Identification of significant gene biomarkers of low back pain caused by changes in the osmotic pressure of nucleus pulposus cells
SCIENTIFIC REPORTS
Authors: Zhao, Changsong; Quan, Xuemin; He, Jie; Zhao, Rugang; Zhang, Yao; Li, Xin; Sun, Sheng; Ma, Rui; Zhang, Qiang
Abstract
The incidence of intervertebral disc (IVD) degeneration disease, caused by changes in the osmotic pressure of nucleus pulposus (NP) cells, increases with age. In general, low back pain is associated with IVD degeneration. However, the mechanism and molecular target of low back pain have not been elucidated, and there are no data suggesting specific biomarkers of low back pain. Therefore, the research aims to identify and verify the significant gene biomarkers of low back pain. The differentially expressed genes (DEGs) were screened in the Gene Expression Omnibus (GEO) database, and the identification and analysis of significant gene biomarkers were also performed with various bioinformatics programs. A total of 120 patients with low back pain were recruited. Before surgery, the degree of pain was measured by the numeric rating scale (NRS), which enables comparison of the pain scores from individuals. After surgery, IVD tissues were obtained, and NP cells were isolated. The NP cells were cultured in two various osmotic media, including iso-osmotic media (293 mOsm/kg H2O) to account for the morbid environment of NP cells in IVD degeneration disease and hyper-osmotic media (450 mOsm/kg H2O) to account for the normal condition of NP cells in healthy individuals. The relative mRNA expression levels of CCL5, OPRL1, CXCL13, and SST were measured by quantitative real-time PCR in the in vitro analysis of the osmotic pressure experiments. Finally, correlation analysis and a neural network module were employed to explore the linkage between significant gene biomarkers and pain. A total of 371 DEGs were identified, including 128 downregulated genes and 243 upregulated genes. Furthermore, the four genes (CCL5, OPRL1, SST, and CXCL13) were identified as significant gene biomarkers of low back pain (P < 0.001) based on univariate linear regression, and CCL5 (odds ratio, 34.667; P = 0.003) and OPRL1 (odds ratio, 19.875; P < 0.001) were significantly related to low back pain through multivariate logistic regression. The expression of CCL5 and OPRL1 might be correlated with low back pain in patients with IVD degeneration disease caused by changes in the osmotic pressure of NP cells.
Extent and characteristics of immune infiltration in clear cell renal cell carcinoma and the prognostic value
TRANSLATIONAL ANDROLOGY AND UROLOGY
Authors: Wang, Yuhao; Yang, Jie; Zhang, Qijie; Xia, Jiadong; Wang, Zengjun
Abstract
Background: Immune infiltration has an important impact on the development of clear cell renal cell carcinoma (ccRCC). This article aims to investigate the association between immune infiltration and the clinical features as well as prognosis of clear cell renal cell carcinoma. Methods: Analyze the immune infiltration in ccRCC by applying ESTIMATE and CIBERSORT methods on basic of dataset in TCGA and GEO. And identify the kind of immune cell and genes that may play the central role. Results: High Immune score and high property of T-regs are both significantly associated with the poor OS, high stage and more chances of metastases in ccRCC. CXCL-1, SAA1, PMCH, CCL-5 are all significantly negatively correlated to OS and positively correlated to stage and chance of metastases in ccRCC. High property of T- regs, CXCL-1 and SAA1 are also significantly associated with high Fuhrman grade while PMCH and CCL5 not. Conclusions: Immune infiltration in RCC has a negative influence on ccRCC and T-regs may play a vital role in this process mediated by CXCL-1 or SSA1.