Identification of potential prognosticators for sepsis through expression analysis of transcriptomic data from sepsis survivors and nonsurvivors

Background@#Infection can be severely complicated by a dysregulated, whole-body inflammatory response known as sepsis. While previous research showed that genetic predisposition is linked to outcome differences, current patient characterization fails to determine which septic patients have greater tendencies to develop into severe sepsis or go into septic shock. As such, the identification of prognostic biomarkers may assist in identifying these high-risk patients and help improve the clinical management of the disease.@*Objective@#In this study, we aimed to identify molecular patterns involved in sepsis. We also aimed to identify essential genes associated with the disease’s survival which could serve as potential prognosticators for the disease. @*Methods@#We used weighted gene co-expression analysis (WGCNA) to analyze GSE63042, an RNA expression dataset from 129 patients with systemic inflammatory response syndrome or sepsis, including 78 sepsis survivors and 28 sepsis nonsurvivors. This analysis included identifying gene modules that differentiate sepsis survivors from nonsurvivors and qualitatively assessing differentially expressed genes. We then used STRING’s protein-protein interaction and gene ontology analysis to determine the functional and pathway relationships of the genes in the top modules. Lastly, we assessed the prognosticator abilities of the hub genes using ROC analysis. @*Results@#We found four diverse co-expression gene modules significantly associated with sepsis survival. Our differential gene expression analysis, combined with protein-protein interaction and gene ontology analysis, revealed that the hub genes of these modules – TAF10, SNAPIN, PSME2, PSMB9, JUNB, and CEBPD – may serve as candidate markers for sepsis prognosis. These markers were significantly downregulated in sepsis nonsurvivors compared with sepsis survivors.@*Conclusion@#Weighted gene co-expression analysis, gene ontology enrichment analysis, and proteinprotein network interaction analysis of transcriptomic data from sepsis survivors and nonsurvivors revealed TAF10, SNAPIN, PSME2, PSMB9, JUNB, and CEBPD as potential biomarkers for sepsis prognosis. These genes are associated with functions related to proper immune response, and their downregulation in sepsis nonsurvivors suggests eventual immune exhaustion in late sepsis. Further analyses, however, are necessary to validate their roles in sepsis progression and patient survival.

The Expression of c-Jun and JunB in Various Skin Tumors / 대한피부과학회지

BACKGROUND: c-Jun along with JunB, JunD, and the Fos group proteins comprise the core members of the activator protein 1 (AP1) family of transcription factors. Recently, many studies have demonstrated the key roles of AP1 in regulating a wide spectrum of biological processes, including tumorigenesis. We therefore hypothesized that c-Jun and JunB influence the differentiation and malignant change of various skin tumors. OBJECTIVE: We measured the expression levels of c-Jun and JunB in different skin tumors. METHODS: The expressions of c-Jun and JunB were examined by performing the immunohistochemical staining of 55 specimens of skin tumors, including 13 cases of seborrheic keratosis, 4 cases of keratoacanthoma, 9 cases of actinic keratosis, 4 cases of Bowen's disease, 4 cases of basal cell carcinoma, 16 cases of squamous cell carcinoma, and 5 cases of malignant melanoma. RESULTS: Immunohistochemical analysis of the skin tumor tissue samples revealed a significantly higher expression of c-Jun in malignant skin tumors (basal cell carcinoma, squamous cell carcinoma, malignant melanoma) than in benign (seborrheic keratosis, keratoacanthoma) or premalignant skin tumors (actinic keratosis, Bowen's disease). The expression of JunB, however, was significantly lower in malignant skin tumors than in benign skin tumors. CONCLUSION: These findings showed that c-Jun has a positive association with skin malignancies, while JunB has a negative association with skin malignancies. The role of AP1 as key regulators of cell proliferation and epidermal tumor progression is suggested.

Construction of eukaryotic expression vector of wtp53/junB fusion gene / 西安交通大学学报(医学版)

Objective To construct wtp53/junB fusion gene and its eukaryotic expression vector in order to provide the basis for further application of polygene union therapy in hepatocellular carcinoma. Methods Polymerase chain reaction (PCR), reverse transcription-PCR (RT-PCR) and gene recombination techniques were used to construct the eukaryotic vector of pEGFP-C1-wtp53/junB fusion gene, which carries the enhanced green fluorescent protein (EGFP). The transfection of pEGFP-C1-wtp53/junB in hepatoma HepG2 cells was detected by the location of green fluorescence. Results The DNA sequence of wtp53/junB fusion gene was successfully cloned into the pEGFP-C1 plasmid and the sequence was the same as what we expected. Green fluorescence located on cell nucleus proved that pEGFP-C1-wtp53/junB was transfected into HepG2 cell line successfully. Conclusion We successfully constructed the eukaryotic vector of pEGFP-C1-wtp53/junB fusion gene, which carries the EGFP, and transfects it into human hepatoma cell nucleus. It may lay the basis for studying the synergetic effect of wtp53 and junB in hepatocellular carcinoma.

