scholarly journals Butyrophilin-like 9 regulates immune infiltration and serves as a prognostic marker in lung adenocarcinoma

2020 ◽  
Author(s):  
Weishuang Ma ◽  
Jiaming Liang ◽  
Siyuan Zhang ◽  
Hu Ningdong ◽  
Zisheng Chen ◽  
...  

Abstract Background: Butyrophilin (BTN) and butyrophilin-like (BTLN) belong to immunoglobulin superfamily, and also pertain the B7 co-stimulatory molecules family, which has multiple roles in immune modulation. Whether the BTNL9 expression in lung adenocarcinoma (LUAD) correlates with outcome has not been evaluated.Materials and methods: Oncomine and GEPIA were used to analyze the BTNL9, while its mRNA expression in LUAD and corresponding adjacent tissues was investigated using TIMER. The clinical prognosis of BTNL9 was assessed in the GEPIA, Kaplan-Meier plotter, and OncoLnc. Besides, the correlation between BTNL9 and tumor-infiltrating immune cells (TILs) was analyzed using TIMER and GEPIA. The correlation between BTNL9 expression and drug response was analyzed using CARE.Results: BNL9 expression was significantly low in LUAD. Low BTNL9 expression was associated with poor OS, and its expression was found to be regulated by both epigenetic regulation and post-transcriptional modification. BTNL9 expression was significant positively correlated with ImmuneScore and ESTIMATEScore. Moreover, BTNL9 expression was positively correlated with infiltrating levels of B cells, CD4+T, and macrophages, but Kaplan-Meier analysis showed that BTNL9 expression in B cells and DCs was significantly associated with OS. Furthermore, BTNL9 expression has significant positive CARE scores. Conclusions: Low BTNL9 expression can prevent the infiltration of naïve B cells and DCs in the tumor microenvironment and worsen the outcome in LUAD patients. Besides, these findings also suggest the potential role of BTNL9 as a prognostic biomarker and a new immuno-target.

2020 ◽  
Author(s):  
Weishuang Ma ◽  
Jiaming Liang ◽  
Siyuan Zhang ◽  
Hu Ningdong ◽  
Zisheng Chen ◽  
...  

Abstract Background: Butyrophilin (BTN) and butyrophilin-like (BTLN) belong to immunoglobulin superfamily, and also pertain the B7 co-stimulatory molecules family, which has multiple roles in immune modulation. Whether the BTNL9 expression in lung adenocarcinoma (LUAD) correlates with outcome has not been evaluated.Methods: Oncomine and GEPIA were used to analyze the BTNL9, while its mRNA expression in LUAD and corresponding adjacent tissues was investigated using TIMER. The clinical prognosis of BTNL9 was assessed in the GEPIA, Kaplan-Meier plotter, and OncoLnc. Besides, the correlation between BTNL9 and tumor-infiltrating immune cells (TILs) was analyzed using TIMER and GEPIA. The correlation between BTNL9 expression and drug response was analyzed using CARE.Results: BNL9 expression was significantly low in LUAD. Low BTNL9 expression was associated with poor OS, and its expression was found to be regulated by both epigenetic regulation and post-transcriptional modification. BTNL9 expression was significant positively correlated with ImmuneScore and ESTIMATEScore. Moreover, BTNL9 expression was positively correlated with infiltrating levels of B cells, CD4+T, and macrophages, but Kaplan-Meier analysis showed that BTNL9 expression in B cells and DCs was significantly associated with OS. Furthermore, BTNL9 expression has significant positive CARE scores. Conclusions: Low BTNL9 expression can prevent the infiltration of naïve B cells and DCs in the tumor microenvironment and worsen the outcome in LUAD patients. Besides, these findings also suggest the potential role of BTNL9 as a prognostic biomarker and a new immuno-target.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Weishuang Ma ◽  
Jiaming Liang ◽  
Junjian Mo ◽  
Siyuan Zhang ◽  
Ningdong Hu ◽  
...  

