scholarly journals High expression of C-X-C chemokine receptor 4 and Notch1 is predictive of lymphovascular invasion and poor prognosis in lung adenocarcinoma

Tumor Biology ◽  
2017 ◽  
Vol 39 (6) ◽  
pp. 101042831770869 ◽  
Author(s):  
Zhuangzhuang Cong ◽  
Haiwei Wu ◽  
Zhong Guo ◽  
Tao Qin ◽  
Yang Xu ◽  
...  
2021 ◽  
Vol 11 ◽  
Author(s):  
Yi Zheng ◽  
Shiying Hao ◽  
Cheng Xiang ◽  
Yaguang Han ◽  
Yanhong Shang ◽  
...  

BackgroundImmune checkpoint inhibitors have achieved breakthrough efficacy in treating lung adenocarcinoma (LUAD) with wild-type epidermal growth factor receptor (EGFR), leading to the revision of the treatment guidelines. However, most patients with EGFR mutation are resistant to immunotherapy. It is particularly important to study the differences in tumor microenvironment (TME) between patients with and without EGFR mutation. However, relevant research has not been reported. Our previous study showed that secreted phosphoprotein 1 (SPP1) promotes macrophage M2 polarization and PD-L1 expression in LUAD, which may influence response to immunotherapy. Here, we assessed the role of SPP1 in different populations and its effects on the TME.MethodsWe compared the expression of SPP1 in LUAD tumor and normal tissues, and in samples with wild-type and mutant EGFR. We also evaluated the influence of SPP1 on survival. The LUAD data sets were downloaded from TCGA and CPTAC databases. Clinicopathologic characteristics associated with overall survival in TCGA were assessed using Cox regression analysis. GSEA revealed that several fundamental signaling pathways were enriched in the high SPP1 expression group. We applied CIBERSORT and xCell to calculate the proportion and abundance of tumor-infiltrating immune cells (TICs) in LUAD, and compared the differences in patients with high or low SPP1 expression and wild-type or mutant EGFR. In addition, we explored the correlation between SPP1 and CD276 for different groups.ResultsSPP1 expression was higher in LUAD tumor tissues and in people with EGFR mutation. High SPP1 expression was associated with poor prognosis. Univariate and multivariate cox analysis revealed that up-regulated SPP1 expression was independent indicator of poor prognosis. GSEA showed that the SPP1 high expression group was mainly enriched in immunosuppressed pathways. In the SPP1 high expression group, the infiltration of CD8+ T cells was lower and M2-type macrophages was higher. These results were also observed in patients with EGFR mutation. Furthermore, we found that the SPP1 expression was positively correlated with CD276, especially in patients with EGFR mutation.ConclusionSPP1 levels might be a useful marker of immunosuppression in patients with EGFR mutation, and could offer insight for therapeutics.


Aging ◽  
2020 ◽  
Author(s):  
Cheng-Yu Jin ◽  
Liang Du ◽  
A-Han Nuerlan ◽  
Xiao-Lei Wang ◽  
Yong-Wei Yang ◽  
...  

2020 ◽  
Author(s):  
Zhaona Sun ◽  
Meiyuan Chen ◽  
Ziping Li ◽  
Hong Zhang

Abstract BackgroundMore recently, E3 ubiquitin ligases are well-informed to be involved in tumor development, and genetic aberration of this family have been implicated in breast cancer and oral cancer. RING finger protein 126 (RNF126), a newly uncovered E3 ubiquitin ligase, targets multiple proteins to promote their degradation. This study aims to explore the expression pattern and functional role of RNF126 in lung adenocarcinoma (LAD). MethodsImmunohistochemical staining and real-time PCR were used to evaluate the expression pattern of RNF126 in normal lung tissue and LAD tissues. Western blot, cell proliferation and invasion assays were performed to investigate role of RNF126 in modulating LAD progression. Statistical analyses including Chi-square test, Kaplan-Meier test, Cox regression test, and Student’s t-test were conducted for both clinical and experimental data.ResultsWe find that both the mRNA and protein expression levels of RNF126 are elevated in LAD tissues, and its expression correlates with clinicopathologic features including tumor size and TNM stage. High expression of RNF126 indicates a poor prognosis of LAD patients. Gene perturbations reveal that RNF126 promotes LAD cells proliferation and xenograft growth. However, RNF126 exerts no significant effect on cell migration and invasion in LAD cells. ConclusionsOur clinical and cellular data suggest that targeting this molecule could potentially provide advantages for LAD patients with high expression of RNF126.


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