Transforming Gene Research Articles

Composting swine carcasses with nitrogen transformation microbial strains: Succession of microbial community and nitrogen functional genes

In this study, nitrogen transformation strains, including three ammonium transformation strains, one nitrite strain and one nitrogen fixer, were inoculated at different swine carcass composting stages to regulate the nitrogen transformation and control the nitrogen loss. The final total nitrogen content was significantly increased (p < 0.01). The bacterial communities were assessed by amplicon sequencing and association analysis. Proteobacteria, Actinobacteria, Bacteroidetes and Firmicutes were the four most dominant phyla.,Brevibacterium, Streptomyces and Ochrobactrum had a significant (p < 0.05) and positive correlation with total nitrogen and ammonium nitrogen content in both groups. The quantitative results of nitrogen transformation genes showed that ammonification, nitrification, denitrification and nitrogen fixation were simultaneously present in the composting process of swine carcasses, with the latter two accounting for a higher proportion. The ammonium transformation strains significantly (p < 0.05) strengthened nitrogen fixation and remarkably (p < 0.01) weakened nitrification and denitrification, which, however, were notably (p < 0.05) enhanced by the nitrite strain and nitrogen fixer. In this research, the inoculated strains changed the bacterial structure by regulating the abundance and activity of the highly connected taxa, which facilitated the growth of nitrogen transformation bacteria and regulated the balance/symbiosis of nitrogen transformation processes to accelerate the accumulation of nitrogen.

Hypermethylation of the PTTG1IP promoter leads to low expression in early-stage non-small cell lung cancer.

Despite the clinical requirement for early diagnosis, the early events in lung cancer and their mechanisms are not fully understood. Pituitary tumor transforming gene 1 binding factor (PTTG1IP) is a tumor-associated gene; however, to the best of our knowledge, its association with lung cancer has not been reported. The present study analyzed PTTG1IP expression in early-stage non-small cell lung cancer (NSCLC) samples and investigated its epigenetic regulatory mechanisms. The results revealed that the mRNA level of PTTG1IP in NSCLC tissues was significantly downregulated by 43% compared with that in adjacent tissues. In addition, overexpression of this gene significantly inhibited cell proliferation. According to data from The Cancer Genome Atlas, a significant negative correlation was identified between the PTTG1IP gene methylation level and expression level in lung adenocarcinoma and lung squamous cell carcinoma cases. Reduced representation bisulfite sequencing (RRBS) analysis of six paired early-stage NSCLC tissue samples indicated that the CpG island shore of the PTTG1IP promoter is hypermethylated in lung cancer tissues, which was further validated in 12 paired early-stage NSCLC samples via bisulfite amplicon sequencing. Following treatment with 5-aza-2′-deoxycytidine to reduce DNA methylation in the promoter region, the PTTG1IP mRNA level increased, indicating that the PTTG1IP promoter DNA methylation level negatively regulates PTTG1IP transcription. In conclusion, in early-stage NSCLC, the PTTG1IP gene is regulated by DNA methylation in its promoter region, which may participate in the development and progression of lung cancer.

Development of a shuttle plasmid without host restriction sites for efficient transformation and heterologous gene expression in Clostridium cellulovorans.

Clostridium cellulovorans capable of producing large amounts of acetate and butyrate from cellulose is a promising candidate for biofuels and biochemicals production from lignocellulosic biomass. However, the restriction modification (RM) systems of C. cellulovorans hindered the application of existing shuttle plasmids for metabolic engineering of this organism. To overcome the hurdle of plasmid digestion by host, a new shuttle plasmid (pYL001) was developed to remove all restriction sites of two major RM systems of C. cellulovorans, Cce743I and Cce743II. The pYL001 plasmid remained intact after challenge by C. cellulovorans cell extract. Post-electroporation treatments and culturing conditions were also modified to improve cell growth and colony formation on agar plates. With the improvements, the pYL001 plasmid, without in vivo methylation, was readily transformed into C. cellulovorans with colonies of recombinant cells formed on agar plates within 24h. Three pYL001-derived recombinant plasmids free of Cce743I/Cce743II restriction sites, after synonymous mutation of the heterologous genes, were constructed and transformed into C. cellulovorans. Functional expression of these genes was confirmed with butanol and ethanol production from glucose in batch fermentations by the transformants. The pYL001 plasmid and improved transformation method can facilitate further metabolic engineering of C. cellulovorans for cellulosic butanol production.

