Liu; Zhong-Lian He; Yu-Xiang Liu; Pan-Pan Wei; Chu-Jun Liu; Wan Peng
Subjects: Medicine, Pharmacy >> Clinical Medicine

Germline polymorphisms have been linked with differential survival outcomes in cancers but have not been well studied in nasopharyngeal carcinoma (NPC). Here, two-phase association study is conducted to discover germline polymorphisms that are associated with the prognosis of NPC. The discovery phase includes two consecutive hospital cohorts of patients with NPC from Southern China. Exome-wide genotypes at 246,173 single nucleotide polymorphisms (SNPs) are determined, followed by survival analysis for each SNP under Cox proportional hazards regression model. Candidate SNP is replicated in another two independent cohorts from Southern China and Singapore. Meta-analysis of all samples (n = 5,553) confirm that the presence of rs1131636-T, located in the 3′-UTR of RPA1, confers an inferior overall survival (HR = 1.33, 95% CI = 1.20-1.47, P = 6.31 × 10-8). Bioinformatics and biological assays show that rs1131636 has regulatory effects on upstream RPA1. Functional studies further demonstrate that RPA1 promoted the growth, invasion, migration, and radioresistance of NPC cells. Additionally, miR-1253 has been identified as a suppressor for RPA1 expression, likely through regulation of its binding affinity to rs1131636 locus. Collectively, these findings provide a promising biomarker aiding in stratifying patients with poor survival, as well as a potential drug target for NPC.

submitted time 2020-03-06 Hits36670Downloads2367 Comment 0

2. chinaXiv:201712.02112 [pdf]

An elevated pretreatment serum globulin level predicts a poor prognosis of nasopharyngeal carcinoma

ZHONG Liting; WANG Hui; LIANG Huanqing; SU Mengru; LIU Chengdong; WU Dehua
Subjects: Medicine, Pharmacy >> Preclinical Medicine

Objective To investigate the value of serum globulin levels before treatment in predicting the prognosis of patients with nasopharyngeal carcinoma (NPC). Methods A total of 127 patients with non-disseminated NPC were recruited between January, 2009 and December, 2013 at Nanfang Hospital. The pretreatment serum globulin levels were analyzed with the receiver-operating characteristic (ROC) curve analysis to select the cut-off point for low and high pretreatment serum globulin levels. Kaplan-Meier and multivariable analyses were used to evaluate the predictive value of serum globulin levels. Results The ROC curve analysis determined 30.05 g/L as the optimal cut-off value for pretreatment serum globulin level, which was significantly associated with gender (P=0.024) and N stage (P=0.016). Kaplan-Meier analysis showed that a high pretreatment serum globulin level (>30.05 g/L) significantly predicted poor progression-free survival (P=0.019), overall survival (P=0.034)and distant metastasis-free survival (P=0.049); multivariate analysis identified pretreatment serum globulin level as an independent prognostic factor for progression-free survival (HR=2.344, P=0.031). Conclusion Pretreatment serum globulin level may serve as a valuable marker to predict the prognosis of patients with NPC.

submitted time 2017-12-27 From cooperative journals:《南方医科大学学报》 Hits948Downloads535 Comment 0

3. chinaXiv:201605.00771 [pdf]

Screening and identification of post-traumatic stress-related serum factors in children with Wilms' tumors

Zhang, Junjie; Guo, Fei; Wang, Lei; Zhao, Wei; Zhang, Da; Yang, Heying; Wang, Jiaxiang; Hu, Qian; Yu, Jiekai; Zheng, Shu; Niu, Lili; Yang, Fuquan;
Subjects: Biology >> Biophysics >> Oncology

Wilms' tumors are one of the most common malignant, solid intra-abdominal tumors observed in children. Although potential tumor markers have been found, inflammatory cytokines interfere with the process of specific protein identification. The present study was undertaken to identify post-traumatic stress-related factors of Wilms' tumors and to verify the accuracy of early-stage tumor-specific serum protein markers. Serum samples were screened for differentially-expressed proteins using surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF-MS). Potential markers were isolated and purified using solid-phase extraction (SPE) and SDS-PAGE. Following enzymatic digestion of the protein samples, the peptide fragments were detected with high performance liquid chromatography-mass spectrometry. The obtained peptide mass fingerprint was searched in the Swiss-Prot protein sequence database via the Mascot search engine. Differentially-expressed proteins were verified using western blot analysis. Differentially-expressed proteins with a mass/charge of 5,816 were screened out using SELDI-TOF-MS, and significant differences between the tumor and control groups, and the trauma and control groups were observed. Target proteins were isolated and purified using SPE and SDS-PAGE. Thioredoxin 1 (Trx1) was found to be differentially expressed. In the serum of children with Wilms' tumors, there was an increase in the level of the post-traumatic stress-related inflammatory factor, Trx1, as compared with the normal control group. Thus, the results of this study indicate that Trx1 presents a potential post-traumatic stress-related factor of Wilms' tumors.

submitted time 2016-05-05 Hits1639Downloads897 Comment 0

4. chinaXiv:201605.00728 [pdf]

Expression of the galectin-9-Tim-3 pathway in glioma tissues is associated with the clinical manifestations of glioma

Liu, Zengjin; He, Xin; Li, Shouwei; Wu, Chenxing; Yu, Chunjiang; Han, Huamin; Wang, Shengdian;
Subjects: Biology >> Biophysics >> Oncology

Glioma is known to induce local and systemic immunosuppression, which inhibits antitumor T cell responses. The galectin-9-Tim-3-pathway negatively regulates T cell pathways in the tumor immunosuppressive environment. The present study assessed the expression of Tim-3 and galectin-9 in glioma patients, and evaluated the association between the expression of Tim-3 and galectin-9 with clinical characteristics. The present study identified that Tim-3 expression was significantly increased in peripheral blood T cells of glioma patients compared with those of healthy controls, and was additionally increased on tumor-infiltrating T cells. The expression of Tim-3 on tumor-infiltrating T cells was associated with the World Health Organization (WHO) grade of glioma, but negatively correlated with the Karnofsky Performance Status score of the glioma patients. Immunohistochemical analysis revealed that the expression of galectin-9 in tumor tissues was associated with Tim-3 expression on tumor-infiltrating T cells and the WHO grade of glioma. These findings suggest that the galectin-9-Tim-3 pathway may be critical in the immunoevasion of glioma and may be a potent target for immunotherapy in glioma patients.

submitted time 2016-05-05 Hits1528Downloads844 Comment 0

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