Epigenetic silencing of chemokine CCL2 represses macrophage infiltration to potentiate tumor development in small cell lung cancer

e13128 Background: With the development of targeted drugs, there are more therapeutic options for patients with non-small cell lung cancer (NSCLC) harboring corresponding genetic alterations. However, cancers are frequently caused by alterations on multiple genes, which collaborate to promote tumor development. Methods: A total of 1353 NSCLC patients from five different clinical institutions were enrolled in this study. Concurrent DNA and RNA NGS analysis was performed using the Ion Ampliseq Colon and Lung Cancer gene panel v2 and the AmpliSeq RNA Lung Cancer Research Fusion Panel using FFPE samples from surgically resected NSCLC tumors. Results: Of the 1293 mutations that were detected, 2338 variants were identified in 24 genes, while 27 of the tumor samples were identified to have co-occurring DNA mutations (including insertions, deletions and point mutations) and RNA fusion mutations. Analysis of the 975 patients with EGFR-gene mutations revealed that the incidence of dual EGFR L858R/T790M mutations were higher compared to EGFR 19del/T790M, and the MAF of T790M was lower compared to 19del in dual EGFR 19del/T790M patients. Conclusions: Even with the non-random cohort of patients in this study, the genetic alterations detected in this study had a certain degree of representation of NSCLC (especially lung adenocarcinoma) in the Chinese population. The differences in the MAF of EGFR T790M may determine different responses to TKI therapy in patients harboring dual mutations.

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Investigation on Potential Correlation Between the RNA-Binding Protein of Evolutionarily Conserved MEX3 Family and Non–Small-Cell Lung Cancer

10.21203/rs.3.rs-800392/v1 ◽

2021 ◽

Author(s):

Ming Zhang ◽

Hualiang Zhang ◽

Linfeng Cao ◽

Gouxin Hou ◽

Chao Lu ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Rna Binding ◽

Immune Cell ◽

Tumor Development ◽

Treatment Strategies ◽

Small Cell ◽

Small Cell Lung ◽

Tumor Cell Death

Abstract Background As mRNA binding proteins, MEX3 (muscle excess 3) family highlights its unique characteristics and plays an emerging role in post-transcriptionally regulating programmed of biological processes, including tumor cell death and immunological relevance. These have been shown to be involved in various diseases, however, the role of MEX3 in non-small-cell lung cancer (NSCLC) has not been fully elucidated. Results In this study, we found that the sequence or copy number of MEX3 gene did not change significantly, which can explain the stability of malignant tumor development through the COSMIC database. Further, gene expression in NSCLC was examined using the Oncomine™ database, and the prognostic value of each gene was analyzed by Kaplan-Meier analysis. The results showed that overexpressed of MEX3A, MEX3B, MEX3C and MEX3D were associated with significantly lower OS in patients with NSCLC and LUAD, while overexpressed of MEX3D was associated with significantly poorer OS in patients with LUSC. We also applied the Tumor Immune Estimation Resource (TIMER) tool to assess the correlations between distinct MEX3 and the infiltrating immune cell landscape. Conclusion On this subject, we have learned about the complexity and heterogeneity of NSCLC through MEX3. We found that most of MEX3 is highly expressed in NSCLC. High expression indicates a poor prognosis and has a certain immune correlation. Therefore, these conclusions can lay a framework for the prognosis of NSCLC patients and the development of treatment strategies in the future.

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