scholarly journals RAB11FIP1: An Indicator for Tumor Immune Microenvironment and Prognosis of Lung Adenocarcinoma from a Comprehensive Analysis of Bioinformatics

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenyi Zhang ◽  
Ting Chen ◽  
Jun Liu ◽  
Shali Yu ◽  
Lei Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Network Analysis ◽  
Lung Adenocarcinoma ◽  
Protein Interactions ◽  
Potential Mechanism ◽  
Protein Protein Interactions ◽  
Immune Markers ◽  
Immune Microenvironment ◽  
Kaplan Meier ◽  
Tumor Immune Microenvironment

Lung adenocarcinoma (LUAD) was the first one all over the world. RAB11FIP1 was found to be expressed differently in a critical way among different cancers. However, the prognostic value and immune infiltration of RAB11FIP1 expression in LUAD are unclear. In this study, the expression of RAB11FIP1 in LUAD was investigated in the Oncomine, TCGA, GEO, and UALCAN databases. Kaplan-Meier analysis was chosen to compare the association between RAB11FIP1 expression and overall survival (OS) in LUAD patients. The dataset of TCGA was used to analyze the pertinence between RAB11FIP1 and clinicpathological factors. GO, KEGG, and network analysis of protein-protein interactions (PPI) were conducted to investigate the potential mechanism of RAB11FIP1. In the end, the relevance of RAB11FIP1 to cancer-immune infiltrates was investigated. RAB11FIP1 was found to be down-regulated by tumors compared with adjacent normal tissue in multiple LUAD cohorts. RAB11FIP1 is an independent prognostic factor in lung adenocarcinoma. There was a high correlation between low RAB11FIP1 in tumors and worse OS in LUAD. Functional network analysis suggested that RAB11FIP1 was associated with multiple pathways. Besides, the expression of RAB11FIP1 was closely related to the infiltration levels of B cell, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. RAB11FIP1 expression in LUAD occurred with a variety of immune markers. Our findings suggest that RAB11FIP1 is related to prognosis and immune infiltrates in LUAD.

scholarly journals NRAS Expression is Associated With Prognosis and Tumor Immune Microenvironment in Lung Adenocarcinoma

2021 ◽  
Author(s):  
Yueren Yan ◽  
Zhendong Gao ◽  
Han Han ◽  
Yue Zhao ◽  
Yang Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Lung Adenocarcinoma ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Expression Level ◽  
Immune Microenvironment ◽  
Kaplan Meier ◽  
Tumor Immune Microenvironment ◽  
Cox Analysis

Abstract Purpose: NRAS plays a pivotal role in progression of various kinds of somatic malignancies; however, the correlation between NRAS and lung adenocarcinoma is less known. We aim to analyze the prognostic value of NRAS expression in lung adenocarcinoma, and explore the relationship between NRAS and tumor immune microenvironment. Methods: We obtained the transcriptome pofiles and clinical data of LUAD from The Cancer Genome Atlas database and three Genome Expression Omnibus datasets. Specimens from 325 patients with completely resected lung adenocarcinoma were collected for immunohistochemical assays of NRAS, PD-L1, PD-1 and TIM-3. Then we performed gene set enrichment analysis to investigate cancer-related and immune-related signaling pathways. TIMER algorithms were performed to evaluate tumor immune infiltrating cells and immune-related biomarkers.Results: Compared with adjacent non-tumor tissue, NRAS expression was significantly upregulated in LUAD tissue. NRAS expression was significantly correlated with more advanced stage and positive lymph nodes. Kaplan-Meier curves and Cox analysis suggested that high NRAS expression led to a poor prognosis, and could be an independent prognostic factor in LUAD patients. Besides, NRAS expression was positively correlated with CD8+ T cells, macrophages, and neutrophils, and negatively correlated with B cells and CD4+ T cells. The expression level of NRAS was positively correlated with PD-L1, PD-1, and TIM-3 both at RNA and protein level. Conclusions: To conclude, we found NRAS a novel prognostic biomarker in LUAD. Besides, the expression level of NRAS may influence the prognosis of LUAD via various kinds of cancer-related pathways and remodeling TIM.

scholarly journals EEF1A2 interacts with HSP90AB1 to promote lung adenocarcinoma metastasis via enhancing TGF-β/SMAD signalling

2021 ◽  
Author(s):  
Liqing Jia ◽  
Xiaolu Ge ◽  
Chao Du ◽  
Linna Chen ◽  
Yanhong Zhou ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Protein Interactions ◽  
Elongation Factor ◽  
Protein Translation ◽  
Protein Protein Interactions ◽  
Promising Target ◽  
Tgfβ Receptor ◽  
Mesenchymal Transformation

