CXCL1 as an Unfavorable Prognosis Factor Negatively Regulated by DACH1 in Non-small Cell Lung Cancer
FRONTIERS IN ONCOLOGY
Authors: Yu, Shengnan; Yi, Ming; Xu, Linping; Qin, Shuang; Li, Anping; Wu, Kongming
Abstract
Background: Interaction between cancer cells with microenvironment is essential for cancer progression, therapeutic resistance and prognosis. Chemokine CXCL1 shows variable roles in the development of cancers. DACH1 has been considered as a tumor suppressor and represses the expressions of several chemokines. The relationship between CXCL1 and DACH1 in non-small cell lung cancer (SCLC) deserves further investigation. Methods: Immunohistochemistry staining was performed on tumor tissue microarrays from lung cancer patients to detect CXCL1 protein. The CXCL1 concentration in the serum of adenocarcinoma patients was measured by ELISA. The CXCL1 protein secreted by cancer cell lines was detected by SearchLight proteome array and human cytokine antibody array. The meta-analysis of CXCL1 expression form public databases was performed and correlation between CXCL1 and DACH1 was analyzed. Moreover, the association between clinicopathological features and prognosis with CXCL1 and DACH1 was analyzed by tissue array and KM-plotter from public database. Results: The protein abundance of CXCL1 in lung cancer tissues was significantly higher than that in adjacent normal tissues. CXCL1 was closely related to TNM stage, tumor size, and lymph node metastasis and predicted worse overall survival in adenocarcinoma. The level of CXCL1 in the peripheral blood of adenocarcinoma patients also significantly elevated and positively related with clinical stage. The meta-analysis demonstrated that CXCL1 mRNA level was increased in lung cancer tissues and high level of CXCL1 indicated tumor progression in lung adenocarcinoma. In addition, public database analyses showed that CXCL1 negatively correlated with DACH1. Stable overexpressing DACH1 in cultured lung cancer cells remarkably decreased CXCL1 protein. Moreover, ectopic expression of DACH1 significantly inhibited the expression of CXCL1, Ki67, and cyclin D1 in tumor tissues compared with A549 cells with empty vector. Survival analysis showed that high CXCL1 and low DACH1 indicated poor overall survival and progression-free survival. Conclusion: CXCL1 is closely associated with tumor progression and poor survival. DACH1 significantly inhibits the expression of CXCL1 and indicates good prognosis. Therefore, combined detection of CXCL1 and DACH1 could more precisely predict prognosis of lung adenocarcinoma.
Identification and characterization of three CXC chemokines in Asian swamp eel (Monopterus albus) uncovers a third CXCL11_like group in fish
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
Authors: Yuan, Hanwen; Li, Youshen; Han, Panpan; Tian, Guangming; Zhang, Wenbing; Guo, Huizhi; Xu, Qiaoqing; Wang, Tiehui
Abstract
Chemokines direct cell migration in development and immune defense, and bridge between innate and adaptive immune responses. The chemokine gene family has been rapidly evolving and has undergone species/lineage-specific expansion. Mammals possess inflammatory CXC chemokines CXCL1-8/15 and CXCL9-11 sub-groups, and homeostatic CXCL12-14, 16-17. Orthologues of mammalian CXCL12-14, three chemokines related to CXCL1-8/15 (CXCL8_L1-3), two chemokines related to CXC9-11 (CXCL11_L1-2), and five fish-specific chemokines (CXCL_F1-5) have been described in teleosts. In this study, we reported three novel CXC chemokines in Asian swamp eel Monopterus albus, a commercially important freshwater fish species in China. Two of them belong to the fish-specific CXCL_F2 group, named CXCL_F2a/b, that share 89.5% amino acid identity. The other (CXCL11_L3) belongs to a third CXCL11_L related to the mammalian CXCL9-11 subfamily found only in percomorph fish species, and is the only CXCL9-11 related molecules in this lineage. Mammalian CXCL9.11 attract Th1 cells, and block the migration of Th2 cells in an immune response. This study suggests that all major lineages of teleosts have a CXCL9-11 related chemokine that will aid future functional investigation of CXCL11_L in fish. Cxcl_f2a is highly expressed constitutively in the skin of swamp eels that may attract immune cells to protect the skin in the absence of scales. Cxcl11_l3 and cxcl_f2b are highly expressed in immune tissues/organs and are up regulated by the viral mimic poly I:C, but not bacterial infection in vivo, suggesting their role in anti-viral defense. The two cxcl_f2 paralogues are differentially expressed and modulated, indicating sub- and/or neofunctionalization.