Expression and clinical significance of absent in melanoma 2 in colorectal cancer
BIOMEDICINE & PHARMACOTHERAPY
Authors: Zhang, Zhi; Dong, Xiaoqiang; Yang, Xiaodong; Wan, Daiwei; Sun, Liang; Gu, Mengmeng; Li, Ming; Zhu, Zheng; Wang, Jin; Shang, Zengfu; He, Songbing
Abstract
Increasing research has indicated that absent in melanoma 2 (AIM2) is aberrantly expressed in several tumor types. However, the association between AIM2 expression and clinicopathological factors or prognosis of patient with colorectal cancer (CRC) remains elusive. In the present study, we first examined the protein and mRNA expression of AIM2 in CRC cell lines by western blotting and quantitative RT-PCR (qRT-PCR). Then, we detected AIM2 expression in CRC tissue using western blotting and immunohistochemistry (IHC) respectively to evaluate its clinicopathological characteristics and prognosis in CRC. Our cytological experiments showed that there was low AIM2 expression in most of the CRC cell lines. Western blotting and IHC indicated that AIM2 expression was obviously lower in the primary CRC tissue than the adjacent normal tissue (P < 0.01 and P < 0.001). Clinicopathological analysis revealed that low AIM2 expression was significantly associated with some clinicopathological features such as depth of invasion (P = 0.020), TNM clinical stage (P = 0.013) and lymph node metastasis (P = 0.026). Spearman analysis indicated that there was a negative correlation between AIM2 expression and preoperative serum carcino-embryonic antigen (CEA) levels in CRC patients (r = -0.217, P = 0.009). Moreover, Kaplan-Meier analysis showed that low expression of AIM2 could lead to a significantly shorter overall survival rate (P = 0.001). Cox's proportional hazards model also indicated that the low expression of AIM2 could serve as an independent and significant prognostic factor for survival. Taken together, our findings identify AIM2 as a valuable biomarker for prognosis and a potential therapeutic target for CRC. (C) 2017 Published by Elsevier Masson SAS.
The Central Role and Possible Mechanisms of Bacterial DNAs in Sepsis Development
MEDIATORS OF INFLAMMATION
Authors: Cheng, Zhenxing; Abrams, Simon T.; Austin, James; Toh, Julien; Wang, Susan Siyu; Wang, Zhi; Yu, Qian; Yu, Weiping; Toh, Cheng Hock; Wang, Guozheng
Abstract
The pathological roles of bacterial DNA have been documented many decades ago. Bacterial DNAs are different from mammalian DNAs; the latter are heavily methylated. Mammalian cells have sensors such as TLR-9 to sense the DNAs with nonmethylated CpGs and distinguish them from host DNAs with methylated CpGs. Further investigation has identified many other types of DNA sensors distributed in a variety of cellular compartments. These sensors not only sense foreign DNAs, including bacterial and viral DNAs, but also sense damaged DNAs from the host cells. The major downstream signalling pathways includeTLR-9-MyD88-IKKa-IRF-7/NF-kappa B pathways to increase IFN/proinflammatory cytokine production, STING-TBK1-IRF3 pathway to increase IFN-beta, and AIM2-ASC-caspas-1 pathway to release IL-1beta. The major outcome is to activate host immune response by inducing cytokine production. In this review, we focus on the roles and potential mechanisms of DNA sensors and downstream pathways in sepsis. Although bacterial DNAs play important roles in sepsis development, bacterial DNAs alone are unable to cause severe disease nor lead to death. Priming animals with bacterial DNAs facilitate other pathological factors, such as LPS and other virulent factors, to induce severe disease and lethality. We also discuss compartmental distribution of DNA sensors and pathological significance as well as the transport of extracellular DNAs into cells. Understanding the roles of DNA sensors and signal pathways will pave the way for novel therapeutic strategies in many diseases, particularly in sepsis.