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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 Hits36669Downloads2366 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:201605.00729 [pdf]

Identification of Liver Epithelial Cell-derived Ig Expression in mu chain-deficient mice

Shao, Wenwei; Zhang, Chi; Ma, Junfan; Zhu, Zhu; Gong, Xiaoting; Qiu, Xiaoyan; Liu, Enyang; Zhang, Long; Qiu, Xiaoyan; Qin, Zhihai;
Subjects: Biology >> Biophysics

Growing evidence indicates that B cells are not the only source of immunoglobulin (Ig). To investigate this discovery further, we used mu MT mice, which have a disruption of the first transmembrane exon of the mu heavy chain and do not express the membrane form of IgM. These mice lack mature B cells and thus serve as a good model to explore Ig expression by liver epithelial cells. We found that Ig heavy chains (mu, delta, gamma and alpha) and light chains (kappa and lambda) were expressed in sorted liver epithelial cells of mu MT mice. Surprisingly, each heavy chain class showed its respective variable region sequence characteristics in their variable region, instead of sharing the same VDJ usage, which suggests that class switching does not occur in liver epithelial cells. Moreover, the gamma and alpha chains, but not the mu and delta chains, showed mutations in the variable region, thus indicating that different classes of Ig have different activities. Our findings support the concept that non-B cells, liver epithelial cells here, can produce different classes of Ig.

submitted time 2016-05-05 Hits1184Downloads630 Comment 0

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