Downregulation of G Protein-Coupled Estrogen Receptor (GPER) is Associated with Reduced Prognosis in Patients with Gastric Cancer.

BackgroundThis study is aimed to investigate the prognostic significance of the expression of G protein-coupled estrogen receptor (GPER) in gastric cancer tissue using bioinformatics data and immunohistochemistry.Material/MethodsExpression of GPER mRNA in gastric cancer tissues and normal adjacent tissues was investigated using data from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and Oncomine database. Kaplan-Meier Plotter identified the association between GPER mRNA and prognosis. Correlation between GPER mRNA and DNA methylation used the cBioPortal for Cancer Genomics and the MethHC website. Genes co-expressed with GPER were identified from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) underwent FunRich analysis. Immunohistochemistry and Western blot evaluated GPER protein expression in tissue microarrays (TMAs) and gastric cancer cell lines.ResultsGPER mRNA and protein levels were significantly lower in gastric cancer tissue and cells lined when compared with normal tissues and cells. The results from GSE15459 showed that patients with low levels of GPER mRNA had a reduced overall survival (OS) (P=0.013) and disease-free survival (DFS) (P=0.019). A negative correlation (r=−0.611) between GPER mRNA and DNA methylation was found using the cBioPortal and MethHC. Co-expressed epithelial-mesenchymal transformation (EMT) genes were enriched with GPER (P<0.0001). Cox regression analysis showed that GPER protein expression was an independent prognostic factor (P=0.035)ConclusionsDownregulation of GPER predicts poor prognosis in gastric cancer. GPER may act as a tumor suppressor through the regulation of EMT in gastric cancer.

Identification of the potential therapeutic target gene UBE2C in human hepatocellular carcinoma: An investigation based on GEO and TCGA databases.

Hepatocellular carcinoma (HCC) ranks the third major cause of cancer-associated mortality globally. Numerous studies have attempted to elucidate the underlying mechanisms of HCC using various biomarkers. In the present study, two expression profiles datasets from Gene Expression Omnibus (GSE76427 and GSE84402) and data associated with liver cancer samples from The Cancer Genome Atlas (TCGA) were downloaded for integrated analysis. Five differentially expressed genes (DEGs) exhibiting high expression, including ubiquitin-conjugating enzyme 2C (UBE2C), topoisomerase II α, pituitary tumor transforming gene 1, glypican-3 and polycomb-repressive complex 1, were selected and considered as candidate genes. Enrichment analysis demonstrated that these genes were associated with Gene Ontology terms of cellular components and molecular functions, including regulation of apoptosis, stabilization of p53 and Anaphase Promoting Complex/Cyclosome (APC/C) (APC/C:Cdc20)-mediated degradation of Securin. The expression profiles of these genes in HCC, other human malignancies and different human HCC cell lines were validated using GSE14520, GSE3500 and TCGA data. The results confirmed the upregulation of UBE2C in tissues from patients with HCC or other human malignancies and human liver cancer cell lines, compared with the expression levels in the corresponding adjacent non-tumor tissues and cell lines, respectively. Patients with HCC who exhibited an increased messenger RNA level of UBE2C exhibited a significantly shorter survival time. The results of the present study suggest that the overexpression of UBE2C may be used as a novel prognostic biomarker of HCC.

Two of the three Transformer-2 genes are required for ovarian development in Aedes albopictus

In Drosophila melanogaster, transformer-2 (tra2) plays an essential role in the sex-specific splicing of doublesex (dsx) and fruitless (fru), two key transcription factor genes that program sexual differentiation and regulate sexual behavior. In the present study, the sequences and expression profiles of three tra2 (Aalbtra2) genes in the Asian tiger mosquito, Aedes albopictus (Ae. albopictus) were characterized. Phylogenetic analysis revealed that these paralogs resulted from two duplication events. The first occurred in the common ancestor of Culicidae, giving rise to the tra2-α and tra2-β clades that are found across divergent mosquito genera, including Aedes, Culex, and Anopheles. The second occurred within the tra2-α clade, giving rise to tra2-γ in Ae. albopictus. In addition to the conserved RNA recognition motif (RRM), arginine-rich/serine-rich regions (RS domains) and a linker region, a glycine-rich region located between the RRM and RS2 was observed in Tra2-α and Tra2-γ of Ae. albopictus that has not yet been described in the Tra2 proteins of dipteran insects. Quantitative real-time PCR detected relatively high levels of transcripts from all three tra2 paralogs in 0–2 h embryos, suggesting maternal deposition of these transcripts. All three Aalbtra2 genes were highly expressed in the ovary, while Aalbtra2-β was also highly expressed in the testis. RNAi-mediated knockdown of any or all Aalbtra2 genes did not result in an obvious switch of the sex-specificity in dsx and fru splicing in the whole-body samples. However, knockdown of transcripts from all three tra2 genes significantly reduced the female isoform of dsx mRNA and increased the male isoform of the dsx mRNA in both the ovary and the fat body in adult females. Furthermore, knockdown of either Aalbtra2-α or Aalbtra2-γ or all three Aalbtra2 led to a decrease in ovariole number and ovary size after a blood meal. Taken together, these results indicate that two of the three tra2 genes affect female ovarian development.

