p63 (Phospho-Ser395) ELISA Kit

Objectives/Hypothesis To establish comprehensive transcriptomic profiles of cholesteatoma perimatrix tissue and granulation tissue from chronic otitis media (COM) that did not develop cholesteatoma, which can indicate molecular pathways involved in the cholesteatoma perimatrix pathology and invasiveness. Study Design Retrospective Case Series. Methods Transcriptome data were obtained from cholesteatoma perimatrix tissue and COM granulation tissue by an Illumina iScan microarray. Differentially expressed genes (DEGs) were subsequently analyzed using both bioinformatical functional annotation and network analysis. Expression of candidate genes (MMP9 and LCN2) was validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) on a larger group of samples. Results Analysis of the transcriptome led to the identification of 169 differentially expressed genes between investigated tissues. Bioinformatic analysis suggested that most significant biological processes involving DEGs were previously described in cholesteatoma pathology. Network analysis identified ERBB2, TFAP2A, and TP63 as major hubs of the DEGs molecular network. Furthermore, it was observed that the cellular component most significantly enriched in DEGs was extracellular space containing 47 DEGs. Using qRT-PCR, it was confirmed that mRNA levels of the major extracellular hub (MMP9) are increased, whereas its interacting molecule (LCN2) mRNA levels were decreased in cholesteatoma perimatrix tissue compared to COM granulation tissue. Conclusions The current study approach offers an overall look at molecular mechanisms that describe the cholesteatoma entity by focusing exclusively on the perimatrix processes in comparison to COM granulation tissue. The observed differences in gene expression between cholesteatoma perimatrix and COM granulation tissue could suggest novel markers potentially influenced by the perimatrix-matrix molecular interplay, which is not present in COM without cholesteatoma. Level of Evidence NA Laryngoscope, 130:E220-E227, 2020

Genome-wide association studies (GWASs) have consistently identified chromosome 3q28 as a lung cancer susceptibility region. To further characterize the potential genetic mechanism of the variants in this region, we conducted a fine-mapping study on chromosome 3q28 region. We performed a target resequencing in 200 lung cancer cases and 300 controls in the screening and followed by validation in multi-ethnic lung cancer GWASs with 12,843 cases and 12,639 controls. For our identified novel variants, we conducted expression quantitative trait loci (eQTL) analysis to reveal the potential target genes. Two susceptibility variants were identified (rs4396880: G>A, OR = 0.35, 95% CI: 0.20-0.62, P = 3.01x10(-4); and rs3856776: C>T, OR = 2.05, 95% CI: 1.32-3.18, P = 1.49x10(-3)) and further supported in Asian population (rs4396880: OR = 0.88, P = 7.43x10(-6); and rs3856776: OR = 1.17, P = 1.64x10(-4)). The eQTL analysis showed the A allele of rs4396880 was significantly associated with higher mRNA expression of TP63 (P = 1.70x10(-4)) in lung tissues, while rs3856776 showed significant association with the expression of LEPREL1-AS1 (P = 6.90x10(-3)), which was the antisense RNA of LEPREL1 and could suppress the translation of LEPREL1. Notably, LEPREL1 was aberrantly downregulated (P = 2.54x10(-18)) in lung tumor tissues based on TCGA database. In conclusion, this is the first fine-mapping analysis of 3q28 region in Han Chinese, and we found two variants associated with lung cancer susceptibility in Asian population. What's more, rs3856776 was newly identified and might modulate lung cancer susceptibility by suppressing the function of LEPREL1.