scholarly journals Bioinformatics Analyses Reveals a Comprehensive Landscape of CXC Chemokine Family Functions in Non-Small Cell Lung Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-34
Author(s):  
He Tian ◽  
Liyu Wang ◽  
Yu Liu ◽  
Yalong Wang ◽  
Yujia Zheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Expression Levels ◽  
Cxc Chemokine ◽  
Pathological Stages ◽  
Chemokine Family

Backgrounds. Lung cancer is a major source of tumor-related death each year with non-small cell lung cancer (NSCLC) being a prevalent subtype. The metastasis from NSCLC to the brain usually imposes many neuron disorders. Previous studies have suggested that communications among cancer cells and interstitial cells are essential in tumorigenesis and are influenced by chemokines. In the tumor microenvironment, CXC chemokines can participate in the shifting of immune cells and manage tumor cell condition, thus affecting the progression of cancer and patient destinies. However, the expression and values of CXC chemokine family in NSCLC have not been systematically illustrated using public databases. Methods. UALCAN, STRING, ONCOMINE, GeneMANIA, cBioPortal, GEPIA, TISIDB, TRRUST, TIMER, Kaplan-Meier Plotter, and R software were utilized in this study. Results. Based on the TIMER and UACLCAN databases, in LUAD patients, the expression levels of CXCL10, CXCL13, and CXCL14 were significantly elevated while the transcriptional levels of CXCL2/3/4/7/12/16 were significantly reduced; in LUSC patients, the expression levels of CXCL6/10/13/14 were significantly elevated while the expression levels of CXCL2/3/4/5/7/11/12/16/17 were significantly reduced. We found remarkable relevance between the pathological stages of LUAD patients and the expressions of CXCL8 (positive) and CXCL17 (negative). Similarly, there are significant correlations between the pathological stages of LUSC patients and the expressions of CXCL1/2/6/17. In LUAD, patients with low expression levels of CXCL1/4/7/8 and patients with high expression levels of CXCL12/14/16 were associated with a significantly better prognosis. But in LUSC, all correlations between chemokines and prognosis are statistically insignificant. Pairwise expression correlation analysis among CXC chemokines shows that there are 7 significant correlations (between CXCL1 and CXCL2, between CXCL1 and CXCL3, between CXCL1 and CXCL8, between CXCL2 and CXCL3, between CXCL4 and CXCL7, between CXCL9 and CXCL10, and between CXCL9 and CXCL11) in LUAD and 4 significant correlations (between CXCL1 and CXCL8, between CXCL2 and CXCL3, between CXCL4 and CXCL7, and between CXCL10 and CXCL11) in LUSC. Significant correlations between the expressions of CXC chemokines and the infiltration of six common types of immune cells were also discovered in both LUAD and LUSC. Conclusions. We provided a comprehensive landscape of the CXC chemokine family in LUAD and LUSC using the bioinformatics method and found differences between LUSC and LUAD in the field of CXC chemokines. Our study may help validate and identify known novel immunotherapeutic targets and prognostic biomarkers.

lncRNAs as Potential Targets in Small Cell Lung Cancer: MYC -dependent Regulation

2020 ◽  
Vol 20 (17) ◽  
pp. 2074-2081
Author(s):  
Onur Tokgun ◽  
Pervin E. Tokgun ◽  
Kubilay Inci ◽  
Hakan Akca
Keyword(s):  
Lung Cancer ◽  
Stem Cell ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Therapeutic Strategy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Expression Levels ◽  
Qrt Pcr ◽  
Shrna Vector

Background: Small Cell Lung Cancer (SCLC) is a highly aggressive malignancy. MYC family oncogenes are amplified and overexpressed in 20% of SCLCs, showing that MYC oncogenes and MYC regulated genes are strong candidates as therapeutic targets for SCLC. c-MYC plays a fundamental role in cancer stem cell properties and malignant transformation. Several targets have been identified by the activation/repression of MYC. Deregulated expression levels of lncRNAs have also been observed in many cancers. Objective: The aim of the present study is to investigate the lncRNA profiles which depend on MYC expression levels in SCLC. Methods: Firstly, we constructed lentiviral vectors for MYC overexpression/inhibition. MYC expression is suppressed by lentiviral shRNA vector in MYC amplified H82 and N417 cells, and overexpressed by lentiviral inducible overexpression vector in MYC non-amplified H345 cells. LncRNA cDNA is transcribed from total RNA samples, and 91 lncRNAs are evaluated by qRT-PCR. Results: We observed that N417, H82 and H345 cells require MYC for their growth. Besides, MYC is not only found to regulate the expressions of genes related to invasion, stem cell properties, apoptosis and cell cycle (p21, Bcl2, cyclinD1, Sox2, Aldh1a1, and N-Cadherin), but also found to regulate lncRNAs. With this respect, expressions of AK23948, ANRIL, E2F4AS, GAS5, MEG3, H19, L1PA16, SFMBT2, ZEB2NAT, HOTAIR, Sox2OT, PVT1, and BC200 were observed to be in parallel with MYC expression, whereas expressions of Malat1, PTENP1, Neat1, UCA1, SNHG3, and SNHG6 were inversely correlated. Conclusion: Targeting MYC-regulated genes as a therapeutic strategy can be important for SCLC therapy. This study indicated the importance of identifying MYC-regulated lncRNAs and that these can be utilized to develop a therapeutic strategy for SCLC.