Alternative splicing regulation of doublesex gene by RNA-binding proteins in the silkworm Bombyx mori

ABSTRACTDoublesex is highly conserved and sex-specifically spliced in insect sex-determination pathways, and its alternative splicing (AS) is regulated by Transformer, an exonic splicing activator, in the model system of Drosophila melanogaster. However, due to the lack of a transformer gene, AS regulation of doublesex remains unclear in Lepidoptera, which contain the economically important silkworm Bombyx mori and thousands of agricultural pests. Here, we use yeast three-hybrid system to screen for RNA-binding proteins that recognize sex-specific exons 3 and 4 of silkworm doublesex (Bm-dsx); this approach identified BxRBP1/Lark binding to the exon 3, and BxRBP2/TBPH and BxRBP3/Aret binding to the exon 4. Investigation of tissues shows that BxRBP1 and BxRBP2 have no sex specificity, but BxRBP3 has – three of its four isoforms are expressed with a sex-bias. Using novel sex-specific silkworm cell lines, we find that BxRBP1 and BxRBP3 directly interact with each other, and cooperatively function as splicing repressors. Over-expression of BxRBP1 and BxRBP3 isoforms efficiently inhibits splicing of the exons 3 and 4 in the female-specific cells and generates the male-specific isoform of Bm-dsx. We also demonstrate that the sex-determination upstream gene Masc regulates alternatively transcribed BxRBP3 isoforms. Thus, we identify a new regulatory mechanism of doublesex AS in the silkworm, revealing an evolutionary divergence in insect sex-determination.

Cancer-Associated Fibroblasts Induce Epithelial-Mesenchymal Transition in Endometrial Cancer Cells by Regulating Pituitary Tumor Transforming Gene

Cancer-associated fibroblasts (CAFs) play an important role in the development and progression of cancer by inducing epithelial-mesenchymal transition (EMT). In this study, we investigated the role of CAFs in endometrial cancer (EC) cells. We found that the pituitary tumor transforming gene (PTTG) expression was significantly increased in EC cell lines compared to normal human endometrial epithelial cells. Furthermore, CAFs could induce PTTG over-expression and increase EC cell invasion and migration in vitro. In addition, CAFs also induced EMT in EC cells. This study demonstrated that CAFs induced EMT in endometrial cancer cells by regulating PTTG.

The long non-coding RNA PTTG3P promotes growth and metastasis of cervical cancer through PTTG1.

The outgrowth and metastasis of cervical cancer (CC) contribute to its malignancy. Pituitary Tumor Transforming Gene 1 (PTTG1) is upregulated in many types of cancer, and enhances tumor cell growth and metastasis. However, the activation and regulation of PTTG1 in CC, especially by its pseudogene PTTG3P, have not been shown. Here, we detected significantly higher levels of PTTG1 and PTTG3P in the resected CC tissue, compared to the paired adjacent normal cervical tissue. Interestingly, the PTTG3P levels positively correlated with the PTTG1 levels. High PTTG3P levels were associated with poor patients’ survival. In vitro, PTTG1 were increased by PTTG3P overexpression, but was inhibited by PTTG3P depletion in CC cells. However, PTTG3P levels were not altered by modulation of PTTG1 in CC cells, suggesting that PTTG3P is upstream of PTTG1. Moreover, PTTG3P increased CC cell growth, likely through CCNB1-mediated increase in cell proliferation, rather than through decrease in cell apoptosis. Furthermore, PTTG3P increased CC cell invasiveness, likely through upregulation of SNAIL and downregulation of E-cadherin. Our work thus suggests that PTTG3P may promote growth and metastasis of CC through PTTG1.

Exploring molecular tools for transformation and gene expression in the cultivated edible mushroom Agrocybe aegerita.