Abstract Background Lung adenocarcinoma (LUAD) is the most prevalent non-small cell lung cancer (NSCLC). Patients with LUAD have a poor 5-year survival rate. The use of immune checkpoint inhibitors (ICIs) for the treatment of LUAD has been on the rise in the past decade. This study explored the prognostic role of butyrophilin-like 9 (BTNL9) in LUAD. Methods Gene expression profile of buytrophilins (BTNs) was determined using the GEPIA database. The effect of BTNL9 on the survival of LUAD patients was assessed using Kaplan-Meier plotter and OncoLnc. Correlation between BTNL9 expression and tumor-infiltrating immune cells (TILs) was explored using TIMER and GEPIA databases. Further, the relationship between BTNL9 expression and drug response was evaluated using CARE. Besides, construction and evaluation of nomogram based on BTNL9 expression and TNM stage. Results BTNL9 expression was downregulated in LUAD and was associated with a poor probability of 1, 3, 5-years overall survival (OS). In addition, BTNL9 expression was regulated at epigenetic and post-transcriptional modification levels. Moreover, BTNL9 expression was significantly positively correlated with ImmuneScore and ESTIMATEScore. Furthermore, BTNL9 expression was positively associated with infiltration levels of B cells, CD4+ T cells, and macrophages. Kaplan-Meier analysis showed that BTNL9 expression in B cells and dendritic cells (DCs) was significantly associated with OS. BTNL9 expression was significantly positively correlated with CARE scores. Conclusions These findings show that BTNL9 is a potential prognostic biomarker for LUAD. Low BTNL9 expression levels associated with low infiltration levels of naïve B cells, and DCs in the tumor microenvironment are unfavorable for OS in LUAD patients.


2021 ◽  
Author(s):  
Lianxiang Luo ◽  
Manshan Li ◽  
Jiating Su ◽  
Xinyue Yao ◽  
Hui Luo

Abstract Background: FURIN, as a proprotein invertase, has been found to be expressed in a variety of cancers and plays an important role in cancer. In addition, SARS-CoV-2 requires FURIN to enter human cell. However, the role of FURIN in lung adenocarcinoma remains unclear. And the expression of SARS-CoV-2 related gene in lung adenocarcinoma have not been clarify. Methods: In this study, we obtained the expression data of Oncomine, TIMER, GEPIA, HPA. Then we used UALCAN database to analyze the expression of FURIN in different clinical feature subgroups. In PrognoScan and Kaplan-Meier plotter databases, we found a certain association between FURIN and poor OS outcomes in LUAD patients. Then we used the cBioPortal database to determine the type and frequency of FURIN changes in LUAD patients. Studies based on the TIMER database show a strong correlation between FURIN expression and various immune cell infiltrates and markers. Analysis in UALCAN database showed that the decreased promoter methylation level of FURIN in LUAD may lead to the high expression of FURIN. Furthermore, we used the LinkedOmics database to evaluate gene co-expression of FURIN in LUAD and to investigate their role in tumor immunity. Finally, we evaluated the expression of FURIN in LUAD patients who infected with SARS-CoV.Results: FURIN was highly expressed in lung adenocarcinoma. And FURIN expression was significantly associated with poor overall survival. FURIN expression was found to be correlated with six major permeable immune cells and with macrophage immune marker in LUAD patients. In addition, SARS-CoV-2 infection might affect the expression of FURIN. Conclusions: FURIN, as SARS-CoV-2 related gene, was highly expressed in LUAD. Furthermore, FURIN can be used as a promising biomarker for determining prognosis and immune infiltration in LUAD patients.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yanpeng Ding ◽  
Nuomin Liu ◽  
Mengge Chen ◽  
Yulian Xu ◽  
Sha Fang ◽  
...  

Abstract Background BLCA is a common cancer worldwide, and it is both aggressive and fatal. Immunotherapy (ICT) has achieved an excellent curative effect in BLCA; however, only some BLCA patients can benefit from ICT. MT1L is a pseudogene, and a previous study suggested that MT1L can be used as an indicator of prognosis in colorectal cancer. However, the role of MT1L in BLCA has not yet been determined. Methods Data were collected from TCGA, and logistic regression, Kaplan-Meier plotter, and multivariate Cox analysis were performed to demonstrate the correlation between the pseudogene MT1L and the prognosis of BLCA. To identify the association of MT1L with tumor-infiltrating immune cells, TIMER and TISIDB were utilized. Additionally, GSEA was performed to elucidate the potential biological function. Results The expression of MT1L was decreased in BLCA. Additionally, MT1L was positively correlated with immune cells, such as Tregs (ρ = 0.708) and MDSCs (ρ = 0.664). We also confirmed that MT1L is related to typical markers of immune cells, such as PD-1 and CTLA-4. In addition, a high MT1L expression level was associated with the advanced T and N and high grade in BLCA. Increased expression of MT1L was significantly associated with shorter OS times of BLCA patients (p < 0.05). Multivariate Cox analysis revealed that MT1L expression could be an independent prognostic factor in BLCA. Conclusion Collectively, our findings demonstrated that the pseudogene MT1L regulates the immune microenvironment, correlates with poor survival, and is an independent prognostic biomarker in BLCA.


2018 ◽  
Vol 38 (4) ◽  
pp. 1031-1038 ◽  
Author(s):  
Li Jin ◽  
Xuan Fang ◽  
Chao Dai ◽  
Nan Xiang ◽  
Jinhui Tao ◽  
...  

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yang-Jie Wu ◽  
Ai-Tao Nai ◽  
Gui-Cheng He ◽  
Fei Xiao ◽  
Zhi-Min Li ◽  
...  