scholarly journals P2.01-040 CXC Chemokine Receptor 3 and ELR Motif Negative CXC Chemokine Ligand Axis in Non-Small Cell Lung Cancer

2017 ◽  
Vol 12 (1) ◽  
pp. S809-S810
Author(s):  
Artjoms Spaks ◽  
Donats Breiva ◽  
Ilmars Tracums ◽  
Anastasija Bistrova ◽  
Krista Grigorovica ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Chemokine Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cxc Chemokine ◽  
Chemokine Ligand

scholarly journals Natural Killer Cells and Dendritic Cells: Expanding Clinical Relevance in the Non-Small Cell Lung Cancer (NSCLC) Tumor Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4037
Author(s):  
Pankaj Ahluwalia ◽  
Meenakshi Ahluwalia ◽  
Ashis K. Mondal ◽  
Nikhil S. Sahajpal ◽  
Vamsi Kota ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dendritic Cells ◽  
Tumor Microenvironment ◽  
Small Cell Lung Cancer ◽  
Nk Cells ◽  
Natural Killer ◽  
Cell Lung Cancer ◽  
Immune Cells ◽  
Small Cell ◽  
Small Cell Lung

Non-small cell lung cancer (NSCLC) is a major subtype of lung cancer that accounts for almost 85% of lung cancer cases worldwide. Although recent advances in chemotherapy, radiotherapy, and immunotherapy have helped in the clinical management of these patients, the survival rate in advanced stages remains dismal. Furthermore, there is a critical lack of accurate prognostic and stratification markers for emerging immunotherapies. To harness immune response modalities for therapeutic benefits, a detailed understanding of the immune cells in the complex tumor microenvironment (TME) is required. Among the diverse immune cells, natural killer (NK cells) and dendritic cells (DCs) have generated tremendous interest in the scientific community. NK cells play a critical role in tumor immunosurveillance by directly killing malignant cells. DCs link innate and adaptive immune systems by cross-presenting the antigens to T cells. The presence of an immunosuppressive milieu in tumors can lead to inactivation and poor functioning of NK cells and DCs, which results in an adverse outcome for many cancer patients, including those with NSCLC. Recently, clinical intervention using modified NK cells and DCs have shown encouraging response in advanced NSCLC patients. Herein, we will discuss prognostic and predictive aspects of NK cells and DC cells with an emphasis on NSCLC. Additionally, the discussion will extend to potential strategies that seek to enhance the anti-tumor functionality of NK cells and DCs.

scholarly journals Ectonucleotidase CD39 and Checkpoint Signalling Receptor Programmed Death 1 are Highly Elevated in Intratumoral Immune Cells in Non–small-cell Lung Cancer

2020 ◽  
Vol 13 (1) ◽  
pp. 17-24 ◽  
Author(s):  
Anders Tøndell ◽  
Sissel Gyrid Freim Wahl ◽  
Anne-Marit Sponaas ◽  
Sveinung Sørhaug ◽  
Magne Børset ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Programmed Death ◽  
Programmed Death 1

scholarly journals Circ_MDM2_000139, Circ_ATF2_001418, Circ_CDC25C_002079, and Circ_BIRC6_001271 Are Involved in the Functions of XAV939 in Non-Small Cell Lung Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Haixiang Yu ◽  
Lei Xu ◽  
Zhengjia Liu ◽  
Bo Guo ◽  
Zhifeng Han ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Regulatory Network ◽  
Family Members ◽  
Enrichment Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Expression Levels ◽  
Relative Expression