Agrocybe aegerita is a cultivated edible mushroom in numerous countries, which also serves as a model basidiomycete to study fruiting body formation. Aiming to create an easily expandable customised molecular toolset for transformation and constitutive gene of interest expression, we first created a homologous dominant marker for transformant selection. Progeny monokaryons of the genome-sequenced dikaryon A. aegerita AAE-3 used here were identified as sensitive to the systemic fungicide carboxin. We cloned the wild-type gene encoding the iron-sulphur protein subunit of succinate dehydrogenase AaeSdi1 including its up- and downstream regions, and introduced a single-point mutation (His237 to Leu) to make it confer carboxin resistance. PEG-mediated transformation of protoplasts derived from either oidia or vegetative monokaryotic mycelium with the resulting carboxin resistance marker (CbxR) plasmid pSDI1E3 yielded carboxin-resistant transformants in both cases. Plasmid DNA linearised within the selection marker resulted in transformants with ectopic multiple insertions of plasmid DNA in a head-to-tail repeat-like fashion. When circular plasmid was used, ectopic single integration into the fungal genome was favoured, but also gene conversion at the homologous locus was seen in 1 out of 11 analysed transformants. Employing CbxR as selection marker, two versions of a reporter gene construct were assembled via Golden Gate cloning which allows easy recombination of its modules. These consisted of an eGFP expression cassette controlled by the native promoter PAaeGPDII and the heterologous terminator Tnos, once with and once without an intron in front of the eGFP start codon. After protoplast transformation with either construct as circular plasmid DNA, GFP fluorescence was detected with either transformants, indicating that expression of eGFP is intron-independent in A. aegerita. This paves the way for functional genetics approaches to A. aegerita, e.g., via constitutive expression of fruiting-related genes.

Canine mammary tumour cells exposure to sevoflurane: effects on cell proliferation and neuroepithelial transforming gene 1 expression

ObjectiveThe influence of perioperative factors, such as anaesthetic and analgesic techniques, on metastatic spread following surgery for primary cancer removal is of growing interest. The present study investigated the effects of sevoflurane on canine mammary tumour cell proliferation (MTT colorimetric assay) and on the expression of neuroepithelial transforming gene 1 (NET1). Study designProspective controlled in vitro trial. Study materialPrimary (CIPp) and metastatic canine tubular adenocarcinoma (CIPm) cells. MethodsTo perform MTT tests, cell lines were seeded at a density of 3000 cells per well and incubated with sevoflurane (1, 2.5 or 4 mM) or only with the culture medium (control). Sevoflurane was added to the cell cultures every hour to avoid changes in drug concentration. MTT assays were performed after 6 hours of exposure obtaining absolute values of absorbance. The RNA isolated from the lysates of the same cell lines underwent quantitative polymerase chain reaction to evaluate NET1 gene expression changes compared with controls. One- or two-way analysis of variance was used as appropriate (p < 0.05). ResultsA significant increase in cell proliferation compared with controls was observed in CIPp treated with lower sevoflurane concentrations, whereas a significant decrease in cell proliferation was found in CIPm treated with all the sevoflurane concentrations. All CIPp treatments did not induce changes in gene expression compared with controls, whereas a significant increase in gene expression was observed in CIPm between controls and the higher sevoflurane concentration. Conclusions and clinical relevanceSevoflurane treatments modified the cell proliferation rate in both cell lines showing an increase or decrease when applied to CIPp or CIPm, respectively. Expression of the NET1 gene increased after treatment with sevoflurane 4 mM in metastatic cells. The role of sevoflurane on cancer recurrence should be further investigated.

Efficient somatic and germline genome engineering of Bactrocera dorsalis by the CRISPR/Cas9 system.

Bactrocera dorsalis (Hendel), a very destructive insect pest of many fruits and vegetables, is widespread in many Asian countries. To facilitate control of this pest, it is essential to investigate its genetics and gene function using targeted gene disruption. Here, we describe successful targeted mutagenesis of the white and transformer genes in B. dorsalis through use of the clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR/Cas9) system. Co-injection of the white sgRNA and Cas9 mRNA into B. dorsalis embryos caused eye color change, and the white mutations in the germline were heritable. CRISPR-mediated knockout of the sex determination gene transformer (tra) in B. dorsalis resulted in a male-biased sex ratio and adult flies with abnormal outer and interior reproductive organs. Small indels and substitutions were induced by CRIRPR for both genes. Our data demonstrate that somatic and germline genome engineering of the pest B. dorsalis can be performed efficiently using the CRISPR/Cas9 system, opening the door to the use of the CRISPR-mediated method for functional annotations of genes in B. dorsalis and for its population control using, for example, such as gene drive. © 2018 Society of Chemical Industry.

