High Expression of Complement Component C7 Indicates Poor Prognosis of Endometrial Cancer and poor 5-year OS

Background: Corpus Carcinoma is the most commonly diagnosed female cancer worldwide. However, the well-known biomarkers are not enough to meet the needs of precision medicine. Novel targets are desirable and highly valuable for improved patient survival. In this regard, we identified complement component C7 as one of the candidates based on data from the TCGA database.Method: C7 expression was examined by mRNA expression profile in 425 cases of corpus carcinoma, including grade 3 data (such as mRNA-seq, miRNA-seq, and clinical data) from 406 primary corpus carcinoma tissues and 19 normal controls from the dataset. The availability of data is demonstrated by heat maps, and the distribution of genes is demonstrated by volcanic maps. Then the value of C7 was demonstrated on the basis of genomics and clinical epidemiology respectively, confirmed by grade 3 data from TCGA. The relationship between the C7 expression and five-year survival of corpus carcinoma patients was analyzed in order to investigate the function of C7 in corpus carcinoma. Result: In our present study, we reported for the first time that C7 was an independent prognostic factor of corpus carcinoma and the 5-year survival rate of patients with high C7 expression is lower than that of patients with low C7 expressions. (p=0.02265) Conclusion: In summary, high expression of C7 may promote corpus carcinoma development. Our present study laid a foundation to help clinicians improve the identification of patients for C7 in the era of precision medicine.

Identification of lncRNA and mRNA Expression Profile in Relapsed Graves’ Disease

Background: Graves’ disease (GD) is a common autoimmune disease, and its pathogenesis is unclear. Studies have found that the occurrence of GD is related to the immune disorder caused by the interaction of genetic susceptibility and environmental factors. The CD4+ T cell subset is closely related to the immune disorder of GD. LncRNAs are RNA molecules with a length of more than 200 nt and are involved in a variety of autoimmune diseases. However, the roles of lncRNAs in recurrent GD are still elusive. The purpose of this study is to identify lncRNA and mRNA expression profile in relapsed Graves’ disease.Method: CD4+ T cells from 12 recurrent GD and 8 healthy controls were collected for high-throughput sequencing. The gene-weighted co-expression network analysis (WGCNA) was used to construct the co-expression module relevant to recurrent GD, and the key genes in the module were verified by RT-PCR.Results: There are 602 upregulated lncRNAs and 734 downregulated lncRNAs in CD4+ T cells in recurrent GD patients compared with the healthy controls. The module most relevant to GD recurrence was constructed using WGCNA, and the key genes in the module were verified by RT-PCR. We found that the expression of RPL8, OAS2, NFAT5, DROSHA, NONHSAT093153.2, NONHSAT118924.2, and NONHSAT209004.1 was significantly decreased in GD group (p < 0.001, p < 0.001, p < 0.01, p < 0.05, p < 0.001, p < 0.05, and p < 0.01, respectively).Conclusion: LncRNAs are closely related to the recurrence of GD. For the first time, we constructed the expression profile of lncRNAs and mRNAs in CD4+ T cells in recurrent GD patients.

P–076 Probability of sperm retrieval in azoospermic patients and mRNA expression profile of JMJD1A, TNP2 and PRM2 : in a subset of karachi population

Study question To access successfulness of sperm retrieval by evaluating the mRNA expression profile of JMJD1A, TNP1, TNP2, PRM1 and PRM2 in patients undergoing surgical sperm retrieval procedure. Summary answer Probability of sperm retrieval in azoospermia is decreased when mRNA expression profile of JMJD1A TNP2 and PRM2 in testicular tissue is decreased. What is known already Studies have been done on expression of JMJD1A in non-obstructive azoospermic patients in other part of the world with smaller sample size but this is the first study in Pakistan with larger number of patients. Study design, size, duration: Crossectional study, 100 azoospermic patients coming for purpose of sperm retrieval by TESE or micro-TESE in Australian Concept Infertility Medical Center, Karachi,from March, 2018 to December, 2019 Participants/materials, setting, methods All recruited azoospermic patients were evaluated by history, physical examination, and hormonal assessment. RNA was extracted by pureLink RNA Micro kit and mRNA expression of the JMJD1A, TNP1, TNP2, PRM1 and PRM2 genes was determined using innu-SCRIPT One Step RT_qPCR SyGreen kit. For quantitative variables independent t test and for categorical variables chi-square/ Fisher Exact test was used. Unadjusted and adjusted prevalence ratio were reported by using cox regression algorithm. Main results and the role of chance: The patients were categorized into (i) Group-I: Patients with successful sperm retrieval n = 42, (ii) Group-II: Patients with unsuccessful sperm retrieval n = 58. The patients were categorized into (i) Group-I: Patients with successful sperm retrieval n = 42, (ii) Group-II: Patients with unsuccessful sperm retrieval n = 58. Azoospermic men in the successful sperm retrieval group had significantly decreased expression of JMJD1A (P < 0.001), TNP2(P < 0.001), and PRM2 (P 0.008). In addition to this regarding hormonal parameters: FSH (P 0.004), LH(P < 0.001), TSH(P<.011) were significantly different in azoospermic men with successful and unsuccessful sperm retrieval. In multivariate analysis, after adjusting for the other covariates, a significant association was found between JMJD1A, TNP2, PRM2 and successful sperm retrieval (p-value <0.05). Limitations, reasons for caution It is unicentric and outcomes for fertilization were not assessed. Azoospermic patients from multi-centeres were difficult because of lack of facility of sperm retrieval procedures at these centers and it was difficult to follow the fertrilization outcome. Wider implications of the findings: This will be useful for making the decision in azoospermic men to proceed for ICSI or not. In addition to this, the repetition of unnecessary surgical procedures can be avoided, as the azoospermic men often undergo number of rounds of ICSI, with the hope of becoming biological father. Trial registration number non-clinical trials