Abstract Background Dihydropyrimidinase like 2 (DPYSL2) has been linked to tumor metastasis. However, the function of DPSY2L in lung adenocarcinoma (LUAD) is yet to be explored. Methods Herein, we assessed DPYSL2 expression in various tumor types via online databases such as Oncomine and Tumor Immune Estimation Resource (TIMER). Further, we verified the low protein and mRNA expressions of DPYSL2 in LUAD via the ULCAN, The TCGA and GEPIA databases. We applied the ROC curve to examine the role of DPYSL2 in diagnosis. The prognostic significance of DPYSL2 was established through the Kaplan–Meier plotter and the Cox analyses (univariate and multivariate). TIMER was used to explore DPYSL2 expression and its connection to immune infiltrated cells. Through Gene Set Enrichment Analysis, the possible mechanism of DPYSL2 in LUAD was investigated. Results In this study, database analysis revealed lower DPYSL2 expression in LUAD than in normal tissues. The ROC curve suggested that expression of DPYSL2 had high diagnostic efficiency in LUAD. The DPYSL2 expression had an association with the survival time of LUAD patients in the Kaplan–Meier plotter and the Cox analyses. The results from TIMER depicted a markedly positive correlation of DPYSL2 expression with immune cells infiltrated in LUAD, such as macrophages, dendritic cells, CD4+ T cells, and neutrophils. Additionally, many gene markers for the immune system had similar positive correlations in the TIMER analysis. In Gene Set Enrichment Analysis, six immune-related signaling pathways were associated with DPYSL2. Conclusions In summary, DPYSL2 is a novel biomarker with diagnostic and prognostic potential for LUAD as well as an immunotherapy target. Highlights Expression of DPYSL2 was considerably lower in LUAD than in normal tissues. Investigation of multiple databases showed a high diagnostic value of DPYSL2 in LUAD. DPYSL2 can independently predict the LUAD outcomes. Immune-related mechanisms may be potential ways for DPYSL2 to play a role in LUAD.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Bernardino Clavo ◽  
Norberto Santana-Rodríguez ◽  
Pedro Llontop ◽  
Dominga Gutiérrez ◽  
Gerardo Suárez ◽  
...  

Introduction. This article provides an overview of the potential use of ozone as an adjuvant during cancer treatment.Methods. We summarize the findings of the most relevant publications focused on this goal, and we include our related clinical experience.Results. Over several decades, prestigious journals have publishedin vitrostudies on the capacity of ozone to induce direct damage on tumor cells and, as well, to enhance the effects of radiotherapy and chemotherapy. Indirect effects have been demonstrated in animal models: immune modulation by ozone alone and sensitizing effect of radiotherapy by concurrent ozone administration. The effects of ozone in modifying hemoglobin dissociation curve, 2,3-diphosphoglycerate levels, locoregional blood flow, and tumor hypoxia provide additional support for potential beneficial effects during cancer treatment. Unfortunately, only a few clinical studies are available. Finally, we describe some works and our experience supporting the potential role of local ozone therapy in treating delayed healing after tumor resection, to avoid delays in commencing radiotherapy and chemotherapy.Conclusions.In vitroand animal studies, as well as isolated clinical reports, suggest the potential role of ozone as an adjuvant during radiotherapy and/or chemotherapy. However, further research, such as randomized clinical trials, is required to demonstrate its potential usefulness as an adjuvant therapeutic tool.


2020 ◽  
Vol 19 ◽  
pp. 153303382097754
Author(s):  
Rongchang Zhao ◽  
Dan Ding ◽  
Wenyan Yu ◽  
Chunrong Zhu ◽  
Yan Ding

Background: As a common pathological type of lung cancer, lung adenocarcinoma (LUAD) is mainly treated by surgery, chemotherapy, targeted therapy and radiotherapy. Although a relatively mature treatment system has been established, there are few studies on the microenvironment of LUAD. Material and Methods: The immune and stromal scores of patients from the LUAD cohort in the TCGA database were obtained by using ESTIMATE. The relationship of immune and stromal scores with the clinicopathological characteristics and overall survival of LUAD patients was assessed by R. GO, KEGG and Cox regression analyses were employed to analyze intersecting genes and to identify reliable prognostic markers. The identified genes were also analyzed in the GEPIA database to assess their correlations with survival, and these relationships were verified with the Kaplan-Meier Plotter database. Results: The immune score was related to the survival time and tumor topography of LUAD patients. There was a significant correlation between stromal score and tumor metastasis. Through multivariate analysis, stage (HR = 1.640, 95% CI = 1.019-2.642, P = 0.042) and risk score (HR = 1.036, 95% CI = 1.026-1.046, P < 0.001). The genes (ARHGAP15, BTLA, CASS4, CLECL1, FAM129C, STAP1, TESPA1, and S100P) showed credible prognostic value in LUAD patients in TCGA through GEPIA database online analysis and verification in the Kaplan-Meier plotter database. Conclusions: In the microenvironment of lung adenocarcinoma, the differentially expressed genes screened by immune score and stromal score have certain value in evaluating the survival/prognosis of patients, as well as the invasion and progression of tumors.