Molecular Network Basis of Invasive Pituitary Adenoma: A Review.

Cases with pituitary adenoma comprise 10–25% of intracranial neoplasm, being the third most common intracranial tumor, most of the adenomas are considered to be benign. About 35% of pituitary adenomas are invasive. This review summarized the known molecular basis of the invasiveness of pituitary adenomas. The study pointed out that hypoxia-inducible factor-1α, pituitary tumor transforming gene, vascular endothelial growth factor, fibroblast growth factor-2, and matrix metalloproteinases (MMPs, mainly MMP-2, and MMP-9) are core molecules responsible for the invasiveness of pituitary adenomas. The reason is that these molecules have the ability to directly or indirectly induce cell proliferation, epithelial-to-mesenchymal transition, angiogenesis, degradation, and remodeling of extracellular matrix. HIF-1α induced by hypoxia or apoplexy inside the adenoma might be the initiating factor of invasive transformation, followed with angiogenesis for overexpressed VEGF, EMT for overexpressed PTTG, degradation of ECM for overexpressed MMPs, creating a suitable microenvironment within the tumor. Together, they form a complex interactive network. More investigations are required to further elucidate the mechanisms underlying the invasiveness of pituitary adenomas.

Small RNA sequencing reveals dynamic microRNA expression of important nutrient metabolism during development of Camellia oleifera fruit.

To obtain insight into the function of miRNAs in the synthesis and storage of important nutrients during the development of Camellia oleifera fruit, Illumina sequencing of flower and fruit small-RNA was conducted. The results revealed that 797 miRNAs were significantly differentially expressed between flower and fruit samples of Camellia oleifera. Through integrated GO and KEGG function annotations, it was determined that the miRNA target genes were mainly involved in metabolic pathways, plant hormone signal transduction, fruit development, mitosis and regulation of biosynthetic processes. Carbohydrate accumulation genes were differentially regulated by miR156, miR390 and miR395 in the fruit growth and development process. MiR477 is the key miRNA functioning in regulation of genes and involved in fatty acid synthesis. Additionally, miR156 also has the function of regulating glycolysis and nutrient transformation genes.

Pituitary tumor transforming gene binding factor (PBF) is required for androgen-induced prostate cancer proliferation and invasion.

Pituitary tumor transforming gene binding factor (PBF) is a proto-oncogene that plays a role in many cancers; however, its involvement in prostate cancer (PCa) remains unclear. Here, we examined PBF expression in clinical specimens and investigated its regulation and function in human PCa cell lines. Immunohistochemical staining of patient tissues revealed higher PBF expression in PCa than in benign prostatic hyperplasia or adjacent normal prostate specimens. In LNCaP and 22Rv1 cells, PBF expression was upregulated by androgen treatment in a manner partially blocked by the androgen receptor (AR) antagonist bicalutamide. We identified a novel androgen response element in the PBF gene promoter and demonstrated its functional relevance using luciferase reporter assays. Androgen treatment of LNCaP cells induced binding between the endogenous AR and the androgen response element in PBF, as measured by chromatin immunoprecipitation assays. Finally, RNA interference of PBF expression significantly reduced androgen-induced LNCaP cell growth and invasion. Thus, PBF is a novel AR target gene and plays a role in androgen-induced proliferation and metastatic functions in PCa cells.

Ssams2, a Gene Encoding GATA Transcription Factor, Is Required for Appressoria Formation and Chromosome Segregation in Sclerotinia sclerotiorum.

AMS2, a multicopy suppressor for the cpn1 (SpCENP-A) mutant, functions to specifically regulate histone genes transcription and chromosome segregation. As a cell-cycle-regulated GATA transcription factor in eukaryotic organisms, little research has been done on the role of AMS2 protein in pathogenic fungi. In Sclerotinia sclerotiorum, Ssams2 (SS1G_03252) encodes a protein which has been predicted to contain GATA-box domain. Here, Ssams2-silenced strains with significantly reduced Ssams2 gene expression levels exhibited defect in hyphal growth, hyphal branching patterns, compound appressoria differentiation and the oxalic acid production compared to the wild-type (WT) strain. By common bean leaves infection assays, we identified the role of Ssams2 in full virulence. Furthermore, the numbers of cell nucleus in the same length of mycelium in Ssams2-silenced transformants were significantly less than that in the WT strain. The expression levels of histone genes and cell cycle genes in transformants were down-regulated significantly in the RNAi strains. Taken together, our work suggests that the TF SsAMS2 is required for growth, appressoria formation, virulence, and chromosome segregation in S. sclerotiorum.

