Integrated Analyses of Gene Expression Profiles Digs out Common Markers for Rheumatic Diseases

Objective

Rheumatic diseases have some common symptoms. Extensive gene expression studies, accumulated thus far, have successfully identified signature molecules for each rheumatic disease, individually. However, whether there exist shared factors across rheumatic diseases has yet to be tested.

Methods

We collected and utilized 6 public microarray datasets covering 4 types of representative rheumatic diseases including rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and osteoarthritis. Then we detected overlaps of differentially expressed genes across datasets and performed a meta-analysis aiming at identifying common differentially expressed genes that discriminate between pathological cases and normal controls. To further gain insights into the functions of the identified common differentially expressed genes, we conducted gene ontology enrichment analysis and protein-protein interaction analysis.

Results

We identified a total of eight differentially expressed genes (TNFSF10, CX3CR1, LY96, TLR5, TXN, TIA1, PRKCH, PRF1), each associated with at least 3 of the 4 studied rheumatic diseases. Meta-analysis warranted the significance of the eight genes and highlighted the general significance of four genes (CX3CR1, LY96, TLR5, and PRF1). Protein-protein interaction and gene ontology enrichment analyses indicated that the eight genes interact with each other to exert functions related to immune response and immune regulation.

Conclusion

The findings support that there exist common factors underlying rheumatic diseases. For rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and osteoarthritis diseases, those common factors include TNFSF10, CX3CR1, LY96, TLR5, TXN, TIA1, PRKCH, and PRF1. In-depth studies on these common factors may provide keys to understanding the pathogenesis and developing intervention strategies for rheumatic diseases.     

A Genome-Wide mRNA Expression Profile in Caenorhabditis elegans under Prolonged Exposure to 1750MHz Radiofrequency Fields

Objective

C. elegans has been used as a biomonitor for microwave-induced stress. However, the RF (radiofrequency) fields that have been used in previous studies were weak (≤1.8W/kg), and the bio-effects on C. elegans were mostly negative or ambiguous. Therefore, this study used more intense RF fields (SAR = 3W/kg) and longer time course of exposure (60h at 25°C, L1 stage through adult stage) to investigate the biological consequences of 1750 MHz RF fields in wild-type worms.

Methods

The growth rates and lifespans of RF-exposure group and the control group were carefully recorded. RNA samples were collected at L4 (35h) and gravid adult (50h) stages for further high-throughput sequencing, focusing on differences between the RF-exposure and the sham control groups.

Results

The RF-exposed and sham control groups developed at almost the same rate and had similar longevity curves. In L4 stage worms, 94 up-regulated and 17 down-regulated genes were identified, while 186 up-regulated and 3 down-regulated genes were identified in adult stage worms. GO analysis showed that the differentially expressed genes at 35h were associated with growth, body morphogenesis and collagen and cuticle-based development. Genes that were linked to growth rate and reproductive development were differentially expressed at 50h. Some embryonic and larval development genes in the offspring were also differentially expressed at 50h. Ten genes were differentially expressed at both 35h and 50h, most of which were involved in both embryonic and larval developmental processes. Although prolonged RF fields did not induce significant temperature increase in RF exposure groups, the temperature inside worms during exposure was unknown.

Conclusions

No harmful effects were observed in prolonged exposure to 1750 MHz RF fields at SAR of 3W/kg on development and longevity of C. elegans. Although some differentially expressed genes were found after prolonged RF exposure, these differences were ascribed to oscillating gene expression patterns in L4 and gravid adult worms. It was also difficult to rule out a weak thermal effect caused by prolonged RF exposure inside the worms.