Prostaglandin F2α agonists induced enhancement in collagen1 expression is involved in the pathogenesis of the deepening of upper eyelid sulcus

Previous our study reported that three-dimension (3D) cultures of human orbital fibroblasts (HOFs) replicated the etiology of deepening of the upper eyelid sulcus (DUES) caused by prostaglandin F2α analogues (PGF2α-ags). To examine this further, the effects of PGF2α-ags on HOFs were characterized by (1) lipid staining (2D; two-dimension, 3D), (2) comparison of the 3D organoid sizes of preadipocytes (DIF−) or adipocytes (DIF+) that had been treated with various concentrations of several PGF2α-ags, (3) physical stiffness (3D), and (4) the mRNA expression of adipogenic related genes, extracellular matrix (ECM), tissue inhibitors of metalloproteinases (TIMPs) and matrix metalloproteinases (MMPs) (3D). PGF2α-ags caused a dramatic down-sizing of the 3D DIF+ organoids and this reduction was concentration dependent. The effects caused by PGF2α-ags were also observed in 3D preadipocytes. Micro-squeezer analysis clearly indicated that PGF2α-ags induced an increase in their physical solidity. The size of each organoid under several conditions was inversely correlated with the mRNA expression profile of collagen1 (COL1), TIMP2, and MMP2 and 9. These findings indicate that PGF2α-ags affect the expression of COL1, TIMP2, and MMP2 and 9 which, in turn, modulate the 3D ECM network within the organoids, thus resulting in their downsizing.

Integrating transcriptome-wide association study and mRNA expression profile identified candidate genes related to hand osteoarthritis

Background Osteoarthritis (OA) is a common skeletal system disease that has been partially attributed to genetic factors. The hand is frequently affected, which seriously affects the patient’s quality of life. However, the pathogenetic mechanism of hand osteoarthritis (hand OA) is still elusive. Methods A genome-wide association study (GWAS) summary of hand OA was obtained from the UK Biobank dataset, which contains data from a total of 452,264 White British individuals, including 37,782 OA patients. The transcriptome-wide association study (TWAS) of hand OA was performed using FUnctional Summary-based ImputatiON (FUSION) with the skeletal muscle and blood as gene expression references. The significant genes identified by TWAS were further subjected to gene set enrichment analysis (GSEA) with the Database for Annotation, Visualization and Integrated Discovery (DAVID) tool. Furthermore, we compared the genes and gene sets identified by our TWAS with that of a knee OA mRNA expression profile to detect the genes and gene sets shared by TWAS and mRNA expression profiles in OA. The mRNA expression profiles of 18 normal knee cartilages and 20 OA knee cartilages were acquired from the Gene Expression Omnibus database (accession number: GSE114007). Results TWAS identified 177 genes with P < 0.05 for the skeletal muscle, including ANKRD44 (P = 0.0001), RIC3 (P = 0.0003), and AC005154.6 (P = 0.0004). TWAS identified 423 genes with P < 0.05 for the blood, including CRIM1 (P = 0.0002), ZNF880 (P = 0.0002), and NCKIPSD (P = 0.0003). After comparing the results of the TWAS to those of the mRNA expression profiling of OA, we identified 5 common genes, including DHRS3 (log2fold = − 1.85, P = 3.31 × 10− 9) and SKP2 (log2fold = 1.36, P = 1.62 × 10− 8). GSEA of TWAS identified 51 gene ontology (GO) terms for hand OA, for example, protein binding (P = 0.0003) and cytosol (P = 0.0020). We also detected 6 common GO terms shared by TWAS and mRNA expression profiling, including protein binding (PTWAS = 2.54 × 10− 4, PmRNA = 3.42 × 10− 8), extracellular exosome (PTWAS = 0.02, PmRNA = 1.18 × 10− 4), and cytoplasm (PTWAS = 0.0183, PmRNA = 0.0048). Conclusion In this study, we identified 5 candidate genes and 6 GO terms related to hand OA, which may help to uncover the pathogenesis of hand OA. It should be noted that the possible difference in the gene expression profiles between hand OA and knee OA may affect our study results, which should be interpreted with caution.