The analyses of SRCR genes based on protein-protein interaction network in esophageal squamous cell carcinoma
AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH
Authors: Du, Zepeng; Xia, Qiaoxi; Wu, Bingli; Ding, Jiyu; Zhao, Yan; Lin, Ling; Chen, Mantong; Cai, Zhixiong; Wang, Shaohong; Xu, Liyan; Li, Enmin; Wu, Zhiyong; Li, Yun; Xu, Haixiong; Yin, Dong
Abstract
The scavenger receptor cysteine-rich (SRCR) proteins, with one to several SRCR domains, play important roles in human diseases. A full view of their functions in esophageal squamous cell carcinoma (ESCC) remain unclear. Sequence alignment and phylogenctic tree for all human SRCR domains were performed. Differentially-expressed SRCR genes were identified in ESCC, followed by protein-protein interaction (PPI) network construction, topological parameters, subcellular distribution, functional enrichment and survival analyses. The variation of conserved cysteines in each SRCR domain suggested a requirement for new classification of the SRCR family. Six genes (LGALS3BP, MSR1, CD163, LOXL2, LOXL3 and LOXL4) were upregulated, and four genes (DMBT1, PRSS12, TMPRSS2 and SCARA5) were downregulated in ESCC. These 10 SRCR genes form a unique biological network. Functional enrichment analyses provided important clues to investigate the biological functions for SRCR gene network in ESCC, such as extracellular structure organization and the PI3K-Akt signaling pathway. Kaplan-Meier curves confirmed that high expression of SCARA5, LOXL2, LOXL3, LOXL4 were related to poor survival, whereas high expression of DMBTI and PRSS12 showed the opposite result. SRCR genes promote the development of ESCC through its network and could serve as potential prognostic factors and therapy targets of ESCC.
Distribution and prognostic impact of microglia/macrophage subpopulations in gliomas
BRAIN PATHOLOGY
Authors: Zeiner, Pia S.; Preusse, Corinna; Golebiewska, Anna; Zinke, Jenny; Iriondo, Ane; Muller, Arnaud; Kaoma, Tony; Filipski, Katharina; Mueller-Eschner, Monika; Bernatz, Simon; Blank, Anna-Eva; Baumgarten, Peter; Ilina, Elena; Grote, Anne; Hansmann, Martin L.; Verhoff, Marcel A.; Franz, Kea; Feuerhake, Friedrich; Steinbach, Joachim P.; Wischhusen, Joerg; Stenzel, Werner; Niclou, Simone P.; Harter, Patrick N.; Mittelbronn, Michel
Abstract
While the central nervous system is considered an immunoprivileged site and brain tumors display immunosuppressive features, both innate and adaptive immune responses affect glioblastoma (GBM) growth and treatment resistance. However, the impact of the major immune cell population in gliomas, represented by glioma-associated microglia/macrophages (GAMs), on patients' clinical course is still unclear. Thus, we aimed at assessing the immunohistochemical expression of selected microglia and macrophage markers in 344 gliomas (including gliomas from WHO grade I-IV). Furthermore, we analyzed a cohort of 241 IDH1R132H-non-mutant GBM patients for association of GAM subtypes and patient overall survival. Phenotypical properties of GAMs, isolated from high-grade astrocytomas by CD11b-based magnetic cell sorting, were analyzed by immunocytochemistry, mRNA microarray, qRT-PCR and bioinformatic analyses. A higher amount of CD68-, CD163- and CD206-positive GAMs in the vital tumor core was associated with beneficial patient survival. The mRNA expression profile of GAMs displayed an upregulation of factors that are considered as pro-inflammatory M1 (eg, CCL2, CCL3L3, CCL4, PTGS2) and anti-inflammatory M2 polarization markers (eg, MRC1, LGMN, CD163, IL10, MSR1), the latter rather being associated with phagocytic functions in the GBM microenvironment. In summary, we present evidence that human GBMs contain mixed M1/M2-like polarized GAMs and that the levels of different GAM subpopulations in the tumor core are positively associated with overall survival of patients with IDH1R132H-non-mutant GBMs.