Comparison of the Expression Profile of JunB, c-Jun, and S100A8 (Calgranulin A) in Psoriasis Vulgaris and Guttate Psoriasis

BACKGROUND: Psoriasis is a chronic, inflammatory, immune- mediated skin disease. Recently, several psoriasis-linked genetic loci have been reported; PSORS4 contains S100A8 (calgranulin A), and PSOR6 (19p13) locus harbors JunB (19p13.2). S100A8 is considered to be a marker of inflammation in a variety of diseases. The expression of JunB and c-Jun have been reported to be reduced in psoriatic lesions. OBJECTIVE: We attempted to assess the role and correlation of S100A8, JunB, and c-Jun in the pathogenesis of guttate psoriasis and psoriasis vulgaris by studying whether any difference of immunohistochemical expression existed. METHODS: Skin biopsy specimens from patients with psoriasis vulgaris (n=37) and guttate psoriasis (n=17), and a normal skin controls (n=9) were utilized in the study. Formalin-fixed and paraffin-embedded tissue sections were prepared and JunB, c-Jun, and calgranulin A were immunohistochemically stained in order to compare the expression of those three proteins in each group. RESULTS: Reduced JunB expression was observed in patients with psoriasis vulgaris and guttate psoriasis, as compared to patients in the control group; however, c-Jun expression was reduced only in the psoriasis vulgaris group. The expression of S100A8 increased in the psoriasis groups as compared to the control group. In addition, the expression of S100A8 was different between the psoriasis vulgaris and guttate psoriasis groups; S100A8 was expressed more profoundly in the guttate psoriasis group (p<0.05). CONCLUSION: Our results indicate that S100A8 contributes to the pathogenesis of guttate psoriasis, and it may be a good target for therapy for guttate psoriasis provoked by microorganisms.

Methylation status of the SOCS 1 and JUNB genes in chronic myeloid leukemia patients / Padrão de metilação dos genes SOCS 1 e JUNB em pacientes com leucemia mieloide crônica

Alterations in the methylation status of genes may contribute to the progression of Chronic Myeloid Leukemia (CML). In this study, the methylation status in exon2 of SOCS- 1 and promoter regions of both SOCS- 1 and JUNB were evaluated in CML patients. The methylation status of these genes was analyzed using methylation- specific Polymerase Chain Reaction (MSP) in 30 samples from CML patients, 30 samples from these same patients after hematopoietic stem cell transplantation (HSCT) and 30 samples from healthy controls. The samples of CML patients presented methylation as follows: JUNB gene (3.3 percent), promoter region of the SOCS- 1 gene (6.6 percent) and exon2 of the SOCS- 1 gene (46.6 percent). The samples of the healthy individuals presented methylation (10 percent, P = 0.002) only in exon 2 of the SOCS- 1 gene. After transplantation, patients presented alterations in the methylation status of the promoter region of the SOCS- 1 gene (6.6 percent), exon2 of SOCS- 1 (46.6 percent) and the promoter region of the JUNB gene (16.6 percent). Methylation of the promoter regions of the SOCS- 1 gene and the JUNB gene is not a frequent event in CML. In contrast, SOCS- 1 gene methylation in exon2 is a frequent event, susceptible to alterations in status after HSCT with possible implications for the progression of this disease.

Alteração no padrão de metilação gênica pode contribuir para a progressão da leucemia mielóide crônica (LMC). Neste estudo, o padrão de metilação no exon 2 do gene SOCS- 1 e região promotora de ambos SOCS- 1 e JUNB foram avaliadas em pacientes com LMC. O padrão de metilação desses genes foi analisado usando a técnica " methylation- specific polymerase chain reaction (MSP)" em 30 amostras de pacientes com LMC, 30 amostras desses mesmos pacientes após transplante de medula óssea (TMO) e 30 amostras controle de indivíduos saudáveis. As amostras de pacientes com LMC apresentaram o seguinte padrão de metilação: gene JUNB (3.3 por cento), região promotora do gene SOCS- 1 (6.6 por cento) e exon2 do gene SOCS- 1 (46.6 por cento). Amostras dos indivíduos saudáveis apresentaram metilação somente no exon 2 do gene SOCS- 1 (10 por cento, P = 0.002). Após o transplante, os pacientes apresentaram alterações no padrão de metilação da região promotora do gene SOCS- 1 (6.6 por cento), no exon2 do gene SOCS- 1 (46.6 por cento) e na região promotora do gene JUNB (16.6 por cento). Metilação das regiões promotoras dos genes SOCS- 1 e JUNB não é um evento frequente em LMC. Em contraste, metilação no exon 2 do gene SOCS- 1 apresenta- se como um evento frequente, suscetível a alterações no padrão de metilação após TMO.

Expression of AP-1 subunits in skin tumor and its significance / 中国癌症杂志

Purpose:AP-1(activator protein-1) is closely associated with cell differentiation,proliferation,apoptosis and tumorigenesis.We investigated the expression of AP-1 subunits in skin tumor and its adjacent skin tissue and their roles in the occurrence and development of skin tumor.Methods:ABC immunohistochemistry was applied to detect c-jun,p-c-jun,JunB,JunD,c-fos,Fra-1,and Fra-2 expression in skin basal cell carcinoma,squamous cell carcinoma,Bowens disease and keratacanthoma.Results:The expression of c-jun and p-c-jun were increased dramatically in basal cell carcinoma,squamous cell carcinoma,Bowens disease and keratacanthoma and JunB was decreased sharply in basal cell carcinoma.Conclusions:c-jun is a positive regulator of cell proliferation and tumorigenesis in skin.JunB has an antagonistic function for c-jun.