Abstract Background Eukaryotic protein translation elongation factor 1α2 (EEF1A2) is an oncogene that promotes the progression of breast and pancreatic cancer. In this study, we aimed to elucidate the oncogenic function of EEF1A2 in the metastasis of lung adenocarcinoma (LUAD). Methods Immunohistochemistry and western blot were used to study EEF1A2 expression levels in LUAD tissues and cells, respectively. The role of EEF1A2 in LUAD progression were investigated in vitro and in vivo. We identified potential EEF1A2-binding proteins by liquid chromatography-electrospray mass spectrometry (LC-MS)/MS. Protein–protein interactions were determined by immunofluorescence and co-immunoprecipitation (Co-IP). Results In this study, we report that EEF1A2 mediates the epithelial–mesenchymal transformation (EMT), to promote the metastasis of LUAD cells in vitro and in vivo. Moreover, EEF1A2 interacts with HSP90AB1 to increase TGFβ Receptor (TβR)-I, and TβRII expression, followed by enhanced SMAD3 and pSMAD3 expression and nuclear localisation, which promotes the EMT of LUAD cells. Overexpression of EEF1A2 in cancer tissues is associated with poor prognosis and short survival of patients with LUAD. Conclusions These findings underscore the molecular functions of EEF1A2 in LUAD metastasis and indicate that EEF1A2 represents a promising target in the treatment of aggressive LUAD.

scholarly journals Relapsed multiple myeloma demonstrates distinct patterns of immune microenvironment and malignant cell-mediated immunosuppression

2021 ◽  
Vol 11 (3) ◽  
Author(s):  
Alissa Visram ◽  
Surendra Dasari ◽  
Emilie Anderson ◽  
Shaji Kumar ◽  
Taxiarchis V. Kourelis
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
Plasma Cells ◽  
Malignant Cell ◽  
Immune Microenvironment ◽  
Cytokine Analysis ◽  
Tumor Immune Microenvironment ◽  
Early Memory ◽  
E2f Transcription Factors ◽  
Cluster 2

AbstractImmunotherapy has shown efficacy in relapsed multiple myeloma (MM). However, these therapies may depend on a functional tumor immune microenvironment (iTME) for their efficacy. Characterizing the evolution of the iTME over the disease course is necessary to optimize the timing of immunotherapies. We performed mass cytometry, cytokine analysis, and RNA sequencing on bone marrow samples from 39 (13 newly diagnosed [NDMM], 11 relapsed pre-daratumumab exposure [RMM], and 13 triple-refractory [TRMM]) MM patients. Three distinct cellular iTME clusters were identified; cluster 1 comprised mainly of NDMM and RMM patients; and clusters 2 and 3 comprised primarily of TRMM patients. We showed that naive T cells were decreased in clusters 2 and 3, cluster 2 was characterized by increased senescent T cells, and cluster 3 by decreased early memory T cells. Plasma cells in clusters 2 and 3 upregulated E2F transcription factors and MYC proliferation pathways, and downregulated interferon, TGF-beta, interleuking-6, and TNF-αlpha signaling pathways compared to cluster 1. This study suggests that the MM iTME becomes increasingly dysfunctional with therapy whereas the MM clone may be less dependent on inflammation-mediated growth pathways and less sensitive to IFN-mediated immunosurveillance. Our findings may explain the decreased sensitivity of TRMM patients to novel immunotherapies.

scholarly journals Establishment of the Prognostic Index Reflecting Tumor Immune Microenvironment of Lung Adenocarcinoma Based on Metabolism-Related Genes

2020 ◽  
Vol 11 (24) ◽  
pp. 7101-7115
Author(s):  
Jianguo Zhang ◽  
Jianzhong Zhang ◽  
Cheng Yuan ◽  
Yuan Luo ◽  
Yangyi Li ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Prognostic Index ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment

Comparing of pan-cancer tumor immune microenvironment.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15100-e15100
Author(s):  
Jiaan Ye ◽  
Longgang Cui ◽  
Xiaochen Zhao ◽  
Guanghui Lan
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Natural Killer Cell ◽  
Natural Killer ◽  
Cancer Patients ◽  
Killer Cell ◽  
Immune Microenvironment ◽  
Hepatobiliary Cancer ◽  
Tumor Immune Microenvironment ◽  
Pan Cancer

e15100 Background: Cancer treatment has entered the era of immune checkpoint inhibitors (ICI), but different tumors have different responses to ICI drugs. For example, non-small cell lung cancer and melanoma have higher response rates to ICIs than colorectal cancer and liver cancer patients. Previous studies have shown that tumor immune microenvironment have a great impact on the efficacy of ICI. Methods: This study retrospectively included pan-cancer patient specimens, using multiple fluorescent labeling immunohistochemistry to explore the differences in the immune microenvironment of different tumors. Shapiro-Wilk was used for normality test, and ANOVA or Kruskal Wallis test was used according to the results. Two-sided P < 0.05 was considered a significant difference. Results: The study included 308 patients, including 119 (38.6%) NSCLC patients, 72 (23.4%) Colorectal cancer patients, 51 (16.6%) Hepatobiliary cancer patients and 66 (21.4%) Others types of cancer patients. Among them, there was 192 (62.3%) Male, and 116 (37.7%) Female, and the median age was 57 (50-66). The proportion of CD8+ T cells and natural killer cell in tumor was statistically different. The proportion of CD8+ T cells in NSCLC, Colorectal cancer, Hepatobiliary cancer and others was 2.16%, 1%, 1.77% and 2.63%, p < 0.01; the proportion of natural killer cell was 16.44 %, 4.91%, 5.58% and 3.29%, p < 0.01. Conclusions: Different tumor types have different immune microenvironments. These results may provide valuable clues for future ICI trail design.

Can Intratumoral neutrophil lymphocyte ratio (NLR) be a prognostic biomarker in breast cancer patients?

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12573-e12573
Author(s):  
Yoshihisa Tokumaru ◽  
Masanori Oshi ◽  
Vijayashree Murthy ◽  
Eriko Katsuta ◽  
Nobuhisa Matsuhashi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Cancer Patients ◽  
Immune Cells ◽  
Breast Cancer Patients ◽  
Immune Microenvironment ◽  
High Group ◽  
Anti Cancer ◽  
Tumor Immune Microenvironment ◽  
Er Positive

e12573 Background: In breast cancer patients, it is well known that the elevation of neutrophil lymphocyte ratio (NLR) in the blood are reported to associate with poor prognosis based on the notion that neutrophils represent pro-cancer, and lymphocytes represent anti-cancer immune cells. Tumor immune microenvironment has been demonstrated to play critical roles in the outcome of breast cancer patients. However, there is scarce evidence on the clinical relevance of intratumoral NLR in breast cancer patients. In the current study, we hypothesized that intratumoral NLR high tumors are associated with worse survival particularly in TNBC that is known to have high immune cell infiltration. Methods: A total of 1904 breast cancer patients’ data from METABRIC (Molecular Taxonomy of Breast Cancer International Consortium) and analyzed. NLR was calculated by the gene expressions of CD66b (CEACAM8) and CD8 (CD8A). NLR high and low were divided by the median. Overall Survival (OS) and Disease-Free Survival were calculated utilizing Kaplan Meier method between intratumoral NLR high and low groups. xCell algorithm was used to analyze the infiltrated immune cells within the tumor immune microenvironment as we have previously published. Results: Intratumoral NLR high group was associated with worse OS in whole, ER-positive/HER2-negative, and triple negative (TN) subtypes, in agreement with the previous studies. TN subtype alone demonstrated worse DFS of NLR high group. Surprisingly, gene set enrichment analysis (GSEA) demonstrated no gene set enrichment to NLR high group, which implicates that there is no distinctive mechanism that associate with worse survival. Whereas, immune response-related gene sets significantly enriched to NLR low group in TN subtype. This enrichment was consistent in ER-positive/HER2-negative. Compared with ER-positive/HER2-negative subtype, anti-cancer immune cells such as CD4+ T cells, CD8+ T cells, M1 macrophage, and helper T helper type 1 cells were significantly infiltrated in TN patients (p < 0.001 for all genes), where M2 macrophages and neutrophils were less and regulatory T cells and T helper type 2 cells were more infiltrated in TN subtype. Furthermore, intratumoral NLR was significantly lower in TN compared with ER-positive/HER2-negative subtype (p < 0.001). These results suggest that intratumoral NLR low group is associated with better survival due to favorable tumor immune microenvironment in TN subtype rather than NLR high group has worse survival. Conclusions: Intratumoral NLR low tumor demonstrated more favorable OS and more favorable DFS in TN patients. Intratumoral NLR low breast cancer was associated with enhanced immune response and higher infiltration of anti-cancer immune cells were observed in TN subtype compared to ER-positive/HER2-negative which may contribute to the favorable outcome of in TN breast cancer.

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