Background. The small molecule inhibitor XAV939 could inhibit the proliferation and promote the apoptosis of non-small cell lung cancer (NSCLC) cells. This study was conducted to identify the key circular RNAs (circRNAs) and microRNAs (miRNAs) in XAV939-treated NSCLC cells. Methods. After grouping, the NCL-H1299 cells in the treatment group were treated by 10 μM XAV939 for 12 h. RNA-sequencing was performed, and then the differentially expressed circRNAs (DE-circRNAs) were analyzed by the edgeR package. Using the clusterprofiler package, enrichment analysis for the hosting genes of the DE-circRNAs was performed. Using Cytoscape software, the miRNA-circRNA regulatory network was built for the disease-associated miRNAs and the DE-circRNAs. The DE-circRNAs that could translate into proteins were predicted using circBank database and IRESfinder tool. Finally, the transcription factor (TF)-circRNA regulatory network was built by Cytoscape software. In addition, A549 and HCC-827 cell treatment with XAV939 were used to verify the relative expression levels of key DE-circRNAs. Results. There were 106 DE-circRNAs (including 61 upregulated circRNAs and 45 downregulated circRNAs) between treatment and control groups. Enrichment analysis for the hosting genes of the DE-circRNAs showed that ATF2 was enriched in the TNF signaling pathway. Disease association analysis indicated that 8 circRNAs (including circ_MDM2_000139, circ_ATF2_001418, circ_CDC25C_002079, and circ_BIRC6_001271) were correlated with NSCLC. In the miRNA-circRNA regulatory network, let-7 family members⟶circ_MDM2_000139, miR-16-5p/miR-134-5p⟶circ_ATF2_001418, miR-133b⟶circ_BIRC6_001271, and miR-221-3p/miR-222-3p⟶circ_CDC25C_002079 regulatory pairs were involved. A total of 47 DE-circRNAs could translate into proteins. Additionally, circ_MDM2_000139 was targeted by the TF POLR2A. The verification test showed that the relative expression levels of circ_MDM2_000139, circ_CDC25C_002079, circ_ATF2_001418, and circ_DICER1_000834 in A549 and HCC-827 cell treatment with XAV939 were downregulated comparing with the control. Conclusions. Let-7 family members and POLR2A targeting circ_MDM2_000139, miR-16-5p/miR-134-5p targeting circ_ATF2_001418, miR-133b targeting circ_BIRC6_001271, and miR-221-3p/miR-222-3p targeting circ_CDC25C_002079 might be related to the mechanism in the treatment of NSCLC by XAV939.

scholarly journals Overexpressed C14orf166 associates with disease progression and poor prognosis in non-small-cell lung cancer

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Yan-Wu Zhou ◽  
Rong Li ◽  
Chao-Jun Duan ◽  
Yang Gao ◽  
Yuan-Da Cheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Disease Progression ◽  
Cell Lung Cancer ◽  
Prognostic Significance ◽  
Small Cell ◽  
Mrna Levels ◽  
Small Cell Lung ◽  
Expression Levels ◽  
Normal Tissues

Chromosome 14 ORF 166 (C14orf166), a protein involved in the regulation of RNA transcription and translation, has been reported to possess the potency to promote tumorigenesis; however, the role of C14orf166 in non-small-cell lung cancer (NSCLC) remains unknown. The purpose of the present study was to assess C14orf166 expression and its clinical significance in NSCLC. Immunohistochemical staining, quantitative real-time PCR (qRT-PCR), and Western blotting were used to detect the C14orf166 protein and mRNA expression levels in NSCLC tissues compared with adjacent normal tissues, as well as in NSCLC cells lines compared with normal human bronchial epithelial cells (HBE). Then, the correlations between the C14orf166 expression levels and the clinicopathological features of NSCLC were analyzed. Additionally, the Cox proportional hazard model was used to evaluate the prognostic significance of C14orf166. We found that C14orf166 expression increased in carcinoma tissues compared with their adjacent normal tissues at the protein (P<0.001) and mRNA levels (P<0.001). High expression of C14orf166 was significantly associated with the T stage (P=0.006), lymph node metastasis (P=0.001), advanced TNM stage (P<0.001), and chemotherapy (P<0.001). Moreover, according to the survival analysis, patients with overexpressed C14orf166 were inclined to experience a shorter overall survival and disease-free survival time (P<0.001). Multivariate COX analysis implied that C14orf166 was an independent prognostic biomarker. Taken together, our findings indicate that the overexpression of C14orf166 may contribute to the disease progression of NSCLC, represent a novel prognostic predictor and help high-risk patients make better decisions for subsequent therapy.

Tumor expression levels of CSC markers in resectable non-small cell lung cancer.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 7562-7562 ◽  
Author(s):  
Silvia Calabuig ◽  
Eloisa Jantus-Lewintre ◽  
Rut Lucas ◽  
Rosa Farras ◽  
Marta Usó ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Expression Levels ◽  
Tumor Expression
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