2007 ◽  
Vol 22 (5) ◽  
pp. 462-465 ◽  
Author(s):  
Rosalind M. Harrison

AbstractIntroduction:Increasingly, disasters and disaster response have become prominent issues in recent years. Despite their involvement, there have been almost no investigations into the roles of physiotherapists in emergency disaster responses.Additionally, physiotherapists are not employed in emergency disaster response by many of the principal non-governmental organizations supplying such care, although they are included in military responses in the United States and United Kingdom, and in Disaster Medical Assistance Teams in the US.This paper, based on a small qualitative study, focuses on the potential role and nature of input of physiotherapists in disaster response.Methods:A qualitative approach was chosen due to the emergent nature of the phenomenon. Four physiotherapists, all of whom had been involved in some type of disaster response, agreed to participate. Semi-structured telephone interviews were used to explore participants' experiences following disaster response, and to gain ideas about future roles for physiotherapists. Interviews were recorded, transcribed, and later analyzed using coding and categorization of data.Results:Four main themes emerged: (1) descriptions of disasters; (2) current roles of the physiotherapist; (3) future roles of physiotherapists; and (4) overcoming barriers. Although all four physiotherapists had been ill-prepared for disaster response, they took on multiple roles, primarily in organization and treatment. However, participants identified several barriers to future involvement, including organizational and professional barriers, and gave suggestions for overcoming these.Conclusions:The participants had participated in disaster response, but in ill-defined roles, indicating a need for a greater understanding of disaster response among the physiotherapy community and by organizations supplying such care. The findings of this study have implications for such organizations in terms of employing skilled physiotherapists in order to improve disaster response. In future disasters, physiotherapy will be of benefit in treating and preventing rescue worker injury and treating musculoskeletal, critical, respiratory, and burn patients.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21017-e21017
Author(s):  
Jinchun Wu ◽  
Xianyu Liu ◽  
Yanhua Mou ◽  
Shan Zeng ◽  
Jin Zhang ◽  
...  

e21017 Background: Lung adenocarcinoma (LUAD) occupies the most of non-small cell lung cancer (NSCLC) and shows promising response to PD-1 immunotherapy, but immune escape will cause treatment failure indicating poor prognosis. TWEAK (Tumor necrosis factor-related weak inducer of apoptosis, also known as TNFSF12) combining with its receptor FN14 (fibroblast growth factor–inducible 14) mediates crucial innate and adaptive immune pathways to promote the progression of multiple autoimmune diseases. So we assumed that TWEAK is a prognostic predictor and related with tumor-infiltrating immune cells (TIICs) in LUAD. Methods: TWEAK expression of LUAD was primarily investigated in The Cancer Immunome Atlas (TCIA) and then validated in Tumor Immune Estimation Resource (TIMER) databases. We assessed the effect of TWEAK on the survival via the Kaplan-Meier plotter, GEPIA2 (gene expression profiling interactive analysis) and PrognoScan databases. The relation between TWEAK and TIICs was explored in TIMER and TCIA, as well as the correlation of TWEAK and FN14 was analyzed in TIMER and GEPIA2. Results: Low TWEAK expression was significantly associated with poor relapse-free survival (RFS) (HR = 0.62, 95% CI = 0.4~0.97, logrank P = 0.035) and overall survival (OS) (HR = 0.61, 95% CI = 0.46~0.83, logrank P = 0.0012) in LUAD from Kaplan-Meier plotter. Similar impacts of TWEAK on the survival were validated in GEPIA2 and four independent cohorts from PrognoScan (jacob-00182-CANDF, GSE13213, jacob-00182-MSK and GSE31210). Moreover, reduced TWEAK expression was closely related with the paucity of TIICs which contributed to poor OS, including central memory CD8 T cells, plasmacytoid dendritic cells, activated CD8 T cells, monocytes, T follicular helper cells, immature B cells and eosinophils. In addition, TWEAK expression was positively related with the expression level of FN14 in both GEPIA2(R = 0.13, P= 0.0031) and TIMER (partial.cor = 0.212, P= 2.04e-06). Conclusions: Low TWEAK expression maybe indicate poor prognosis in LUAD, and correlated with the impaired infiltration of immune cells in the tumor region. The defective TWEAK/FN14 pathway possibly accounts for these observations, but the underlying mechanism needs to be further explored.


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