Jun Zeng’s research while affiliated with Shenzhen Second People's Hospital and other places

Background Dysregulation of lipid metabolism has been implicated in the progression of hepatocellular carcinoma (HCC). We therefore investigated the molecular characteristics of lipid-metabolism-related genes for the prognostic prediction of HCC. Methods Multi-dimensional bioinformatics analysis was conducted to comprehensively analyzed the lipid metabolism-related genes (IMRG) and construct the prognostic prediction signature. Results A total of 770 HCC patients and their corresponding 776 IMRGs were downloaded from three databases. The HCC patients were classified into 2 molecular clusters, which were associated with overall survival, clinical characteristics, and immune cells. The biological function of the differentially expressed IMRGs in the 2 clusters showed that the genes were associated with tumor-related metabolism pathways. A 6 IMRGs signature (6-IS), including FMO3, SLC11A1, RNF10, KCNH2, ME1, and ZIC2 were established for HCC prognostic prediction, which was found to be an independent prognostic factor. Performance of the 6-IS prognostic signature was verified in a validation set and compared with an external data set. Results revealed that the 6-IS signature could effectively predict the prognosis of patients with HCC. Conclusion This study provides new insights into the role of IMRG in the pathogenesis of HCC and presents a novel signature 6-IS to predict the prognosis of HCC.

Background Emerging evidence has shown the involvement of dysregulated transfer RNAs (tRNAs) and small RNAs derived from transfer RNAs (tsRNAs) in the pathophysiology of human diseases. The role of tRNAs and tsRNAs in systemic lupus erythematosus (SLE) remains unclear. Therefore, this study aims to investigate the possible regulatory roles of tRNAs and tsRNAs in the pathological mechanism of SLE. Methods Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of 20 SLE patients and 20 normal controls (NCs) to obtain tRNAs and tsRNAs, followed by tRNA and tsRNA expression profiling by the NextSeq system. Target genes were predicted by informatics analysis. Subsequently, to explore the function of messenger RNA (mRNA) in these target genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the Cytoscape plug-in BinGo, the DAVID database, and Cytoscape software. Results A total of 101 tRNAs and 355 tsRNAs were found to be differentially expressed in SLE patients versus NCs by RNA microarray. GO analysis revealed that the altered target genes of the selected tRNAs and tsRNAs were most enriched similarly in immune response and the immune system process. Moreover, KEGG pathway analysis demonstrated that altered target genes of tRNAs were most enriched in systemic lupus erythematosus, while the altered target genes of tsRNAs were most enriched in the T cell receptor signalling pathway, Th1 and Th2 cell differentiation and primary immunodeficiency. These pathways may be related to the initiation of SLE. Conclusion Our results provide a novel perspective for studying the tRNA-related and tsRNA-related pathogenesis of SLE.

Background Retinitis pigmentosa (RP) is one of the major types of hereditary retinal dystrophies with extreme genotypic heterogeneity. To date, more than 80 genes have been identified to be associated with RP in human. Method Here, we presented a clinical genetic study of three Chinese man manifested with night vision blindness and complete loss of midperipheral visual field. All of these three probands have been identified with loss of both central vision and far peripheral visual field. Gradual loss of rod cells followed by subsequent loss of cone cells have been identified in these probands. Targeted next generation sequencing and Sanger sequencing have been performed to understand the pathogenic variants underlying the disease phenotype in these three unrelated Chinese probands. Results Targeted next generation sequencing and Sanger sequencing identified three homozygous novel mutations (c.1880C>A; c.1459_1460delGA, and c.392G>A) in the MERTK gene in these three unrelated Chinese proband. In the first proband, the identified mutation (c.1880C>A) leads to the formation of a premature stop codon followed by the formation of a truncated mer‐tyrosine kinase (MERTK) protein (p.Ser627*) product which predicted to be disease causing. In the second proband, the identified deletion (c.1459_1460delGA) leads to the formation of a frameshift which also finally results in the formation of a truncated MERTK protein (p.Asp487Leufs*57) product which also predicted to be disease causing. In the third proband, the identified mutation (c.392G>A) leads to the formation of a premature stop codon followed by the formation of a truncated MERTK protein (p.Trp131*) product which also predicted to be disease causing. Hence, these three mutations are loss‐of‐function mutations. These three mutations were absent in unaffected family members and in 100 normal healthy controls. Conclusion Our present study also demonstrates the significance of targeted next generation sequencing in determining the genetic basis of RP.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Complementarity-determining region 3 (CDR3) of B-cell receptors (BCRs) and T-cell receptors are the major site of antigen recognition, which determines a unique clone type, and are considered to be the representative of the disease. In the present study, high-throughput sequencing was used to analyze the association of characteristics of the BCR immunoglobulin heavy chain (IGH) and the T-cell receptor β chain (TRB) CDR3 genes in PTC and corresponding pericarcinous tissues from patients. A difference of CDR3 length distributions of total IGH CDR3 sequences between the two groups was revealed. IGHV3-11/IGHJ6, TRBV2/TRBJ1-2 and TRBV2/TRBJ1-1 may be biomarkers for the development of PTC. Furthermore, it was revealed that the extent of the common clonotype expressions at the amino acid level was slightly higher compared with the nucleotide level. The Shannon entropy demonstrated a diversity reduction in PTC compared with the pericarcinous group, and the highly expended clone (HEC) expression of PTC was higher compared with that of the corresponding pericarcinous group. Additionally, the highest clone frequency percentage of IGH and TRB was at 0.1-1.0% degree of expansion, as HEC expression was higher in PTC compared with the matched group. There was no shared clone of HECs in the two groups either at the amino acid level or at the nucleotide expression level. The differential expression of CDR3 sequences of PTC have been identified in the present study. Further research is required for assessing the immune repertoire size, diversity, cloning tracking and finding public clones of T-cell and B-cell populations in the development of PTC.