Oncogenic action of pituitary-tumor transforming gene (PBF) in head and neck cancer is associated with poorer overall survival

Oncogenic action of pituitary-tumor transforming gene (PBF) in head and neck cancer is associated with poorer overall survival

Abstract IA19: MYC activation through enhancer hijacking or focal enhancer amplification drives a subset of high-risk pediatric neuroblastoma

Abstract The amplified MYCN gene serves as an oncogenic driver in approximately 20% of high-risk pediatric neuroblastomas. Here we show that MYC itself is a potent transforming gene in a separate subset of high-risk neuroblastoma cases (~10%), based on (i) its upregulation by focal enhancer amplification or genomic rearrangements leading to enhancer hijacking, and (ii) its ability to transform neuroblastoma precursor cells in a transgenic animal model. The aberrant regulatory elements associated with oncogenic MYC activation include focally amplified distal enhancers or translocation of highly active enhancers from other genes to within topologically associating domains containing the MYC gene locus. The clinical outcome for patients with high levels of MYC expression is virtually identical to that of patients with amplification of the MYCN gene, a known high-risk feature of this disease. Together, these findings establish MYC as a bona fide oncogene in a clinically significant group of high-risk childhood neuroblastomas. Citation Format: Mark W. Zimmerman, Yu Liu, Shuning He, Adam D. Durbin, Brian J. Abraham, John Easton, Ying Shao, Beisi Xu, Shizhen Zhu, Xiaoling Zhang, Nina Weichert-Leahey, Richard A. Young, Jinghui Zhang, A. Thomas Look. MYC activation through enhancer hijacking or focal enhancer amplification drives a subset of high-risk pediatric neuroblastoma [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr IA19.

Expression of pituitary transforming gene 1 in renal clear cell carcinoma and its association with prognosis

Objective To inyestigate the expression of pituitary transforming gene 1 (PTTG1) in renal clear cell carcinoma (RCCC) tissues and explore its association with the prognosis. Methods PTTG1 mRNA and protein levels were assessed in 41 paired RCCC tissues and adjacent normal tissues by real-time fluorescent quantitative polymerase chain reaction (FQ-PCR) and immunohistochemistry respectively. Further immunohistochemical analysis was implemented in 89 samples of RCCC to evaluate the associations between PTTG1 levels and the clinical characteristics in RCCC. Results FQ-PCR and immunohistochemical analysis demonstrated that the PTTG1 mRNA and protein levels were significantly higher in RCCC compared to normal tissues (P=0.007). In addition, the PTTG1 protein level in 89 RCCC samples was found to be significantly correlated with Fuhrman grade (P=0.026) and TNM stage (P=0.031), whereas it was not associated with gender (P=0.123), age (P=0.338) and recurrence (P=0.285). The five-year survival rate was 35.3% and 72.7% in patients with high and low PTTG1 levels respectively. The survival time of RCCC patients with high PTTG1 level was significantly lower than those with low PTTG1 1evel (P=0.029). Conclusion The overexpression of PTTG1 indicates a poor prognosis in RCCC patients and, therefore, PTTG1 may serve as a novel prognostic marker for RCCC. Key words: Pituitary transforming gene 1; Renal clear cell carcinoma; Survival rate; Prognosis

The mRNA expression of PTTG1 is a strong prognostic indicator for recurrence after hypophysectomy in dogs with corticotroph pituitary adenomas

Pituitary-dependent hypercortisolism (PDH) is a common endocrinopathy in dogs, but the promotors and initiators of the tumourigenesis of corticotroph pituitary adenomas remain unknown. Based on human data, we investigated mRNA expression of pituitary tumour transforming gene 1 (PTTG1) with quantitative RT-PCR in canine corticotroph pituitary adenomas. PTTG1 was overexpressed in adenomas approximately 3-fold. A strong association was observed between PTTG1 expression and disease-free interval; dogs with high PTTG1 expression had a significantly (4 times; P=0.02) shorter disease-free interval than dogs with low PTTG1 expression. This paper shows that PTTG1 expression is a negative prognosticator in relation to disease-free interval and recurrence in dogs undergoing transsphenoidal hypophysectomy as treatment for PDH.